PACSAB: Coarse-Grained Force Field for the Study of Protein-Protein Interactions and Conformational Sampling in Multiprotein Systems.

PubMed

Emperador, Agustí; Sfriso, Pedro; Villarreal, Marcos Ariel; Gelpí, Josep Lluis; Orozco, Modesto

2015-12-08

Molecular dynamics simulations of proteins are usually performed on a single molecule, and coarse-grained protein models are calibrated using single-molecule simulations, therefore ignoring intermolecular interactions. We present here a new coarse-grained force field for the study of many protein systems. The force field, which is implemented in the context of the discrete molecular dynamics algorithm, is able to reproduce the properties of folded and unfolded proteins, in both isolation, complexed forming well-defined quaternary structures, or aggregated, thanks to its proper evaluation of protein-protein interactions. The accuracy and computational efficiency of the method makes it a universal tool for the study of the structure, dynamics, and association/dissociation of proteins.

Adsorbed molecules in external fields: Effect of confining potential.

PubMed

Tyagi, Ashish; Silotia, Poonam; Maan, Anjali; Prasad, Vinod

2016-12-05

We study the rotational excitation of a molecule adsorbed on a surface. As is well known the interaction potential between the surface and the molecule can be modeled in number of ways, depending on the molecular structure and the geometry under which the molecule is being adsorbed by the surface. We explore the effect of change of confining potential on the excitation, which is largely controlled by the static electric fields and continuous wave laser fields. We focus on dipolar molecules and hence we restrict ourselves to the first order interaction in field-molecule interaction potential either through permanent dipole moment or/and the molecular polarizability parameter. It is shown that confining potential shapes, strength of the confinement, strongly affect the excitation. We compare our results for different confining potentials. Copyright © 2016 Elsevier B.V. All rights reserved.

An implicit divalent counterion force field for RNA molecular dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henke, Paul S.; Mak, Chi H., E-mail: cmak@usc.edu; Center of Applied Mathematical Sciences, University of Southern California, Los Angeles, California 90089

How to properly account for polyvalent counterions in a molecular dynamics simulation of polyelectrolytes such as nucleic acids remains an open question. Not only do counterions such as Mg{sup 2+} screen electrostatic interactions, they also produce attractive intrachain interactions that stabilize secondary and tertiary structures. Here, we show how a simple force field derived from a recently reported implicit counterion model can be integrated into a molecular dynamics simulation for RNAs to realistically reproduce key structural details of both single-stranded and base-paired RNA constructs. This divalent counterion model is computationally efficient. It works with existing atomistic force fields, or coarse-grainedmore » models may be tuned to work with it. We provide optimized parameters for a coarse-grained RNA model that takes advantage of this new counterion force field. Using the new model, we illustrate how the structural flexibility of RNA two-way junctions is modified under different salt conditions.« less

Cellular and molecular pathways of extremely-low-frequency electromagnetic field interactions with living systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tenforde, T.S.

1992-06-01

There is growing evidence that environmental electric and magnetic fields in the extremely-low-frequency (ELF) band below 300 Hz can influence biological functions by mechanisms that are only poorly understood at the present time. The primary objectives of this paper are to review the physical properties of ELF fields, their interactions with living systems at the tissue, cellular, and subcellular levels, and the key role of cell membranes ;in the transduction of signals from imposed ELF fields. Topics of discussion include signal-to-noise ratios for single cells and cell aggregates, resonance phenomena involving a combination of static and ELF magnetic fields, andmore » the possible influence of ELF fields on molecular signaling pathways that involve membrane receptors and cytoplasmic second messengers.« less

Ultrafast dynamics induced by the interaction of molecules with electromagnetic fields: Several quantum, semiclassical, and classical approaches.

PubMed

Antipov, Sergey V; Bhattacharyya, Swarnendu; El Hage, Krystel; Xu, Zhen-Hao; Meuwly, Markus; Rothlisberger, Ursula; Vaníček, Jiří

2017-11-01

Several strategies for simulating the ultrafast dynamics of molecules induced by interactions with electromagnetic fields are presented. After a brief overview of the theory of molecule-field interaction, we present several representative examples of quantum, semiclassical, and classical approaches to describe the ultrafast molecular dynamics, including the multiconfiguration time-dependent Hartree method, Bohmian dynamics, local control theory, semiclassical thawed Gaussian approximation, phase averaging, dephasing representation, molecular mechanics with proton transfer, and multipolar force fields. In addition to the general overview, some focus is given to the description of nuclear quantum effects and to the direct dynamics, in which the ab initio energies and forces acting on the nuclei are evaluated on the fly. Several practical applications, performed within the framework of the Swiss National Center of Competence in Research "Molecular Ultrafast Science and Technology," are presented: These include Bohmian dynamics description of the collision of H with H 2 , local control theory applied to the photoinduced ultrafast intramolecular proton transfer, semiclassical evaluation of vibrationally resolved electronic absorption, emission, photoelectron, and time-resolved stimulated emission spectra, infrared spectroscopy of H-bonding systems, and multipolar force fields applications in the condensed phase.

Ultrafast dynamics induced by the interaction of molecules with electromagnetic fields: Several quantum, semiclassical, and classical approaches

PubMed Central

Antipov, Sergey V.; Bhattacharyya, Swarnendu; El Hage, Krystel; Xu, Zhen-Hao; Meuwly, Markus; Rothlisberger, Ursula; Vaníček, Jiří

2018-01-01

Several strategies for simulating the ultrafast dynamics of molecules induced by interactions with electromagnetic fields are presented. After a brief overview of the theory of molecule-field interaction, we present several representative examples of quantum, semiclassical, and classical approaches to describe the ultrafast molecular dynamics, including the multiconfiguration time-dependent Hartree method, Bohmian dynamics, local control theory, semiclassical thawed Gaussian approximation, phase averaging, dephasing representation, molecular mechanics with proton transfer, and multipolar force fields. In addition to the general overview, some focus is given to the description of nuclear quantum effects and to the direct dynamics, in which the ab initio energies and forces acting on the nuclei are evaluated on the fly. Several practical applications, performed within the framework of the Swiss National Center of Competence in Research “Molecular Ultrafast Science and Technology,” are presented: These include Bohmian dynamics description of the collision of H with H2, local control theory applied to the photoinduced ultrafast intramolecular proton transfer, semiclassical evaluation of vibrationally resolved electronic absorption, emission, photoelectron, and time-resolved stimulated emission spectra, infrared spectroscopy of H-bonding systems, and multipolar force fields applications in the condensed phase. PMID:29376107

Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model.

PubMed

Mohebifar, Mohamad; Johnson, Erin R; Rowley, Christopher N

2017-12-12

London dispersion interactions play an integral role in materials science and biophysics. Force fields for atomistic molecular simulations typically represent dispersion interactions by the 12-6 Lennard-Jones potential using empirically determined parameters. These parameters are generally underdetermined, and there is no straightforward way to test if they are physically realistic. Alternatively, the exchange-hole dipole moment (XDM) model from density-functional theory predicts atomic and molecular London dispersion coefficients from first principles, providing an innovative strategy to validate the dispersion terms of molecular-mechanical force fields. In this work, the XDM model was used to obtain the London dispersion coefficients of 88 organic molecules relevant to biochemistry and pharmaceutical chemistry and the values compared with those derived from the Lennard-Jones parameters of the CGenFF, GAFF, OPLS, and Drude polarizable force fields. The molecular dispersion coefficients for the CGenFF, GAFF, and OPLS models are systematically higher than the XDM-calculated values by a factor of roughly 1.5, likely due to neglect of higher order dispersion terms and premature truncation of the dispersion-energy summation. The XDM dispersion coefficients span a large range for some molecular-mechanical atom types, suggesting an unrecognized source of error in force-field models, which assume that atoms of the same type have the same dispersion interactions. Agreement with the XDM dispersion coefficients is even poorer for the Drude polarizable force field. Popular water models were also examined, and TIP3P was found to have dispersion coefficients similar to the experimental and XDM references, although other models employ anomalously high values. Finally, XDM-derived dispersion coefficients were used to parametrize molecular-mechanical force fields for five liquids-benzene, toluene, cyclohexane, n-pentane, and n-hexane-which resulted in improved accuracy in the computed enthalpies of vaporization despite only having to evaluate a much smaller section of the parameter space.

Use of Molecular Modeling to Determine the Interaction and Competition of Gases within Coal for Carbon Dioxide Sequestration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeffrey D. Evanseck; Jeffry D. Madura

A 3-dimensional coal structural model for the Argonne Premium Coal Pocahontas No. 3 has been generated. The model was constructed based on the wealth of structural information available in the literature with the enhancement that the structural diversity within the structure was represented implicitly (for the first time) based on image analysis of HRTEM in combination with LDMS data. The complex and large structural model (>10,000 carbon atoms) will serve as a basis for examining the interaction of gases within this low volatile bituminous coal. Simulations are of interest to permit reasonable simulations of the host-guest interactions with regard tomore » carbon dioxide sequestration within coal and methane displacement from coal. The molecular structure will also prove useful in examining other coal related behavior such as solvent swelling, liquefaction and other properties. Molecular models of CO{sub 2} have been evaluated with water to analyze which classical molecular force-field parameters are the most reasonable to predict the interactions of CO{sub 2} with water. The comparison of the molecular force field models was for a single CO{sub 2}-H{sub 2}O complex and was compared against first principles quantum mechanical calculations. The interaction energies and the electrostatic interaction distances were used as criteria in the comparison. The ab initio calculations included Hartree-Fock, B3LYP, and Moeller-Plesset 2nd, 3rd, and 4th order perturbation theories with basis sets up to the aug-cc-pvtz basis set. The Steele model was the best literature model, when compared to the ab initio data, however, our new CO{sub 2} model reproduces the QM data significantly better than the Steele force-field model.« less

The 1-ethyl-3-methylimidazolium bis(trifluoro-methylsulfonyl)-imide ionic liquid nanodroplets on solid surfaces and in electric field: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Dong, Dengpan; Vatamanu, Jenel P.; Wei, Xiaoyu; Bedrov, Dmitry

2018-05-01

Atomistic molecular dynamics simulations were conducted to study the wetting states of 1-ethyl-3-methylimidazolium bis(trifluoro-methylsulfonyl)-imide ionic liquid (IL) nanodroplets on surfaces with different strengths of van der Waals (VDW) interactions and in the presence of an electric field. By adjusting the depth of Lennard-Jones potential, the van der Waals interaction between the solid surface and ionic liquid was systematically varied. The shape of the droplets was analyzed to extract the corresponding contact angle utilized to characterize wetting states of the nanodroplets. The explored range of surface-IL interactions allowed contact angles ranging from complete IL spreading on the surface to poor wettability. The effect of the external electrical field was explored by adding point charges to the surface atoms. Systems with two charge densities (±0.002 e/atom and ±0.004 e/atom) that correspond to 1.36 V/nm and 2.72 V/nm electric fields were investigated. Asymmetrical wetting states were observed for both cases. At 1.36 V/nm electric field, contributions of IL-surface VDW interactions and Coulombic interactions to the wetting state were competitive. At 2.72 V/nm field, electrostatic interactions dominate the interaction between the nanodroplet and surface, leading to enhanced wettability on all surfaces.

L. V. Keldysh’s “Ionization in the Field of a Strong Electromagnetic Wave” and modern physics of atomic interaction with a strong laser field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fedorov, M. V., E-mail: fedorov@gmail.com

2016-03-15

Basic premises, approximations, and results of L.V. Keldysh’s 1964 work on multiphoton ionization of atoms are discussed, as well as its influence on the modern science of the interaction of atomic–molecular systems with a strong laser field.

Molecular modeling studies of interactions between sodium polyacrylate polymer and calcite surface

NASA Astrophysics Data System (ADS)

Ylikantola, A.; Linnanto, J.; Knuutinen, J.; Oravilahti, A.; Toivakka, M.

2013-07-01

The interactions between calcite pigment and sodium polyacrylate dispersing agent, widely used in papermaking as paper coating components, were investigated using classical force field and quantum chemical approaches. The objective was to understand interactions between the calcite surface and sodium polyacrylate polymer at 300 K using molecular dynamics simulations. A quantum mechanical ab initio Hartree-Fock method was also used to obtain detailed information about the sodium polyacrylate polymer structure. The effect of water molecules (moisture) on the interactions was also examined. Calculations showed that molecular weight, branching and the orientation of sodium polyacrylate polymers influence the interactions between the calcite surface and the polymer. The force field applied, and also water molecules, were found to have an impact on all systems studied. Ab initio Hartree-Fock calculations indicated that there are two types of coordination between sodium atoms and carboxylate groups of the sodium polyacrylate polymer, inter- and intra-carboxylate group coordination. In addition, ab initio Hartree-Fock calculations of the structure of the sodium polyacrylate polymer produced important information regarding interactions between the polymers and carboxylated styrene-butadiene latex particles.

Fungal innate immunity induced by bacterial microbe-associated molecular patterns (MAMPs)

USDA-ARS?s Scientific Manuscript database

Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal-bacterial interaction at the molecular level is still in its infancy and very little is known about fungal molecular responses to bacteria, a...

Amino acid analogues bind to carbon nanotube via π-π interactions: Comparison of molecular mechanical and quantum mechanical calculations

NASA Astrophysics Data System (ADS)

Yang, Zaixing; Wang, Zhigang; Tian, Xingling; Xiu, Peng; Zhou, Ruhong

2012-01-01

Understanding the interaction between carbon nanotubes (CNTs) and biomolecules is essential to the CNT-based nanotechnology and biotechnology. Some recent experiments have suggested that the π-π stacking interactions between protein's aromatic residues and CNTs might play a key role in their binding, which raises interest in large scale modeling of protein-CNT complexes and associated π-π interactions at atomic detail. However, there is concern on the accuracy of classical fixed-charge molecular force fields due to their classical treatments and lack of polarizability. Here, we study the binding of three aromatic residue analogues (mimicking phenylalanine, tyrosine, and tryptophan) and benzene to a single-walled CNT, and compare the molecular mechanical (MM) calculations using three popular fixed-charge force fields (OPLSAA, AMBER, and CHARMM), with quantum mechanical (QM) calculations using the density-functional tight-binding method with the inclusion of dispersion correction (DFTB-D). Two typical configurations commonly found in π-π interactions are used, one with the aromatic rings parallel to the CNT surface (flat), and the other perpendicular (edge). Our calculations reveal that compared to the QM results the MM approaches can appropriately reproduce the strength of π-π interactions for both configurations, and more importantly, the energy difference between them, indicating that the various contributions to π-π interactions have been implicitly included in the van der Waals parameters of the standard MM force fields. Meanwhile, these MM models are less accurate in predicting the exact structural binding patterns (matching surface), meaning there are still rooms to be improved. In addition, we have provided a comprehensive and reliable QM picture for the π-π interactions of aromatic molecules with CNTs in gas phase, which might be used as a benchmark for future force field developments.

Amino acid analogues bind to carbon nanotube via π-π interactions: comparison of molecular mechanical and quantum mechanical calculations.

PubMed

Yang, Zaixing; Wang, Zhigang; Tian, Xingling; Xiu, Peng; Zhou, Ruhong

2012-01-14

Understanding the interaction between carbon nanotubes (CNTs) and biomolecules is essential to the CNT-based nanotechnology and biotechnology. Some recent experiments have suggested that the π-π stacking interactions between protein's aromatic residues and CNTs might play a key role in their binding, which raises interest in large scale modeling of protein-CNT complexes and associated π-π interactions at atomic detail. However, there is concern on the accuracy of classical fixed-charge molecular force fields due to their classical treatments and lack of polarizability. Here, we study the binding of three aromatic residue analogues (mimicking phenylalanine, tyrosine, and tryptophan) and benzene to a single-walled CNT, and compare the molecular mechanical (MM) calculations using three popular fixed-charge force fields (OPLSAA, AMBER, and CHARMM), with quantum mechanical (QM) calculations using the density-functional tight-binding method with the inclusion of dispersion correction (DFTB-D). Two typical configurations commonly found in π-π interactions are used, one with the aromatic rings parallel to the CNT surface (flat), and the other perpendicular (edge). Our calculations reveal that compared to the QM results the MM approaches can appropriately reproduce the strength of π-π interactions for both configurations, and more importantly, the energy difference between them, indicating that the various contributions to π-π interactions have been implicitly included in the van der Waals parameters of the standard MM force fields. Meanwhile, these MM models are less accurate in predicting the exact structural binding patterns (matching surface), meaning there are still rooms to be improved. In addition, we have provided a comprehensive and reliable QM picture for the π-π interactions of aromatic molecules with CNTs in gas phase, which might be used as a benchmark for future force field developments.

Improving the Force Field Description of Tyrosine-Choline Cation-π Interactions: QM Investigation of Phenol-N(Me)4+ Interactions.

PubMed

Khan, Hanif M; Grauffel, Cédric; Broer, Ria; MacKerell, Alexander D; Havenith, Remco W A; Reuter, Nathalie

2016-11-08

Cation-π interactions between tyrosine amino acids and compounds containing N,N,N-trimethylethanolammonium (N(CH 3 ) 3 ) are involved in the recognition of histone tails by chromodomains and in the recognition of phosphatidylcholine (PC) phospholipids by membrane-binding proteins. Yet, the lack of explicit polarization or charge transfer effects in molecular mechanics force fields raises questions about the reliability of the representation of these interactions in biomolecular simulations. Here, we investigate the nature of phenol-tetramethylammonium (TMA) interactions using quantum mechanical (QM) calculations, which we also use to evaluate the accuracy of the additive CHARMM36 and Drude polarizable force fields in modeling tyrosine-choline interactions. We show that the potential energy surface (PES) obtained using SAPT2+/aug-cc-pVDZ compares well with the large basis-set CCSD(T) PES when TMA approaches the phenol ring perpendicularly. Furthermore, the SAPT energy decomposition reveals comparable contributions from electrostatics and dispersion in phenol-TMA interactions. We then compared the SAPT2+/aug-cc-pVDZ PES obtained along various approach directions to the corresponding PES obtained with CHARMM, and we show that the force field accurately reproduces the minimum distances while the interaction energies are underestimated. The use of the Drude polarizable force field significantly improves the interaction energies but decreases the agreement on distances at energy minima. The best agreement between force field and QM PES is obtained by modifying the Lennard-Jones terms for atom pairs involved in the phenol-TMA cation-π interactions. This is further shown to improve the correlation between the occupancy of tyrosine-choline cation-π interactions obtained from molecular dynamics simulations of a bilayer-bound bacterial phospholipase and experimental affinity data of the wild-type protein and selected mutants.

3D-QSAR based on quantum-chemical molecular fields: toward an improved description of halogen interactions.

PubMed

Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Müller, Marco; Schmidt, Friedemann; Clark, Timothy

2012-09-24

Current 3D-QSAR methods such as CoMFA or CoMSIA make use of classical force-field approaches for calculating molecular fields. Thus, they can not adequately account for noncovalent interactions involving halogen atoms like halogen bonds or halogen-π interactions. These deficiencies in the underlying force fields result from the lack of treatment of the anisotropy of the electron density distribution of those atoms, known as the "σ-hole", although recent developments have begun to take specific interactions such as halogen bonding into account. We have now replaced classical force field derived molecular fields by local properties such as the local ionization energy, local electron affinity, or local polarizability, calculated using quantum-mechanical (QM) techniques that do not suffer from the above limitation for 3D-QSAR. We first investigate the characteristics of QM-based local property fields to show that they are suitable for statistical analyses after suitable pretreatment. We then analyze these property fields with partial least-squares (PLS) regression to predict biological affinities of two data sets comprising factor Xa and GABA-A/benzodiazepine receptor ligands. While the resulting models perform equally well or even slightly better in terms of consistency and predictivity than the classical CoMFA fields, the most important aspect of these augmented field-types is that the chemical interpretation of resulting QM-based property field models reveals unique SAR trends driven by electrostatic and polarizability effects, which cannot be extracted directly from CoMFA electrostatic maps. Within the factor Xa set, the interaction of chlorine and bromine atoms with a tyrosine side chain in the protease S1 pocket are correctly predicted. Within the GABA-A/benzodiazepine ligand data set, PLS models of high predictivity resulted for our QM-based property fields, providing novel insights into key features of the SAR for two receptor subtypes and cross-receptor selectivity of the ligands. The detailed interpretation of regression models derived using improved QM-derived property fields thus provides a significant advantage by revealing chemically meaningful correlations with biological activity and helps in understanding novel structure-activity relationship features. This will allow such knowledge to be used to design novel molecules on the basis of interactions additional to steric and hydrogen-bonding features.

Introducing time-dependent molecular fields: a new derivation of the wave equations

NASA Astrophysics Data System (ADS)

Baer, Michael

2018-02-01

This article is part of a series of articles trying to establish the concept molecular field. The theory that induced us to introduce this novel concept is based on the Born-Huang expansion as applied to the Schroedinger equation that describes the interaction of a molecular system with an external electric field. Assuming the molecular system is made up of two coupled adiabatic states the theory leads from a single spatial curl equation, two space-time curl equations and one single space-time divergent equation to a pair of decoupled wave equations usually encountered within the theory of fields. In the present study, just like in the previous study [see Baer et al., Mol. Phys. 114, 227 (2016)] the wave equations are derived for an electric field having two features: (a) its intensity is high enough; (b) its duration is short enough. Although not all the findings are new the derivation, in the present case, is new, straightforward, fluent and much friendlier as compared to the previous one and therefore should be presented again. For this situation the study reveals that the just described interaction creates two fields that coexist within a molecule: one is a novel vectorial field formed via the interaction of the electric field with the Born-Huang non-adiabatic coupling terms (NACTs) and the other is an ordinary, scalar, electric field essentially identical to the original electric field. Section 4 devoted to the visualization of the outcomes via two intersecting Jahn-Teller cones which contain NACTs that become singular at the intersection point of these cones. Finally, the fact that eventually we are facing a kind of a cosmic situation may bring us to speculate that singular NACTs are a result of cosmic phenomena. Thus, if indeed this singularity is somehow connected to reality then, like other singularities in physics, it is formed at (or immediately after) the Big Bang and consequently, guarantees the formation of molecules.

Electron correlation by polarization of interacting densities

NASA Astrophysics Data System (ADS)

Whitten, Jerry L.

2017-02-01

Coulomb interactions that occur in electronic structure calculations are correlated by allowing basis function components of the interacting densities to polarize dynamically, thereby reducing the magnitude of the interaction. Exchange integrals of molecular orbitals are not correlated. The modified Coulomb interactions are used in single-determinant or configuration interaction calculations. The objective is to account for dynamical correlation effects without explicitly introducing higher spherical harmonic functions into the molecular orbital basis. Molecular orbital densities are decomposed into a distribution of spherical components that conserve the charge and each of the interacting components is considered as a two-electron wavefunction embedded in the system acted on by an average field Hamiltonian plus r12-1. A method of avoiding redundancy is described. Applications to atoms, negative ions, and molecules representing different types of bonding and spin states are discussed.

Workshop on Molecular Evolution

NASA Technical Reports Server (NTRS)

Cummings, Michael P.

2004-01-01

Molecular evolution has become the nexus of many areas of biological research. It both brings together and enriches such areas as biochemistry, molecular biology, microbiology, population genetics, systematics, developmental biology, genomics, bioinformatics, in vitro evolution, and molecular ecology. The Workshop provides an important contribution to these fields in that it promotes interdisciplinary research and interaction, and thus provides a glue that sticks together disparate fields. Due to the wide range of fields addressed by the study of molecular evolution, it is difficult to offer a comprehensive course in a university setting. It is rare for a single institution to maintain expertise in all necessary areas. In contrast, the Workshop is uniquely able to provide necessary breadth and depth by utilizing a large number of faculty with appropriate expertise. Furthermore, the flexible nature of the Workshop allows for rapid adaptation to changes in the dynamic field of molecular evolution. For example, the 2003 Workshop included recently emergent research areas of molecular evolution of development and genomics.

Adiabatic perturbation theory for atoms and molecules in the low-frequency regime

NASA Astrophysics Data System (ADS)

Martiskainen, Hanna; Moiseyev, Nimrod

2017-12-01

There is an increasing interest in the photoinduced dynamics in the low frequency, ω, regime. The multiphoton absorptions by molecules in strong laser fields depend on the polarization of the laser and on the molecular structure. The unique properties of the interaction of atoms and molecules with lasers in the low-frequency regime imply new concepts and directions in strong-field light-matter interactions. Here we represent a perturbational approach for the calculations of the quasi-energy spectrum in the low-frequency regime, which avoids the construction of the Floquet operator with extremely large number of Floquet channels. The zero-order Hamiltonian in our perturbational approach is the adiabatic Hamiltonian where the atoms/molecules are exposed to a dc electric field rather than to ac-field. This is in the spirit of the first step in the Corkum three-step model. The second-order perturbation correction terms are obtained when i ℏ ω ∂/∂ τ serves as a perturbation and τ is a dimensionless variable. The second-order adiabatic perturbation scheme is found to be an excellent approach for calculating the ac-field Floquet solutions in our test case studies of a simple one-dimensional time-periodic model Hamiltonian. It is straightforward to implement the perturbation approach presented here for calculating atomic and molecular energy shifts (positions) due to the interaction with low-frequency ac-fields using high-level electronic structure methods. This is enabled since standard quantum chemistry packages allow the calculations of atomic and molecular energy shifts due to the interaction with dc-fields. In addition to the shift of the energy positions, the energy widths (inverse lifetimes) can be obtained at the same level of theory. These energy shifts are functions of the laser parameters (low frequency, intensity, and polarization).

Molecular dynamics simulations of fluid cyclopropane with MP2/CBS-fitted intermolecular interaction potentials

NASA Astrophysics Data System (ADS)

Ho, Yen-Ching; Wang, Yi-Siang; Chao, Sheng D.

2017-08-01

Modeling fluid cycloalkanes with molecular dynamics simulations has proven to be a very challenging task partly because of lacking a reliable force field based on quantum chemistry calculations. In this paper, we construct an ab initio force field for fluid cyclopropane using the second-order Møller-Plesset perturbation theory. We consider 15 conformers of the cyclopropane dimer for the orientation sampling. Single-point energies at important geometries are calibrated by the coupled cluster with single, double, and perturbative triple excitation method. Dunning's correlation consistent basis sets (up to aug-cc-pVTZ) are used in extrapolating the interaction energies at the complete basis set limit. The force field parameters in a 9-site Lennard-Jones model are regressed by the calculated interaction energies without using empirical data. With this ab initio force field, we perform molecular dynamics simulations of fluid cyclopropane and calculate both the structural and dynamical properties. We compare the simulation results with those using an empirical force field and obtain a quantitative agreement for the detailed atom-wise radial distribution functions. The experimentally observed gross radial distribution function (extracted from the neutron scattering measurements) is well reproduced in our simulation. Moreover, the calculated self-diffusion coefficients and shear viscosities are in good agreement with the experimental data over a wide range of thermodynamic conditions. To the best of our knowledge, this is the first ab initio force field which is capable of competing with empirical force fields for simulating fluid cyclopropane.

A molecular-field approximation for quantum crystals. Ph.D. Thesis; [considering ground state properties

NASA Technical Reports Server (NTRS)

Danilowicz, R.

1973-01-01

Ground-state properties of quantum crystals have received considerable attention from both theorists and experimentalists. The theoretical results have varied widely with the Monte Carlo calculations being the most successful. The molecular field approximation yields ground-state properties which agree closely with the Monte Carlo results. This approach evaluates the dynamical behavior of each pair of molecules in the molecular field of the other N-2 molecules. In addition to predicting ground-state properties that agree well with experiment, this approach yields data on the relative importance of interactions of different nearest neighbor pairs.

Liquid-phase characterization of molecular interactions in polyunsaturated and n-fatty acid methyl esters by (1)H low-field nuclear magnetic resonance.

PubMed

Meiri, Nitzan; Berman, Paula; Colnago, Luiz Alberto; Moraes, Tiago Bueno; Linder, Charles; Wiesman, Zeev

2015-01-01

To identify and develop the best renewable and low carbon footprint biodiesel substitutes for petroleum diesel, the properties of different biodiesel candidates should be studied and characterized with respect to molecular structures versus biodiesel liquid property relationships. In our previous paper, (1)H low-field nuclear magnetic resonance (LF-NMR) relaxometry was investigated as a tool for studying the liquid-phase molecular packing interactions and morphology of fatty acid methyl esters (FAMEs). The technological potential was demonstrated with oleic acid and methyl oleate standards having similar alkyl chains but different head groups. In the present work, molecular organization versus segmental and translational movements of FAMEs in their pure liquid phase, with different alkyl chain lengths (10-20 carbons) and degrees of unsaturation (0-3 double bonds), were studied with (1)H LF-NMR relaxometry and X-ray, (1)H LF-NMR diffusiometry, and (13)C high-field NMR. Based on density values and X-ray measurements, it was proposed that FAMEs possess a liquid crystal-like order above their melting point, consisting of random liquid crystal aggregates with void spaces between them, whose morphological properties depend on chain length and degree of unsaturation. FAMEs were also found to exhibit different degrees of rotational and translational motions, which were rationalized by chain organization within the clusters, and the degree and type of molecular interactions and temperature effects. At equivalent fixed temperature differences from melting point, saturated FAME molecules were found to have similar translational motion regardless of chain length, expressed by viscosity, self-diffusion coefficients, and spin-spin (T 2) (1)H LF-NMR. T 2 distributions suggest increased alkyl chain rigidity, and reduced temperature response of the peaks' relative contribution with increasing unsaturation is a direct result of the alkyl chain's morphological packing and molecular interactions. Both the peaks' assignments for T 2 distributions of FAMEs and the model for their liquid crystal-like morphology in the liquid phase were confirmed. The study of morphological structures within liquids and their response to temperature changes by (1)H LF-NMR has a high value in the field of biodiesel and other research and applied disciplines in numerous physicochemical- and organizational-based properties, processes, and mechanisms of alkyl chains, molecular interactions, and morphologies.

Tailored Surfaces/Assemblies for Molecular Plasmonics and Plasmonic Molecular Electronics.

PubMed

Lacroix, Jean-Christophe; Martin, Pascal; Lacaze, Pierre-Camille

2017-06-12

Molecular plasmonics uses and explores molecule-plasmon interactions on metal nanostructures for spectroscopic, nanophotonic, and nanoelectronic devices. This review focuses on tailored surfaces/assemblies for molecular plasmonics and describes active molecular plasmonic devices in which functional molecules and polymers change their structural, electrical, and/or optical properties in response to external stimuli and that can dynamically tune the plasmonic properties. We also explore an emerging research field combining molecular plasmonics and molecular electronics.

Molecular dynamics study of response of liquid N,N-dimethylformamide to externally applied electric field using a polarizable force field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Weimin; Niu, Haitao; Lin, Tong

2014-01-28

The behavior of Liquid N,N-dimethylformamide subjected to a wide range of externally applied electric fields (from 0.001 V/nm to 1 V/nm) has been investigated through molecular dynamics simulation. To approach the objective the AMOEBA polarizable force field was extended to include the interaction of the external electric field with atomic partial charges and the contribution to the atomic polarization. The simulation results were evaluated with quantum mechanical calculations. The results from the present force field for the liquid at normal conditions were compared with the experimental and molecular dynamics results with non-polarizable and other polarizable force fields. The uniform externalmore » electric fields of higher than 0.01 V/nm have a significant effect on the structure of the liquid, which exhibits a variation in numerous properties, including molecular polarization, local cluster structure, rotation, alignment, energetics, and bulk thermodynamic and structural properties.« less

Fanconi Anemia Proteins and Their Interacting Partners: A Molecular Puzzle

PubMed Central

Kaddar, Tagrid; Carreau, Madeleine

2012-01-01

In recent years, Fanconi anemia (FA) has been the subject of intense investigations, primarily in the DNA repair research field. Many discoveries have led to the notion of a canonical pathway, termed the FA pathway, where all FA proteins function sequentially in different protein complexes to repair DNA cross-link damages. Although a detailed architecture of this DNA cross-link repair pathway is emerging, the question of how a defective DNA cross-link repair process translates into the disease phenotype is unresolved. Other areas of research including oxidative metabolism, cell cycle progression, apoptosis, and transcriptional regulation have been studied in the context of FA, and some of these areas were investigated before the fervent enthusiasm in the DNA repair field. These other molecular mechanisms may also play an important role in the pathogenesis of this disease. In addition, several FA-interacting proteins have been identified with roles in these “other” nonrepair molecular functions. Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle. PMID:22737580

Semiclassical theory of the self-consistent vibration-rotation fields and its application to the bending-rotation interaction in the H{sub 2}O molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skalozub, A.S.; Tsaune, A.Ya.

1994-12-01

A new approach for analyzing the highly excited vibration-rotation (VR) states of nonrigid molecules is suggested. It is based on the separation of the vibrational and rotational terms in the molecular VR Hamiltonian by introducing periodic auxiliary fields. These fields transfer different interactions within a molecule and are treated in terms of the mean-field approximation. As a result, the solution of the stationary Schroedinger equation with the VR Hamiltonian amounts to a quantization of the Berry phase in a problem of the molecular angular-momentum motion in a certain periodic VR field (rotational problem). The quantization procedure takes into account themore » motion of the collective vibrational variables in the appropriate VR potentials (vibrational problem). The quantization rules, the mean-field configurations of auxiliary interactions, and the solutions to the Schrodinger equations for the vibrational and rotational problems are self-consistently connected with one another. The potentialities of the theory are demonstrated by the bending-rotation interaction modeled by the Bunker-Landsberg potential function in the H{sub 2} molecule. The calculations are compared with both the results of the exact computations and those of other approximate methods. 32 refs., 4 tabs.« less

LigParGen web server: an automatic OPLS-AA parameter generator for organic ligands

PubMed Central

Dodda, Leela S.

2017-01-01

Abstract The accurate calculation of protein/nucleic acid–ligand interactions or condensed phase properties by force field-based methods require a precise description of the energetics of intermolecular interactions. Despite the progress made in force fields, small molecule parameterization remains an open problem due to the magnitude of the chemical space; the most critical issue is the estimation of a balanced set of atomic charges with the ability to reproduce experimental properties. The LigParGen web server provides an intuitive interface for generating OPLS-AA/1.14*CM1A(-LBCC) force field parameters for organic ligands, in the formats of commonly used molecular dynamics and Monte Carlo simulation packages. This server has high value for researchers interested in studying any phenomena based on intermolecular interactions with ligands via molecular mechanics simulations. It is free and open to all at jorgensenresearch.com/ligpargen, and has no login requirements. PMID:28444340

Prediction of molecular crystal structures by a crystallographic QM/MM model with full space-group symmetry.

PubMed

Mörschel, Philipp; Schmidt, Martin U

2015-01-01

A crystallographic quantum-mechanical/molecular-mechanical model (c-QM/MM model) with full space-group symmetry has been developed for molecular crystals. The lattice energy was calculated by quantum-mechanical methods for short-range interactions and force-field methods for long-range interactions. The quantum-mechanical calculations covered the interactions within the molecule and the interactions of a reference molecule with each of the surrounding 12-15 molecules. The interactions with all other molecules were treated by force-field methods. In each optimization step the energies in the QM and MM shells were calculated separately as single-point energies; after adding both energy contributions, the crystal structure (including the lattice parameters) was optimized accordingly. The space-group symmetry was maintained throughout. Crystal structures with more than one molecule per asymmetric unit, e.g. structures with Z' = 2, hydrates and solvates, have been optimized as well. Test calculations with different quantum-mechanical methods on nine small organic molecules revealed that the density functional theory methods with dispersion correction using the B97-D functional with 6-31G* basis set in combination with the DREIDING force field reproduced the experimental crystal structures with good accuracy. Subsequently the c-QM/MM method was applied to nine compounds from the CCDC blind tests resulting in good energy rankings and excellent geometric accuracies.

Let's get honest about sampling.

PubMed

Mobley, David L

2012-01-01

Molecular simulations see widespread and increasing use in computation and molecular design, especially within the area of molecular simulations applied to biomolecular binding and interactions, our focus here. However, force field accuracy remains a concern for many practitioners, and it is often not clear what level of accuracy is really needed for payoffs in a discovery setting. Here, I argue that despite limitations of today's force fields, current simulation tools and force fields now provide the potential for real benefits in a variety of applications. However, these same tools also provide irreproducible results which are often poorly interpreted. Continued progress in the field requires more honesty in assessment and care in evaluation of simulation results, especially with respect to convergence.

Experiments on the Dynamics of Molecular Processes: a Chronicle of Fifty Years

NASA Astrophysics Data System (ADS)

Boato, Giovanni; Volpi, Gian Gualberto

1999-10-01

This paper reviews the way in which, in the Italy of the years immediately after World War II, interest in the dynamics of molecular processes was awakened. The narrative begins with the work of a small number of chemists and physicists who, in the initial stage, interacted closely. In the course of the years, their interests diverged and younger people joined the newly formed groups. Even now, after half a century, a common approach can still to be seen regarding how to attack problems and perform experiments. Experimental work is discussed, bringing out the common viewpoint of fields as diverse as mass spectrometry, isotope effects, chemical kinetics, molecular beams, molecule-molecule interactions, molecule-ion interactions, molecule-surface interactions, and plasma chemistry.

Nature and magnitude of aromatic base stacking in DNA and RNA: Quantum chemistry, molecular mechanics, and experiment.

PubMed

Sponer, Jiří; Sponer, Judit E; Mládek, Arnošt; Jurečka, Petr; Banáš, Pavel; Otyepka, Michal

2013-12-01

Base stacking is a major interaction shaping up and stabilizing nucleic acids. During the last decades, base stacking has been extensively studied by experimental and theoretical methods. Advanced quantum-chemical calculations clarified that base stacking is a common interaction, which in the first approximation can be described as combination of the three most basic contributions to molecular interactions, namely, electrostatic interaction, London dispersion attraction and short-range repulsion. There is not any specific π-π energy term associated with the delocalized π electrons of the aromatic rings that cannot be described by the mentioned contributions. The base stacking can be rather reasonably approximated by simple molecular simulation methods based on well-calibrated common force fields although the force fields do not include nonadditivity of stacking, anisotropy of dispersion interactions, and some other effects. However, description of stacking association in condensed phase and understanding of the stacking role in biomolecules remain a difficult problem, as the net base stacking forces always act in a complex and context-specific environment. Moreover, the stacking forces are balanced with many other energy contributions. Differences in definition of stacking in experimental and theoretical studies are explained. Copyright © 2013 Wiley Periodicals, Inc.

Molecular-dynamics study on characteristics of energy and tangential momentum accommodation coefficients

NASA Astrophysics Data System (ADS)

Yamaguchi, Hiroki; Matsuda, Yu; Niimi, Tomohide

2017-07-01

Gas-surface interaction is studied by the molecular dynamics method to investigate qualitatively characteristics of accommodation coefficients. A large number of trajectories of gas molecules colliding to and scattering from a surface are statistically analyzed to calculate the energy (thermal) accommodation coefficient (EAC) and the tangential momentum accommodation coefficient (TMAC). Considering experimental measurements of the accommodation coefficients, the incident velocities are stochastically sampled to represent a bulk condition. The accommodation coefficients for noble gases show qualitative coincidence with experimental values. To investigate characteristics of these accommodation coefficients in detail, the gas-surface interaction is parametrically studied by varying the molecular mass of gas, the gas-surface interaction strength, and the molecular size of gas, one by one. EAC increases with increasing every parameter, while TMAC increases with increasing the interaction strength, but decreases with increasing the molecular mass and the molecular size. Thus, contradictory results in experimentally measured TMAC for noble gases could result from the difference between the surface conditions employed in the measurements in the balance among the effective parameters of molecular mass, interaction strength, and molecular size, due to surface roughness and/or adsorbed molecules. The accommodation coefficients for a thermo-fluid dynamics field with a temperature difference between gas and surface and a bulk flow at the same time are also investigated.

Hybrid particle-field molecular dynamics simulation for polyelectrolyte systems.

PubMed

Zhu, You-Liang; Lu, Zhong-Yuan; Milano, Giuseppe; Shi, An-Chang; Sun, Zhao-Yan

2016-04-14

To achieve simulations on large spatial and temporal scales with high molecular chemical specificity, a hybrid particle-field method was proposed recently. This method is developed by combining molecular dynamics and self-consistent field theory (MD-SCF). The MD-SCF method has been validated by successfully predicting the experimentally observable properties of several systems. Here we propose an efficient scheme for the inclusion of electrostatic interactions in the MD-SCF framework. In this scheme, charged molecules are interacting with the external fields that are self-consistently determined from the charge densities. This method is validated by comparing the structural properties of polyelectrolytes in solution obtained from the MD-SCF and particle-based simulations. Moreover, taking PMMA-b-PEO and LiCF3SO3 as examples, the enhancement of immiscibility between the ion-dissolving block and the inert block by doping lithium salts into the copolymer is examined by using the MD-SCF method. By employing GPU-acceleration, the high performance of the MD-SCF method with explicit treatment of electrostatics facilitates the simulation study of many problems involving polyelectrolytes.

Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics

PubMed Central

Barrère, Florence; van Blitterswijk, Clemens A; de Groot, Klaas

2006-01-01

Calcium phosphate bioceramics are widely used in orthopedic and dental applications and porous scaffolds made of them are serious candidates in the field of bone tissue engineering. They have superior properties for the stimulation of bone formation and bone bonding, both related to the specific interactions of their surface with the extracellular fluids and cells, ie, ionic exchanges, superficial molecular rearrangement and cellular activity. PMID:17717972

Nonlinear electromagnetic interactions in energetic materials

DOE PAGES

Wood, Mitchell Anthony; Dalvit, Diego Alejandro; Moore, David Steven

2016-01-12

We study the scattering of electromagnetic waves in anisotropic energetic materials. Nonlinear light-matter interactions in molecular crystals result in frequency-conversion and polarization changes. Applied electromagnetic fields of moderate intensity can induce these nonlinear effects without triggering chemical decomposition, offering a mechanism for the nonionizing identification of explosives. We use molecular-dynamics simulations to compute such two-dimensional THz spectra for planar slabs made of pentaerythritol tetranitrate and ammonium nitrate. Finally, we discuss third-harmonic generation and polarization-conversion processes in such materials. These observed far-field spectral features of the reflected or transmitted light may serve as an alternative tool for standoff explosive detection.

Radiative Enhancement of Linear and Third-Order Vibrational Excitations by an Array of Infrared Plasmonic Antennas.

PubMed

Gandman, Andrey; Mackin, Robert T; Cohn, Bar; Rubtsov, Igor V; Chuntonov, Lev

2018-05-22

Infrared gold antennas localize enhanced near fields close to the metal surface, when excited at the frequency of their plasmon resonance, and amplify vibrational signals from the nearby molecules. We study the dependence of the signal enhancement on the thickness of a polymer film containing vibrational chromophores, deposited on the antenna array, using linear (FTIR) and third-order femtosecond vibrational spectroscopy (transient absorption and 2DIR). Our results show that for a film thickness beyond only a few nanometers the near-field interaction is not sufficient to account for the magnitude of the observed signal, which nevertheless has a clear Fano line shape, suggesting a radiative origin of the molecule-plasmon interaction. The mutual radiative damping of plasmonic and molecular transitions leads to the spectroscopic signal of a molecular vibrational excitation to be enhanced by up to a factor of 50 in the case of linear spectroscopy and over 2000 in the case of third-order spectroscopy. A qualitative explanation for the observed effect is given by the extended coupled oscillators model, which takes into account both near-field and radiative interactions between the plasmonic and molecular transitions.

Perspectives on the simulation of protein–surface interactions using empirical force field methods

PubMed Central

Latour, Robert A.

2014-01-01

Protein–surface interactions are of fundamental importance for a broad range of applications in the fields of biomaterials and biotechnology. Present experimental methods are limited in their ability to provide a comprehensive depiction of these interactions at the atomistic level. In contrast, empirical force field based simulation methods inherently provide the ability to predict and visualize protein–surface interactions with full atomistic detail. These methods, however, must be carefully developed, validated, and properly applied before confidence can be placed in results from the simulations. In this perspectives paper, I provide an overview of the critical aspects that I consider being of greatest importance for the development of these methods, with a focus on the research that my combined experimental and molecular simulation groups have conducted over the past decade to address these issues. These critical issues include the tuning of interfacial force field parameters to accurately represent the thermodynamics of interfacial behavior, adequate sampling of these types of complex molecular systems to generate results that can be comparable with experimental data, and the generation of experimental data that can be used for simulation results evaluation and validation. PMID:25028242

Simplified TiO2 force fields for studies of its interaction with biomolecules

NASA Astrophysics Data System (ADS)

Luan, Binquan; Huynh, Tien; Zhou, Ruhong

2015-06-01

Engineered TiO2 nanoparticles have been routinely applied in nanotechnology, as well as in cosmetics and food industries. Despite active experimental studies intended to clarify TiO2's biological effects, including potential toxicity, the relation between experimentally inferred nanotoxicity and industry standards for safely applying nanoparticles remains somewhat ambiguous with justified concerns. Supplemental to experiments, molecular dynamics simulations have proven to be efficacious in investigating the molecular mechanism of a biological process occurring at nanoscale. In this article, to facilitate the nanotoxicity and nanomedicine research related to this important metal oxide, we provide a simplified force field, based on the original Matsui-Akaogi force field but compatible to the Lennard-Jones potentials normally used in modeling biomolecules, for simulating TiO2 nanoparticles interacting with biomolecules. The force field parameters were tested in simulating the bulk structure of TiO2, TiO2 nanoparticle-water interaction, as well as the adsorption of proteins on the TiO2 nanoparticle. We demonstrate that these simulation results are consistent with experimental data/observations. We expect that simulations will help to better understand the interaction between TiO2 and molecules.

Molecular toxicity of nanomaterials.

PubMed

Chang, Xue-Ling; Yang, Sheng-Tao; Xing, Gengmei

2014-10-01

With the rapid developments in the fields of nanoscience and nanotechnlogy, more and more nanomaterials and their based consumer products have been used into our daily life. The safety concerns of nanomaterials have been well recognized by the scientific community and the public. Molecular mechanism of interactions between nanomaterials and biosystems is the most essential topic and final core of the biosafety. In the last two decades, nanotoxicology developed very fast and toxicity phenomena of nanomaterials have been reported. To achieve better understanding and detoxication of nanomaterials, thorough studies of nanotoxicity at molecular level are important. The interactions between nanomaterials and biomolecules have been widely investigated as the first step toward the molecular nanotoxicology. The consequences of such interactions have been discussed in the literature. Besides this, the chemical mechanism of nanotoxicology is gaining more attention, which would lead to a better design of nontoxic nanomaterials. In this review, we focus on the molecular nanotoxicology and explore the toxicity of nanomaterials at molecular level. The molecular level studies of nanotoxicology are summarized and the published nanotoxicological data are revisited.

Molecular dynamics simulations of highly crowded amino acid solutions: comparisons of eight different force field combinations with experiment and with each other

PubMed Central

Andrews, Casey T.

2013-01-01

Although it is now commonly accepted that the highly crowded conditions encountered inside biological cells have the potential to significantly alter the thermodynamic properties of biomolecules, it is not known to what extent the thermodynamics of fundamental types of interactions such as salt bridges and hydrophobic interactions are strengthened or weakened by high biomolecular concentrations. As one way of addressing this question we have performed a series of all-atom explicit solvent molecular dynamics (MD) simulations to investigate the effect of increasing solute concentration on the behavior of four types of zwitterionic amino acids in aqueous solution. We have simulated systems containing glycine, valine, phenylalanine or asparagine at concentrations of 50, 100, 200 and 300 mg/ml. Each molecular system has been simulated for 1 μs in order to obtain statistically converged estimates of thermodynamic parameters, and each has been conducted with 8 different force fields and water models; the combined simulation time is 128 μs. The density, viscosity, and dielectric increments of the four amino acids calculated from the simulations have been compared to corresponding experimental measurements. While all of the force fields perform well at reproducing the density increments, discrepancies for the viscosity and dielectric increments raise questions both about the accuracy of the simulation force fields and, in certain cases, the experimental data. We also observe large differences between the various force fields' descriptions of the interaction thermodynamics of salt bridges and, surprisingly, these differences also lead to qualitatively different predictions of their dependences on solute concentration. For the aliphatic interactions of valine sidechains, fewer differences are observed between the force fields, but significant differences are again observed for aromatic interactions of phenylalanine sidechains. Taken together, the results highlight the potential power of using explicit-solvent simulation methods to understand behavior in concentrated systems but also hint at potential difficulties in using these methods to obtain consistent views of behavior in intracellular environments. PMID:24409104

Activateable Imaging Probes Light Up Inside Cancer Cells | Center for Cancer Research

Cancer.gov

Imaging can be used to help diagnose cancer as well as monitor tumor progression and response to treatment. The field of molecular imaging focuses on techniques capable of detecting specific molecular targets associated with cancer; the agents used for molecular imaging—often called probes—are multifunctional, with components that allow them to both interact with their molecular target and emit a detectable signal.

Quantum Sensors for the Generating Functional of Interacting Quantum Field Theories

NASA Astrophysics Data System (ADS)

Bermudez, A.; Aarts, G.; Müller, M.

2017-10-01

Difficult problems described in terms of interacting quantum fields evolving in real time or out of equilibrium abound in condensed-matter and high-energy physics. Addressing such problems via controlled experiments in atomic, molecular, and optical physics would be a breakthrough in the field of quantum simulations. In this work, we present a quantum-sensing protocol to measure the generating functional of an interacting quantum field theory and, with it, all the relevant information about its in- or out-of-equilibrium phenomena. Our protocol can be understood as a collective interferometric scheme based on a generalization of the notion of Schwinger sources in quantum field theories, which make it possible to probe the generating functional. We show that our scheme can be realized in crystals of trapped ions acting as analog quantum simulators of self-interacting scalar quantum field theories.

Beyond Born-Mayer: Improved models for short-range repulsion in ab initio force fields

DOE PAGES

Van Vleet, Mary J.; Misquitta, Alston J.; Stone, Anthony J.; ...

2016-06-23

Short-range repulsion within inter-molecular force fields is conventionally described by either Lennard-Jones or Born-Mayer forms. Despite their widespread use, these simple functional forms are often unable to describe the interaction energy accurately over a broad range of inter-molecular distances, thus creating challenges in the development of ab initio force fields and potentially leading to decreased accuracy and transferability. Herein, we derive a novel short-range functional form based on a simple Slater-like model of overlapping atomic densities and an iterated stockholder atom (ISA) partitioning of the molecular electron density. We demonstrate that this Slater-ISA methodology yields a more accurate, transferable, andmore » robust description of the short-range interactions at minimal additional computational cost compared to standard Lennard-Jones or Born-Mayer approaches. Lastly, we show how this methodology can be adapted to yield the standard Born-Mayer functional form while still retaining many of the advantages of the Slater-ISA approach.« less

Charge transport in organic multi-layer devices under electric and optical fields

NASA Astrophysics Data System (ADS)

Park, June Hyoung

2007-12-01

Charge transport in small organic molecules and conjugated conducting polymers under electric or optical fields is studied by using field effect transistors and photo-voltaic cells with multiple thin layers. With these devices, current under electric field, photo-current under optical field, and luminescence of optical materials are measured to characterize organic and polymeric materials. For electric transport studies, poly(3,4-ethylenedioxythiophene) doped by polystyrenesulfonic acid is used, which is conductive with conductivity of approximately 25 S/cm. Despite their high conductance, field effect transistors based on the films are successfully built and characterized by monitoring modulations of drain current by gate voltage and IV characteristic curves. Due to very thin insulating layers of poly(vinylphenol), the transistors are relative fast under small gate voltage variation although heavy ions are involved in charge transport. In IV characteristic curves, saturation effects can be observed. Analysis using conventional field effect transistor model indicates high mobility of charge carriers, 10 cm2/V·sec, which is not consistent with the mobility of the conducting polymer. It is proposed that the effect of a small density of ions injected via polymer dielectric upon application of gate voltage and the ion compensation of key hopping sites accounts for the operation of the field effect transistors. For the studies of transport under optical field, photovoltaic cells with 3 different dendrons, which are efficient to harvest photo-excited electrons, are used. These dendrons consist of two electron-donors (tetraphenylporphyrin) and one electron-accepter (naphthalenediimide). Steady-state fluorescence measurements show that inter-molecular interaction is dominant in solid dendron film, although intra-molecular interaction is still present. Intra-molecular interaction is suggested by different fluorescence lifetimes between solutions of donor and dendrons. This intra-molecular interaction has two processes, transport via pi-stackings and transport via linking functional groups in the dendrons. IV characteristic spectra of the photovoltaic cells suggest that the transport route of photo-excited charges depends on wavelength of incident light on the cells. For excitation by the Soret band and the lowest Q band, a photo-excited electron can transport directly to a neighbor dendron. For excitation by high-energy Q bands, a photo-excited electron transports via the electron-accepters.

Molecular dynamics simulations of field emission from a prolate spheroidal tip

NASA Astrophysics Data System (ADS)

Torfason, Kristinn; Valfells, Agust; Manolescu, Andrei

2016-12-01

High resolution molecular dynamics simulations with full Coulomb interactions of electrons are used to investigate field emission from a prolate spheroidal tip. The space charge limited current is several times lower than the current calculated with the Fowler-Nordheim formula. The image-charge is taken into account with a spherical approximation, which is good around the top of the tip, i.e., region where the current is generated.

Role of magnetic and diamagnetic interactions in molecular optics and scattering

NASA Astrophysics Data System (ADS)

Forbes, Kayn A.

2018-05-01

This paper aims to explicitly clarify the role and interpretation of diamagnetic interactions between molecules and light in quantum electrodynamics. In contrast to their electric and magnetic counterparts, the diamagnetic couplings between light and matter have received relatively little interest in the field of molecular optics. This intriguing disregard of an interaction term is puzzling. The diamagnetic couplings possess unique physical properties that warrant their inclusion in any multiphoton process, and the lack of gauge invariance for paramagnetic and diamagnetic susceptibilities necessitates their inclusion. Their role and importance within nonrelativistic molecular quantum electrodynamics in the Coulomb gauge is illuminated, and it is highlighted how for any multiphoton process their inclusion should be implicit. As an indicative example of the theory presented, the diamagnetic contributions to both forward and nonforward Rayleigh scattering are derived and put into context alongside the electric and magnetic molecular responses. The work represents clarification of diamagnetic couplings in molecular quantum electrodynamics, which subsequently should proffer the study of diamagnetic interactions in molecular optics due to their unique physical attributes and necessary inclusion in multiphoton processes.

Theoretical studies of the mechanism of the action of the neurohypophyseal hormones. I. Molecular electrostatic potential (MEP) and molecular electrostatic field (MEF) maps of some vasopressin analogues

NASA Astrophysics Data System (ADS)

Liwo, Adam; Tempczyk, Anna; Grzonka, Zbigniew

1989-09-01

Continuing our theoretical studies of the oxytocin and vasopressin analogues, we have analysed the molecular electrostatic potential (MEP) and the norm of the molecular electrostatic field (MEF) of [1- β-mercaptopropionic acid]-arginine-vasopressin ([Mpa1]-AVP), [1-( β-mercapto- β,β-cyclopentamethylene)propionic acid]-arginine-vasopressin ([Cpp']-AVP), and [1-thiosalicylic acid]-arginine-vasopressin ([Ths']-AVP) whose low-energy conformations were calculated in our previous work. These compounds are known from experiment to exhibit different biological activity. The scalar fields mentioned determine the energy of interaction with either charged (MEP) or polar (MEF) species, the energy being in the second case either optimal or Boltzmann-averaged over all the possible orientations of the dipole moment versus the electrostatic field. The electrostatic interactions slowly vanish with distance and can therefore be considered to be the factor determining the molecular shape at greater distances, which can help in both predicting the interactions with the receptor at the stage of remote recognition and in finding the preferred directions of solvation by a polar solvent. In the analysis of the fields three techniques have been used: (i) the construction of maps in certain planes; (ii) the construction of maps on spheres centered in the charge center of the molecule under study and of poles chosen according to the main axes of the quadrupole moment; and (iii) the construction of surfaces corresponding to a given value of potential. The results obtained show that the shapes of both MEP and MEF are similar in the case of [Mpa1]-AVP and [Cpp1-AVP (biologically active), while some differences emerge when comparing these compounds with [Ths1]-AVP (inactive). It has also been found that both MEP and MEF depend even more strongly on conformation.

Molecular Self-Assembly Driven by London Dispersion Forces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Guo; Cooper, Valentino R; Cho, Jun-Hyung

2011-01-01

The nature and strength of intermolecular interactions are crucial to a variety of kinetic and dynamic processes at surfaces. Whereas strong chemisorption bonds are known to facilitate molecular binding, the importance of the weaker yet ubiquitous van der Waals (vdW) interactions remains elusive in most cases. Here we use first-principles calculations combined with kinetic Monte Carlo simulations to unambiguously demonstrate the vital role that vdW interactions play in molecular self-assembly, using styrene nanowire growth on silicon as a prototypical example. We find that, only when the London dispersion forces are included, accounting for the attractive parts of vdW interactions, canmore » the effective intermolecular interaction be reversed from being repulsive to attractive. Such attractive interactions, in turn, ensure the preferred growth of long wires under physically realistic conditions as observed experimentally. We further propose a cooperative scheme, invoking the application of an electric field and the selective creation of Si dangling bonds, to drastically improve the ordered arrangement of the molecular structures. The present study represents a significant step forward in the fundamental understanding and precise control of molecular self-assembly guided by London dispersion forces.« less

Empirical potential for molecular simulation of graphene nanoplatelets

NASA Astrophysics Data System (ADS)

Bourque, Alexander J.; Rutledge, Gregory C.

2018-04-01

A new empirical potential for layered graphitic materials is reported. Interatomic interactions within a single graphene sheet are modeled using a Stillinger-Weber potential. Interatomic interactions between atoms in different sheets of graphene in the nanoplatelet are modeled using a Lennard-Jones interaction potential. The potential is validated by comparing molecular dynamics simulations of tensile deformation with the reported elastic constants for graphite. The graphite is found to fracture into graphene nanoplatelets when subjected to ˜15% tensile strain normal to the basal surface of the graphene stack, with an ultimate stress of 2.0 GPa and toughness of 0.33 GPa. This force field is useful to model molecular interactions in an important class of composite systems comprising 2D materials like graphene and multi-layer graphene nanoplatelets.

Microscopic origin of electric-field-induced modulation of Curie temperature in cobalt

NASA Astrophysics Data System (ADS)

Ando, Fuyuki; Yamada, Kihiro T.; Koyama, Tomohiro; Ishibashi, Mio; Shiota, Yoichi; Moriyama, Takahiro; Chiba, Daichi; Ono, Teruo

2018-07-01

The Curie temperature T C is one of the most fundamental physical properties of ferromagnetic materials and can be described by the Weiss molecular field theory with the exchange interaction of neighboring atoms. Here, we demonstrate the electrical control of exchange coupling in cobalt films through direct magnetization measurements. We find that the reduction in magnetization with temperature, which is caused by thermal spin wave excitation and scales with Bloch’s law, clearly depends on the applied electric field. Furthermore, we confirm that the correlation between the electric-field-induced modulation of T C and that of exchange coupling follows the Weiss molecular field theory.

D2+ Molecular complex in non-uniform height quantum ribbon under crossed electric and magnetic fields

NASA Astrophysics Data System (ADS)

Suaza, Y. A.; Laroze, D.; Fulla, M. R.; Marín, J. H.

2018-05-01

The D2+ molecular complex fundamental properties in a uniform and multi-hilled semiconductor quantum ribbon under orthogonal electric and magnetic fields are theoretically studied. The energy structure is calculated by using adiabatic approximation combined with diagonalization procedure. The D2+ energy structure is more strongly controlled by the geometrical structural hills than the Coulomb interaction. The formation of vibrational and rotational states is discussed. Aharanov-Bohm oscillation patterns linked to rotational states as well as the D2+ molecular complex stability are highly sensitive to the number of hills while electric field breaks the electron rotational symmetry and removes the energy degeneration between low-lying states.

Controlling nonlinear optical response in an open four-level molecular system using quantum control of spin-orbit interaction

NASA Astrophysics Data System (ADS)

Jamshidi-Ghaleh, Kazem; Ebrahimi-hamed, Zahra; Sahrai, Mostafa

2017-10-01

This paper investigates the behavior of linear and nonlinear optical susceptibility of an open four-level molecular system, under two-step excitation based on electromagnetically induced transparency (EIT). The system was irradiated with a weak probe field and strong coupling field. It is shown that the use of a strong coupling field in the triplet states of an alkali-metal dimer can change the spin-orbit interaction (SOI). The optical response of the system can then be modified in a controllable way. The electromagnetically induced transparency transforms into electromagnetically induced absorption (EIA) in the presence of a coupling field. Changing the sign of the dispersion, this region is associated with switching subluminal and superluminal propagation. Furthermore, for the proper value of the coupling field, the controllable parameters, enhanced Kerr nonlinearity with reduced linear absorption, can be obtained under a weak probe field. With this approach, SOI can be controlled by changing only one of the controllable parameters, using triplet-triplet strong coupling with different spin state. Therefore, the desired region of the spectra can be obtained, in contrast to the other four-level system, in which at least two strong fields are used to change optical properties. This mechanism can be suitable in molecular systems or semiconductors to be used in optical bistability and fast all-optical switching devices.

Single functional group interactions with individual carbon nanotubes

NASA Astrophysics Data System (ADS)

Friddle, Raymond W.; Lemieux, Melburne C.; Cicero, Giancarlo; Artyukhin, Alexander B.; Tsukruk, Vladimir V.; Grossman, Jeffrey C.; Galli, Giulia; Noy, Aleksandr

2007-11-01

Carbon nanotubes display a consummate blend of materials properties that affect applications ranging from nanoelectronic circuits and biosensors to field emitters and membranes. These applications use the non-covalent interactions between the nanotubes and chemical functionalities, often involving a few molecules at a time. Despite their wide use, we still lack a fundamental understanding and molecular-level control of these interactions. We have used chemical force microscopy to measure the strength of the interactions of single chemical functional groups with the sidewalls of vapour-grown individual single-walled carbon nanotubes. Surprisingly, the interaction strength does not follow conventional trends of increasing polarity or hydrophobicity, and instead reflects the complex electronic interactions between the nanotube and the functional group. Ab initio calculations confirm the observed trends and predict binding force distributions for a single molecular contact that match the experimental results. Our analysis also reveals the important role of molecular linkage dynamics in determining interaction strength at the single functional group level.

Water's Interfacial Hydrogen Bonding Structure Reveals the Effective Strength of Surface-Water Interactions.

PubMed

Shin, Sucheol; Willard, Adam P

2018-06-05

We combine all-atom molecular dynamics simulations with a mean field model of interfacial hydrogen bonding to analyze the effect of surface-water interactions on the structural and energetic properties of the liquid water interface. We show that the molecular structure of water at a weakly interacting ( i.e., hydrophobic) surface is resistant to change unless the strength of surface-water interactions are above a certain threshold. We find that below this threshold water's interfacial structure is homogeneous and insensitive to the details of the disordered surface, however, above this threshold water's interfacial structure is heterogeneous. Despite this heterogeneity, we demonstrate that the equilibrium distribution of molecular orientations can be used to quantify the energetic component of the surface-water interactions that contribute specifically to modifying the interfacial hydrogen bonding network. We identify this specific energetic component as a new measure of hydrophilicity, which we refer to as the intrinsic hydropathy.

Activateable Imaging Probes Light Up Inside Cancer Cells | Center for Cancer Research

Cancer.gov

Imaging can be used to help diagnose cancer as well as monitor tumor progression and response to treatment. The field of molecular imaging focuses on techniques capable of detecting specific molecular targets associated with cancer; the agents used for molecular imaging—often called probes—are multifunctional, with components that allow them to both interact with their

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Vleet, Mary J.; Misquitta, Alston J.; Stone, Anthony J.

Short-range repulsion within inter-molecular force fields is conventionally described by either Lennard-Jones or Born-Mayer forms. Despite their widespread use, these simple functional forms are often unable to describe the interaction energy accurately over a broad range of inter-molecular distances, thus creating challenges in the development of ab initio force fields and potentially leading to decreased accuracy and transferability. Herein, we derive a novel short-range functional form based on a simple Slater-like model of overlapping atomic densities and an iterated stockholder atom (ISA) partitioning of the molecular electron density. We demonstrate that this Slater-ISA methodology yields a more accurate, transferable, andmore » robust description of the short-range interactions at minimal additional computational cost compared to standard Lennard-Jones or Born-Mayer approaches. Lastly, we show how this methodology can be adapted to yield the standard Born-Mayer functional form while still retaining many of the advantages of the Slater-ISA approach.« less

Dendrimer Interactions with Lipid Bilayer: Comparison of Force Field and Effect of Implicit vs Explicit Solvation.

PubMed

Kanchi, Subbarao; Gosika, Mounika; Ayappa, K G; Maiti, Prabal K

2018-06-13

The understanding of dendrimer interactions with cell membranes has great importance in drug/gene delivery based therapeutics. Although molecular simulations have been used to understand the nature of dendrimer interactions with lipid membranes, its dependency on available force field parameters is poorly understood. In this study, we have carried out fully atomistic molecular dynamics (MD) simulations of a protonated G3 poly(amido amine) (PAMAM) dendrimer-dimyristoylphosphatidylcholine (DMPC) lipid bilayer complex using three different force fields (FFs) namely, CHARMM, GAFF, and GROMOS in the presence of explicit water to understand the structure of the lipid-dendrimer complex and nature of their interaction. CHARMM and GAFF dendrimers initially in contact with the lipid head groups were found to move away from the lipid bilayer during the course of simulation; however, the dendrimer remained strongly bound to the lipid head groups with the GROMOS FF. Potential of the mean force (PMF) computations of the dendrimer along the bilayer normal showed a repulsive barrier (∼20 kcal/mol) between dendrimer and lipid bilayer in the case of CHARMM and GAFF force fields. In contrast, an attractive interaction (∼40 kcal/mol) is obtained with the GROMOS force field, consistent with experimental observations of membrane binding observed with lower generation G3 PAMAM dendrimers. This difference with the GROMOS dendrimer is attributed to the strong dendrimer-lipid interaction and lowered surface hydration of the dendrimer. Assessing the role of solvent, we find that the CHARMM and GAFF dendrimers strongly bind to the lipid bilayer with an implicit solvent (Generalized Born) model, whereas binding is not observed with explicit water (TIP3P). The opposing nature of dendrimer-membrane interactions in the presence of explicit and implicit solvents demonstrates that hydration effects play an important role in modulating the dendrimer-lipid interaction warranting a case for refinement of the existing dendrimer/lipid force fields.

Theory of diatomic molecules in an external electromagnetic field from first quantum mechanical principles.

PubMed

Sindelka, Milan; Moiseyev, Nimrod

2006-04-27

We study a general problem of the translational/rotational/vibrational/electronic dynamics of a diatomic molecule exposed to an interaction with an arbitrary external electromagnetic field. The theory developed in this paper is relevant to a variety of specific applications, such as alignment or orientation of molecules by lasers, trapping of ultracold molecules in optical traps, molecular optics and interferometry, rovibrational spectroscopy of molecules in the presence of intense laser light, or generation of high order harmonics from molecules. Starting from the first quantum mechanical principles, we derive an appropriate molecular Hamiltonian suitable for description of the center of mass, rotational, vibrational, and electronic molecular motions driven by the field within the electric dipole approximation. Consequently, the concept of the Born-Oppenheimer separation between the electronic and the nuclear degrees of freedom in the presence of an electromagnetic field is introduced. Special cases of the dc/ac-field limits are then discussed separately. Finally, we consider a perturbative regime of a weak dc/ac field, and obtain simple analytic formulas for the associated Born-Oppenheimer translational/rotational/vibrational molecular Hamiltonian.

Molecular near-field antenna effect in resonance hyper-Raman scattering: Intermolecular vibronic intensity borrowing of solvent from solute through dipole-dipole and dipole-quadrupole interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimada, Rintaro; Hamaguchi, Hiro-o, E-mail: hhama@nctu.edu.tw

2014-05-28

We quantitatively interpret the recently discovered intriguing phenomenon related to resonance Hyper-Raman (HR) scattering. In resonance HR spectra of all-trans-β-carotene (β-carotene) in solution, vibrations of proximate solvent molecules are observed concomitantly with the solute β-carotene HR bands. It has been shown that these solvent bands are subject to marked intensity enhancements by more than 5 orders of magnitude under the presence of β-carotene. We have called this phenomenon the molecular-near field effect. Resonance HR spectra of β-carotene in benzene, deuterated benzene, cyclohexane, and deuterated cyclohexane have been measured precisely for a quantitative analysis of this effect. The assignments of themore » observed peaks are made by referring to the infrared, Raman, and HR spectra of neat solvents. It has been revealed that infrared active and some Raman active vibrations are active in the HR molecular near-field effect. The observed spectra in the form of difference spectra (between benzene/deuterated benzene and cyclohexane/deuterated cyclohexane) are quantitatively analyzed on the basis of the extended vibronic theory of resonance HR scattering. The theory incorporates the coupling of excited electronic states of β-carotene with the vibrations of a proximate solvent molecule through solute–solvent dipole–dipole and dipole–quadrupole interactions. It is shown that the infrared active modes arise from the dipole–dipole interaction, whereas Raman active modes from the dipole–quadrupole interaction. It is also shown that vibrations that give strongly polarized Raman bands are weak in the HR molecular near-field effect. The observed solvent HR spectra are simulated with the help of quantum chemical calculations for various orientations and distances of a solvent molecule with respect to the solute. The observed spectra are best simulated with random orientations of the solvent molecule at an intermolecular distance of 10 Å.« less

Assessment of Simple Models for Molecular Simulation of Ethylene Carbonate and Propylene Carbonate as Solvents for Electrolyte Solutions.

PubMed

Chaudhari, Mangesh I; Muralidharan, Ajay; Pratt, Lawrence R; Rempe, Susan B

2018-02-12

Progress in understanding liquid ethylene carbonate (EC) and propylene carbonate (PC) on the basis of molecular simulation, emphasizing simple models of interatomic forces, is reviewed. Results on the bulk liquids are examined from the perspective of anticipated applications to materials for electrical energy storage devices. Preliminary results on electrochemical double-layer capacitors based on carbon nanotube forests and on model solid-electrolyte interphase (SEI) layers of lithium ion batteries are considered as examples. The basic results discussed suggest that an empirically parameterized, non-polarizable force field can reproduce experimental structural, thermodynamic, and dielectric properties of EC and PC liquids with acceptable accuracy. More sophisticated force fields might include molecular polarizability and Buckingham-model description of inter-atomic overlap repulsions as extensions to Lennard-Jones models of van der Waals interactions. Simple approaches should be similarly successful also for applications to organic molecular ions in EC/PC solutions, but the important case of Li[Formula: see text] deserves special attention because of the particularly strong interactions of that small ion with neighboring solvent molecules. To treat the Li[Formula: see text] ions in liquid EC/PC solutions, we identify interaction models defined by empirically scaled partial charges for ion-solvent interactions. The empirical adjustments use more basic inputs, electronic structure calculations and ab initio molecular dynamics simulations, and also experimental results on Li[Formula: see text] thermodynamics and transport in EC/PC solutions. Application of such models to the mechanism of Li[Formula: see text] transport in glassy SEI models emphasizes the advantage of long time-scale molecular dynamics studies of these non-equilibrium materials.

Correlating Nitrile IR Frequencies to Local Electrostatics Quantifies Noncovalent Interactions of Peptides and Proteins.

PubMed

Deb, Pranab; Haldar, Tapas; Kashid, Somnath M; Banerjee, Subhrashis; Chakrabarty, Suman; Bagchi, Sayan

2016-05-05

Noncovalent interactions, in particular the hydrogen bonds and nonspecific long-range electrostatic interactions are fundamental to biomolecular functions. A molecular understanding of the local electrostatic environment, consistently for both specific (hydrogen-bonding) and nonspecific electrostatic (local polarity) interactions, is essential for a detailed understanding of these processes. Vibrational Stark Effect (VSE) has proven to be an extremely useful method to measure the local electric field using infrared spectroscopy of carbonyl and nitrile based probes. The nitrile chemical group would be an ideal choice because of its absorption in an infrared spectral window transparent to biomolecules, ease of site-specific incorporation into proteins, and common occurrence as a substituent in various drug molecules. However, the inability of VSE to describe the dependence of IR frequency on electric field for hydrogen-bonded nitriles to date has severely limited nitrile's utility to probe the noncovalent interactions. In this work, using infrared spectroscopy and atomistic molecular dynamics simulations, we have reported for the first time a linear correlation between nitrile frequencies and electric fields in a wide range of hydrogen-bonding environments that may bridge the existing gap between VSE and H-bonding interactions. We have demonstrated the robustness of this field-frequency correlation for both aromatic nitriles and sulfur-based nitriles in a wide range of molecules of varying size and compactness, including small molecules in complex solvation environments, an amino acid, disordered peptides, and structured proteins. This correlation, when coupled to VSE, can be used to quantify noncovalent interactions, specific or nonspecific, in a consistent manner.

Determination of structure and properties of molecular crystals from first principles.

PubMed

Szalewicz, Krzysztof

2014-11-18

CONSPECTUS: Until recently, it had been impossible to predict structures of molecular crystals just from the knowledge of the chemical formula for the constituent molecule(s). A solution of this problem has been achieved using intermolecular force fields computed from first principles. These fields were developed by calculating interaction energies of molecular dimers and trimers using an ab initio method called symmetry-adapted perturbation theory (SAPT) based on density-functional theory (DFT) description of monomers [SAPT(DFT)]. For clusters containing up to a dozen or so atoms, interaction energies computed using SAPT(DFT) are comparable in accuracy to the results of the best wave function-based methods, whereas the former approach can be applied to systems an order of magnitude larger than the latter. In fact, for monomers with a couple dozen atoms, SAPT(DFT) is about equally time-consuming as the supermolecular DFT approach. To develop a force field, SAPT(DFT) calculations are performed for a large number of dimer and possibly also trimer configurations (grid points in intermolecular coordinates), and the interaction energies are then fitted by analytic functions. The resulting force fields can be used to determine crystal structures and properties by applying them in molecular packing, lattice energy minimization, and molecular dynamics calculations. In this way, some of the first successful determinations of crystal structures were achieved from first principles, with crystal densities and lattice parameters agreeing with experimental values to within about 1%. Crystal properties obtained using similar procedures but empirical force fields fitted to crystal data have typical errors of several percent due to low sensitivity of empirical fits to interactions beyond those of the nearest neighbors. The first-principles approach has additional advantages over the empirical approach for notional crystals and cocrystals since empirical force fields can only be extrapolated to such cases. As an alternative to applying SAPT(DFT) in crystal structure calculations, one can use supermolecular DFT interaction energies combined with scaled dispersion energies computed from simple atom-atom functions, that is, use the so-called DFT+D approach. Whereas the standard DFT methods fail for intermolecular interactions, DFT+D performs reasonably well since the dispersion correction is used not only to provide the missing dispersion contribution but also to fix other deficiencies of DFT. The latter cancellation of errors is unphysical and can be avoided by applying the so-called dispersionless density functional, dlDF. In this case, the dispersion energies are added without any scaling. The dlDF+D method is also one of the best performing DFT+D methods. The SAPT(DFT)-based approach has been applied so far only to crystals with rigid monomers. It can be extended to partly flexible monomers, that is, to monomers with only a few internal coordinates allowed to vary. However, the costs will increase relative to rigid monomer cases since the number of grid points increases exponentially with the number of dimensions. One way around this problem is to construct force fields with approximate couplings between inter- and intramonomer degrees of freedom. Another way is to calculate interaction energies (and possibly forces) "on the fly", i.e., in each step of lattice energy minimization procedure. Such an approach would be prohibitively expensive if it replaced analytic force fields at all stages of the crystal predictions procedure, but it can be used to optimize a few dozen candidate structures determined by other methods.

Interactions between Nanoparticles and Polymer Brushes: Molecular Dynamics Simulations and Self-consistent Field Theory Calculations

NASA Astrophysics Data System (ADS)

Cheng, Shengfeng; Wen, Chengyuan; Egorov, Sergei

2015-03-01

Molecular dynamics simulations and self-consistent field theory calculations are employed to study the interactions between a nanoparticle and a polymer brush at various densities of chains grafted to a plane. Simulations with both implicit and explicit solvent are performed. In either case the nanoparticle is loaded to the brush at a constant velocity. Then a series of simulations are performed to compute the force exerted on the nanoparticle that is fixed at various distances from the grafting plane. The potential of mean force is calculated and compared to the prediction based on a self-consistent field theory. Our simulations show that the explicit solvent leads to effects that are not captured in simulations with implicit solvent, indicating the importance of including explicit solvent in molecular simulations of such systems. Our results also demonstrate an interesting correlation between the force on the nanoparticle and the density profile of the brush. We gratefully acknowledge the support of NVIDIA Corporation with the donation of the Tesla K40 GPU used for this research.

The impact of computer science in molecular medicine: enabling high-throughput research.

PubMed

de la Iglesia, Diana; García-Remesal, Miguel; de la Calle, Guillermo; Kulikowski, Casimir; Sanz, Ferran; Maojo, Víctor

2013-01-01

The Human Genome Project and the explosion of high-throughput data have transformed the areas of molecular and personalized medicine, which are producing a wide range of studies and experimental results and providing new insights for developing medical applications. Research in many interdisciplinary fields is resulting in data repositories and computational tools that support a wide diversity of tasks: genome sequencing, genome-wide association studies, analysis of genotype-phenotype interactions, drug toxicity and side effects assessment, prediction of protein interactions and diseases, development of computational models, biomarker discovery, and many others. The authors of the present paper have developed several inventories covering tools, initiatives and studies in different computational fields related to molecular medicine: medical informatics, bioinformatics, clinical informatics and nanoinformatics. With these inventories, created by mining the scientific literature, we have carried out several reviews of these fields, providing researchers with a useful framework to locate, discover, search and integrate resources. In this paper we present an analysis of the state-of-the-art as it relates to computational resources for molecular medicine, based on results compiled in our inventories, as well as results extracted from a systematic review of the literature and other scientific media. The present review is based on the impact of their related publications and the available data and software resources for molecular medicine. It aims to provide information that can be useful to support ongoing research and work to improve diagnostics and therapeutics based on molecular-level insights.

Latest advances in molecular imaging instrumentation.

PubMed

Pichler, Bernd J; Wehrl, Hans F; Judenhofer, Martin S

2008-06-01

This review concentrates on the latest advances in molecular imaging technology, including PET, MRI, and optical imaging. In PET, significant improvements in tumor detection and image resolution have been achieved by introducing new scintillation materials, iterative image reconstruction, and correction methods. These advances enabled the first clinical scanners capable of time-of-flight detection and incorporating point-spread-function reconstruction to compensate for depth-of-interaction effects. In the field of MRI, the most important developments in recent years have mainly been MRI systems with higher field strengths and improved radiofrequency coil technology. Hyperpolarized imaging, functional MRI, and MR spectroscopy provide molecular information in vivo. A special focus of this review article is multimodality imaging and, in particular, the emerging field of combined PET/MRI.

The multiscale coarse-graining method. II. Numerical implementation for coarse-grained molecular models

PubMed Central

Noid, W. G.; Liu, Pu; Wang, Yanting; Chu, Jhih-Wei; Ayton, Gary S.; Izvekov, Sergei; Andersen, Hans C.; Voth, Gregory A.

2008-01-01

The multiscale coarse-graining (MS-CG) method [S. Izvekov and G. A. Voth, J. Phys. Chem. B 109, 2469 (2005);J. Chem. Phys. 123, 134105 (2005)] employs a variational principle to determine an interaction potential for a CG model from simulations of an atomically detailed model of the same system. The companion paper proved that, if no restrictions regarding the form of the CG interaction potential are introduced and if the equilibrium distribution of the atomistic model has been adequately sampled, then the MS-CG variational principle determines the exact many-body potential of mean force (PMF) governing the equilibrium distribution of CG sites generated by the atomistic model. In practice, though, CG force fields are not completely flexible, but only include particular types of interactions between CG sites, e.g., nonbonded forces between pairs of sites. If the CG force field depends linearly on the force field parameters, then the vector valued functions that relate the CG forces to these parameters determine a set of basis vectors that span a vector subspace of CG force fields. The companion paper introduced a distance metric for the vector space of CG force fields and proved that the MS-CG variational principle determines the CG force force field that is within that vector subspace and that is closest to the force field determined by the many-body PMF. The present paper applies the MS-CG variational principle for parametrizing molecular CG force fields and derives a linear least squares problem for the parameter set determining the optimal approximation to this many-body PMF. Linear systems of equations for these CG force field parameters are derived and analyzed in terms of equilibrium structural correlation functions. Numerical calculations for a one-site CG model of methanol and a molecular CG model of the EMIM+∕NO3− ionic liquid are provided to illustrate the method. PMID:18601325

NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps

PubMed Central

2013-01-01

Background Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. Results NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. Conclusions NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps. PMID:24099179

NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps.

PubMed

Kuperstein, Inna; Cohen, David P A; Pook, Stuart; Viara, Eric; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

2013-10-07

Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps.

The study of molecular spectroscopy by ab initio methods

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.

1991-01-01

This review illustrates the potential of theory for solving spectroscopic problems. The accuracy of approximate techniques for including electron correlation have been calibrated by comparison with full configuration-interaction calculations. Examples of the application of ab initio calculations to vibrational, rotational, and electronic spectroscopy are given. It is shown that the state-averaged, complete active space self-consistent field, multireference configuration-interaction procedure provides a good approach for treating several electronic states accurately in a common molecular orbital basis.

The effect of side motion in the dynamics of interacting molecular motors

NASA Astrophysics Data System (ADS)

Midha, Tripti; Gupta, Arvind Kumar; Kolomeisky, Anatoly B.

2017-07-01

To mimic the collective motion of interacting molecular motors, we propose and discuss an open two-lane symmetrically coupled interactive TASEP model that incorporates interaction in the thermodynamically consistent fashion. We study the effect of both repulsive and attractive interaction on the system’s dynamical properties using various cluster mean field analysis and extensive Monte Carlo simulations. The interactions bring correlations into the system, which were found to be reduced due to the side motion of particles. We produce the steady-state phase diagrams for symmetrically split interaction strength. The behavior of the maximal particle current with respect to the interaction energy E is analyzed for different coupling rates and interaction splittings. The results suggest that for strong coupling and large splittings, the maximal flow of the motors occurs at a weak attractive interaction strength which matches with the known experimental results on kinesin motor protein.

Molecularly Imprinted Polymers: Present and Future Prospective

PubMed Central

Vasapollo, Giuseppe; Sole, Roberta Del; Mergola, Lucia; Lazzoi, Maria Rosaria; Scardino, Anna; Scorrano, Sonia; Mele, Giuseppe

2011-01-01

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented. PMID:22016636

Reparameterization of Solute—Solute Interactions for Amino Acid-Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations

PubMed Central

Lay, Wesley K.; Miller, Mark S.

2018-01-01

AMBER/GLYCAM and CHARMM are popular force fields for simulations of amino acids and sugars. Here we report excessively attractive amino acid-sugar interactions in both force fields, and corrections to nonbonded interactions that match experimental osmotic pressures of mixed aqueous solutions of diglycine and sucrose. The modified parameters also improve the ΔGtrans of diglycine from water to aqueous sucrose and, with AMBERff99SB/GLYCAM06, eliminate a caging effect seen in previous simulations of the protein ubiquitin with glucose. PMID:28437100

Dark-field-based observation of single-nanoparticle dynamics on a supported lipid bilayer for in situ analysis of interacting molecules and nanoparticles.

PubMed

Lee, Young Kwang; Kim, Sungi; Nam, Jwa-Min

2015-01-12

Observation of single plasmonic nanoparticles in reconstituted biological systems allows us to obtain snapshots of dynamic processes between molecules and nanoparticles with unprecedented spatiotemporal resolution and single-molecule/single-particle-level data acquisition. This Concept is intended to introduce nanoparticle-tethered supported lipid bilayer platforms that allow for the dynamic confinement of nanoparticles on a two-dimensional fluidic surface. The dark-field-based long-term, stable, real-time observation of freely diffusing plasmonic nanoparticles on a lipid bilayer enables one to extract a broad range of information about interparticle and molecular interactions throughout the entire reaction period. Herein, we highlight important developments in this context to provide ideas on how molecular interactions can be interpreted by monitoring dynamic behaviors and optical signals of laterally mobile nanoparticles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors

NASA Astrophysics Data System (ADS)

Johann, D.; Goswami, D.; Kruse, K.

2016-06-01

During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.

Proposed alteration of images of molecular orbitals obtained using a scanning tunneling microscope as a probe of electron correlation.

PubMed

Toroz, Dimitrios; Rontani, Massimo; Corni, Stefano

2013-01-04

Scanning tunneling spectroscopy (STS) allows us to image single molecules decoupled from the supporting substrate. The obtained images are routinely interpreted as the square moduli of molecular orbitals, dressed by the mean-field electron-electron interaction. Here we demonstrate that the effect of electron correlation beyond the mean field qualitatively alters the uncorrelated STS images. Our evidence is based on the ab initio many-body calculation of STS images of planar molecules with metal centers. We find that many-body correlations alter significantly the image spectral weight close to the metal center of the molecules. This change is large enough to be accessed experimentally, surviving to molecule-substrate interactions.

Rigorous theory of molecular orientational nonlinear optics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwak, Chong Hoon, E-mail: chkwak@ynu.ac.kr; Kim, Gun Yeup

2015-01-15

Classical statistical mechanics of the molecular optics theory proposed by Buckingham [A. D. Buckingham and J. A. Pople, Proc. Phys. Soc. A 68, 905 (1955)] has been extended to describe the field induced molecular orientational polarization effects on nonlinear optics. In this paper, we present the generalized molecular orientational nonlinear optical processes (MONLO) through the calculation of the classical orientational averaging using the Boltzmann type time-averaged orientational interaction energy in the randomly oriented molecular system under the influence of applied electric fields. The focal points of the calculation are (1) the derivation of rigorous tensorial components of the effective molecularmore » hyperpolarizabilities, (2) the molecular orientational polarizations and the electronic polarizations including the well-known third-order dc polarization, dc electric field induced Kerr effect (dc Kerr effect), optical Kerr effect (OKE), dc electric field induced second harmonic generation (EFISH), degenerate four wave mixing (DFWM) and third harmonic generation (THG). We also present some of the new predictive MONLO processes. For second-order MONLO, second-order optical rectification (SOR), Pockels effect and difference frequency generation (DFG) are described in terms of the anisotropic coefficients of first hyperpolarizability. And, for third-order MONLO, third-order optical rectification (TOR), dc electric field induced difference frequency generation (EFIDFG) and pump-probe transmission are presented.« less

Molecular dynamics simulations for mechanical properties of borophene: parameterization of valence force field model and Stillinger-Weber potential

PubMed Central

Zhou, Yu-Ping; Jiang, Jin-Wu

2017-01-01

While most existing theoretical studies on the borophene are based on first-principles calculations, the present work presents molecular dynamics simulations for the lattice dynamical and mechanical properties in borophene. The obtained mechanical quantities are in good agreement with previous first-principles calculations. The key ingredients for these molecular dynamics simulations are the two efficient empirical potentials developed in the present work for the interaction of borophene with low-energy triangular structure. The first one is the valence force field model, which is developed with the assistance of the phonon dispersion of borophene. The valence force field model is a linear potential, so it is rather efficient for the calculation of linear quantities in borophene. The second one is the Stillinger-Weber potential, whose parameters are derived based on the valence force field model. The Stillinger-Weber potential is applicable in molecular dynamics simulations of nonlinear physical or mechanical quantities in borophene. PMID:28349983

How well do force fields capture the strength of salt bridges in proteins?

PubMed Central

Ahmed, Mustapha Carab; Papaleo, Elena

2018-01-01

Salt bridges form between pairs of ionisable residues in close proximity and are important interactions in proteins. While salt bridges are known to be important both for protein stability, recognition and regulation, we still do not have fully accurate predictive models to assess the energetic contributions of salt bridges. Molecular dynamics simulation is one technique that may be used study the complex relationship between structure, solvation and energetics of salt bridges, but the accuracy of such simulations depends on the force field used. We have used NMR data on the B1 domain of protein G (GB1) to benchmark molecular dynamics simulations. Using enhanced sampling simulations, we calculated the free energy of forming a salt bridge for three possible lysine-carboxylate ionic interactions in GB1. The NMR experiments showed that these interactions are either not formed, or only very weakly formed, in solution. In contrast, we show that the stability of the salt bridges is overestimated, to different extents, in simulations of GB1 using seven out of eight commonly used combinations of fixed charge force fields and water models. We also find that the Amber ff15ipq force field gives rise to weaker salt bridges in good agreement with the NMR experiments. We conclude that many force fields appear to overstabilize these ionic interactions, and that further work may be needed to refine our ability to model quantitatively the stability of salt bridges through simulations. We also suggest that comparisons between NMR experiments and simulations will play a crucial role in furthering our understanding of this important interaction.

Fixed-Charge Atomistic Force Fields for Molecular Dynamics Simulations in the Condensed Phase: An Overview.

PubMed

Riniker, Sereina

2018-03-26

In molecular dynamics or Monte Carlo simulations, the interactions between the particles (atoms) in the system are described by a so-called force field. The empirical functional form of classical fixed-charge force fields dates back to 1969 and remains essentially unchanged. In a fixed-charge force field, the polarization is not modeled explicitly, i.e. the effective partial charges do not change depending on conformation and environment. This simplification allows, however, a dramatic reduction in computational cost compared to polarizable force fields and in particular quantum-chemical modeling. The past decades have shown that simulations employing carefully parametrized fixed-charge force fields can provide useful insights into biological and chemical questions. This overview focuses on the four major force-field families, i.e. AMBER, CHARMM, GROMOS, and OPLS, which are based on the same classical functional form and are continuously improved to the present day. The overview is aimed at readers entering the field of (bio)molecular simulations. More experienced users may find the comparison and historical development of the force-field families interesting.

Evaluation of reactive force fields for prediction of the thermo-mechanical properties of cellulose Iâ

Treesearch

Fernando L. Dri; Xiawa Wu; Robert J. Moon; Ashlie Martini; Pablo D. Zavattieri

2015-01-01

Molecular dynamics simulation is commonly used to study the properties of nanocellulose-based materials at the atomic scale. It is well known that the accuracy of these simulations strongly depends on the force field that describes energetic interactions. However, since there is no force field developed specifically for cellulose, researchers utilize models...

Investigation of antigen-antibody interactions of sulfonamides with a monoclonal antibody in a fluorescence polarization immunoassay using 3D-QSAR models

USDA-ARS?s Scientific Manuscript database

A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular si...

Active molecular plasmonics: tuning surface plasmon resonances by exploiting molecular dimensions

NASA Astrophysics Data System (ADS)

Chen, Kai; Leong, Eunice Sok Ping; Rukavina, Michael; Nagao, Tadaaki; Liu, Yan Jun; Zheng, Yuebing

2015-06-01

Molecular plasmonics explores and exploits the molecule-plasmon interactions on metal nanostructures to harness light at the nanoscale for nanophotonic spectroscopy and devices. With the functional molecules and polymers that change their structural, electrical, and/or optical properties in response to external stimuli such as electric fields and light, one can dynamically tune the plasmonic properties for enhanced or new applications, leading to a new research area known as active molecular plasmonics (AMP). Recent progress in molecular design, tailored synthesis, and self-assembly has enabled a variety of scenarios of plasmonic tuning for a broad range of AMP applications. Dimension (i.e., zero-, two-, and threedimensional) of the molecules on metal nanostructures has proved to be an effective indicator for defining the specific scenarios. In this review article, we focus on structuring the field of AMP based on the dimension of molecules and discussing the state of the art of AMP. Our perspective on the upcoming challenges and opportunities in the emerging field of AMP is also included.

Computer-aided molecular modeling techniques for predicting the stability of drug cyclodextrin inclusion complexes in aqueous solutions

NASA Astrophysics Data System (ADS)

Faucci, Maria Teresa; Melani, Fabrizio; Mura, Paola

2002-06-01

Molecular modeling was used to investigate factors influencing complex formation between cyclodextrins and guest molecules and predict their stability through a theoretical model based on the search for a correlation between experimental stability constants ( Ks) and some theoretical parameters describing complexation (docking energy, host-guest contact surfaces, intermolecular interaction fields) calculated from complex structures at a minimum conformational energy, obtained through stochastic methods based on molecular dynamic simulations. Naproxen, ibuprofen, ketoprofen and ibuproxam were used as model drug molecules. Multiple Regression Analysis allowed identification of the significant factors for the complex stability. A mathematical model ( r=0.897) related log Ks with complex docking energy and lipophilic molecular fields of cyclodextrin and drug.

MOLSIM: A modular molecular simulation software

PubMed Central

Jurij, Reščič

2015-01-01

The modular software MOLSIM for all‐atom molecular and coarse‐grained simulations is presented with focus on the underlying concepts used. The software possesses four unique features: (1) it is an integrated software for molecular dynamic, Monte Carlo, and Brownian dynamics simulations; (2) simulated objects are constructed in a hierarchical fashion representing atoms, rigid molecules and colloids, flexible chains, hierarchical polymers, and cross‐linked networks; (3) long‐range interactions involving charges, dipoles and/or anisotropic dipole polarizabilities are handled either with the standard Ewald sum, the smooth particle mesh Ewald sum, or the reaction‐field technique; (4) statistical uncertainties are provided for all calculated observables. In addition, MOLSIM supports various statistical ensembles, and several types of simulation cells and boundary conditions are available. Intermolecular interactions comprise tabulated pairwise potentials for speed and uniformity and many‐body interactions involve anisotropic polarizabilities. Intramolecular interactions include bond, angle, and crosslink potentials. A very large set of analyses of static and dynamic properties is provided. The capability of MOLSIM can be extended by user‐providing routines controlling, for example, start conditions, intermolecular potentials, and analyses. An extensive set of case studies in the field of soft matter is presented covering colloids, polymers, and crosslinked networks. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:25994597

Model Hamiltonian Calculations of the Nonlinear Polarizabilities of Conjugated Molecules.

NASA Astrophysics Data System (ADS)

Risser, Steven Michael

This dissertation advances the theoretical knowledge of the nonlinear polarizabilities of conjugated molecules. The unifying feature of these molecules is an extended delocalized pi electron structure. The pi electrons dominate the electronic properties of the molecules, allowing prediction of molecular properties based on the treatment of just the pi electrons. Two separate pi electron Hamiltonians are used in the research. The principal Hamiltonian used is the non-interacting single-particle Huckel Hamiltonian, which replaces the Coulomb interaction among the pi electrons with a mean field interaction. The simplification allows for exact solution of the Hamiltonian for large molecules. The second Hamiltonian used for this research is the interacting multi-particle Pariser-Parr-Pople (PPP) Hamiltonian, which retains explicit Coulomb interactions. This limits exact solutions to molecules containing at most eight electrons. The molecular properties being investigated are the linear polarizability, and the second and third order hyperpolarizabilities. The hyperpolarizabilities determine the nonlinear optical response of materials. These molecular parameters are determined by two independent approaches. The results from the Huckel Hamiltonian are obtained through first, second and third order perturbation theory. The results from the PPP Hamiltonian are obtained by including the applied field directly in the Hamiltonian and determining the ground state energy at a series of field strengths. By fitting the energy to a polynomial in field strength, the polarizability and hyperpolarizabilities are determined. The Huckel Hamiltonian is used to calculate the third order hyperpolarizability of polyenes. These calculations were the first to show the average hyperpolarizability of the polyenes to be positive, and also to show the saturation of the hyperpolarizability. Comparison of these Huckel results to those from the PPP Hamiltonian shows the lack of explicit Coulomb interactions in the Huckel Hamiltonian results in calculated hyperpolarizabilities that are much larger than the experimentally determined values. Comparison of hyperpolarizabilities calculated for small benzene derivatives using both the Huckel and PPP Hamiltonians shows that inclusion of explicit Coulomb interactions is not as significant for aromatic molecules. This assertion is supported by comparison of the calculated results to the experimentally determined values. This allows for predictions of the hyperpolarizability of various liquid crystal molecules to be made.

Dynamics of plasmonic field polarization induced by quantum coherence in quantum dot-metallic nanoshell structures.

PubMed

Sadeghi, S M

2014-09-01

When a hybrid system consisting of a semiconductor quantum dot and a metallic nanoparticle interacts with a laser field, the plasmonic field of the metallic nanoparticle can be normalized by the quantum coherence generated in the quantum dot. In this Letter, we study the states of polarization of such a coherent-plasmonic field and demonstrate how these states can reveal unique aspects of the collective molecular properties of the hybrid system formed via coherent exciton-plasmon coupling. We show that transition between the molecular states of this system can lead to ultrafast polarization dynamics, including sudden reversal of the sense of variations of the plasmonic field and formation of circular and elliptical polarization.

Molecular simulation of the thermophysical properties and phase behaviour of impure CO2 relevant to CCS.

PubMed

Cresswell, Alexander J; Wheatley, Richard J; Wilkinson, Richard D; Graham, Richard S

2016-10-20

Impurities from the CCS chain can greatly influence the physical properties of CO 2 . This has important design, safety and cost implications for the compression, transport and storage of CO 2 . There is an urgent need to understand and predict the properties of impure CO 2 to assist with CCS implementation. However, CCS presents demanding modelling requirements. A suitable model must both accurately and robustly predict CO 2 phase behaviour over a wide range of temperatures and pressures, and maintain that predictive power for CO 2 mixtures with numerous, mutually interacting chemical species. A promising technique to address this task is molecular simulation. It offers a molecular approach, with foundations in firmly established physical principles, along with the potential to predict the wide range of physical properties required for CCS. The quality of predictions from molecular simulation depends on accurate force-fields to describe the interactions between CO 2 and other molecules. Unfortunately, there is currently no universally applicable method to obtain force-fields suitable for molecular simulation. In this paper we present two methods of obtaining force-fields: the first being semi-empirical and the second using ab initio quantum-chemical calculations. In the first approach we optimise the impurity force-field against measurements of the phase and pressure-volume behaviour of CO 2 binary mixtures with N 2 , O 2 , Ar and H 2 . A gradient-free optimiser allows us to use the simulation itself as the underlying model. This leads to accurate and robust predictions under conditions relevant to CCS. In the second approach we use quantum-chemical calculations to produce ab initio evaluations of the interactions between CO 2 and relevant impurities, taking N 2 as an exemplar. We use a modest number of these calculations to train a machine-learning algorithm, known as a Gaussian process, to describe these data. The resulting model is then able to accurately predict a much broader set of ab initio force-field calculations at comparatively low numerical cost. Although our method is not yet ready to be implemented in a molecular simulation, we outline the necessary steps here. Such simulations have the potential to deliver first-principles simulation of the thermodynamic properties of impure CO 2 , without fitting to experimental data.

Computing by physical interaction in neurons.

PubMed

Aur, Dorian; Jog, Mandar; Poznanski, Roman R

2011-12-01

The electrodynamics of action potentials represents the fundamental level where information is integrated and processed in neurons. The Hodgkin-Huxley model cannot explain the non-stereotyped spatial charge density dynamics that occur during action potential propagation. Revealed in experiments as spike directivity, the non-uniform charge density dynamics within neurons carry meaningful information and suggest that fragments of information regarding our memories are endogenously stored in structural patterns at a molecular level and are revealed only during spiking activity. The main conceptual idea is that under the influence of electric fields, efficient computation by interaction occurs between charge densities embedded within molecular structures and the transient developed flow of electrical charges. This process of computation underlying electrical interactions and molecular mechanisms at the subcellular level is dissimilar from spiking neuron models that are completely devoid of physical interactions. Computation by interaction describes a more powerful continuous model of computation than the one that consists of discrete steps as represented in Turing machines.

Structural Interface Parameters Are Discriminatory in Recognising Near-Native Poses of Protein-Protein Interactions

PubMed Central

Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

2014-01-01

Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets. PMID:24498255

Structural interface parameters are discriminatory in recognising near-native poses of protein-protein interactions.

PubMed

Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

2014-01-01

Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets.

Simulation of carbohydrates, from molecular docking to dynamics in water.

PubMed

Sapay, Nicolas; Nurisso, Alessandra; Imberty, Anne

2013-01-01

Modeling of carbohydrates is particularly challenging because of the variety of structures resulting for the high number of monosaccharides and possible linkages and also because of their intrinsic flexibility. The development of carbohydrate parameters for molecular modeling is still an active field. Nowadays, main carbohydrates force fields are GLYCAM06, CHARMM36, and GROMOS 45A4. GLYCAM06 includes the largest choice of compounds and is compatible with the AMBER force fields and associated. Furthermore, AMBER includes tools for the implementation of new parameters. When looking at protein-carbohydrate interaction, the choice of the starting structure is of importance. Such complex can be sometimes obtained from the Protein Data Bank-although the stereochemistry of sugars may require some corrections. When no experimental data is available, molecular docking simulation is generally used to the obtain protein-carbohydrate complex coordinates. As molecular docking parameters are not specifically dedicated to carbohydrates, inaccuracies should be expected, especially for the docking of polysaccharides. This issue can be addressed at least partially by combining molecular docking with molecular dynamics simulation in water.

Probing Silica-Biomolecule Interactions by Solid-State NMR and Molecular Dynamics Simulations.

PubMed

Brückner, Stephan Ingmar; Donets, Sergii; Dianat, Arezoo; Bobeth, Manfred; Gutiérrez, Rafael; Cuniberti, Gianaurelio; Brunner, Eike

2016-11-08

Understanding the molecular interactions between inorganic phases such as silica and organic material is fundamental for chromatographic applications, for tailoring silica-enzyme interactions, and for elucidating the mechanisms of biomineralization. The formation, structure, and properties of the organic/inorganic interface is crucial in this context. Here, we investigate the interaction of selectively 13 C-labeled choline with 29 Si-labeled monosilicic acid/silica at the molecular level. Silica/choline nanocomposites were analyzed by solid-state NMR spectroscopy in combination with extended molecular dynamics (MD) simulations to understand the silica/organic interface. Cross-polarization magic angle spinning (CP MAS)-based NMR experiments like 1 H- 13 C CP-REDOR (rotational-echo double resonance), 1 H- 13 C HETCOR (heteronuclear correlation), and 1 H- 29 Si- 1 H double CP are employed to determine spatial parameters. The measurement of 29 Si- 13 C internuclear distances for selectively 13 C-labeled choline provides an experimental parameter that allows the direct verification of MD simulations. Atomistic modeling using classical MD methodologies is performed using the INTERFACE force field. The modeling results are in excellent agreement with the experimental data and reveal the relevant molecular conformations as well as the nature and interplay of the interactions between the choline cation and the silica surface. Electrostatic interactions and hydrogen bonding are both important and depend strongly on the hydration level as well as the charge state of the silica surface.

Molecular and ionic diffusion in aqueous - deep eutectic solvent mixtures: probing inter-molecular interactions using PFG NMR.

PubMed

D'Agostino, Carmine; Gladden, Lynn F; Mantle, Mick D; Abbott, Andrew P; Ahmed, Essa I; Al-Murshedi, Azhar Y M; Harris, Robert C

2015-06-21

Pulsed field gradient (PFG) NMR has been used to probe self-diffusion of molecular and ionic species in aqueous mixtures of choline chloride (ChCl) based deep eutectic solvents (DESs), in order to elucidate the effect of water on motion and inter-molecular interactions between the different species in the mixtures, namely the Ch(+) cation and hydrogen bond donor (HBD). The results reveal an interesting and complex behaviour of such mixtures at a molecular level. In general, it is observed that the hydroxyl protons ((1)H) of Ch(+) and the hydrogen bond donor have diffusion coefficients significantly different from those measured for their parent molecules when water is added. This indicates a clear and significant change in inter-molecular interactions. In aqueous Ethaline, the hydroxyl species of Ch(+) and HBD show a stronger interaction with water as water is added to the system. In the case of Glyceline, water has little effect on both hydroxyl proton diffusion of Ch(+) and HBD. In Reline, it is likely that water allows the formation of small amounts of ammonium hydroxide. The most surprising observation is from the self-diffusion of water, which is considerably higher that expected from a homogeneous liquid. This leads to the conclusion that Reline and Glyceline form mixtures that are inhomogeneous at a microscopic level despite the hydrophilicity of the salt and HBD. This work shows that PFG NMR is a powerful tool to elucidate both molecular dynamics and inter-molecular interactions in complex liquid mixtures, such as the aqueous DES mixtures.

Modulating the Electron-Hole Interaction in a Hybrid Lead Halide Perovskite with an Electric Field.

PubMed

Leijtens, Tomas; Srimath Kandada, Ajay Ram; Eperon, Giles E; Grancini, Giulia; D'Innocenzo, Valerio; Ball, James M; Stranks, Samuel D; Snaith, Henry J; Petrozza, Annamaria

2015-12-16

Despite rapid developments in both photovoltaic and light-emitting device performance, the understanding of the optoelectronic properties of hybrid lead halide perovskites is still incomplete. In particular, the polarizability of the material, the presence of molecular dipoles, and their influence on the dynamics of the photoexcitations remain an open issue to be clarified. Here, we investigate the effect of an applied external electric field on the photoexcited species of CH3NH3PbI3 thin films, both at room temperature and at low temperature, by monitoring the photoluminescence (PL) yield and PL decays. At room temperature we find evidence for electric-field-induced reduction of radiative bimolecular carrier recombination together with motion of charged defects that affects the nonradiative decay rate of the photoexcited species. At low temperature (190 K), we observe a field-induced enhancement of radiative free carrier recombination rates that lasts even after the removal of the field. We assign this to field-induced alignment of the molecular dipoles, which reduces the vibrational freedom of the lattice and the associated local screening and hence results in a stronger electron-hole interaction.

Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.

PubMed

Thillainayagam, Mahalakshmi; Anbarasu, Anand; Ramaiah, Sudha

2016-08-21

The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bacterial Chemotaxis: The Early Years of Molecular Studies

PubMed Central

Hazelbauer, Gerald L.

2014-01-01

This review focuses on the early years of molecular studies of bacterial chemotaxis and motility, beginning in the 1960s with Julius Adler's pioneering work. It describes key observations that established the field and made bacterial chemotaxis a paradigm for the molecular understanding of biological signaling. Consideration of those early years includes aspects of science seldom described in journals: the accidental findings, personal interactions, and scientific culture that often drive scientific progress. PMID:22994495

Cs 62 DJ Rydberg-atom macrodimers formed by long-range multipole interaction

NASA Astrophysics Data System (ADS)

Han, Xiaoxuan; Bai, Suying; Jiao, Yuechun; Hao, Liping; Xue, Yongmei; Zhao, Jianming; Jia, Suotang; Raithel, Georg

2018-03-01

Long-range macrodimers formed by D -state cesium Rydberg atoms are studied in experiments and calculations. Cesium [62DJ]2 Rydberg-atom macrodimers, bonded via long-range multipole interaction, are prepared by two-color photoassociation in a cesium atom trap. The first color (pulse A) resonantly excites seed Rydberg atoms, while the second (pulse B, detuned by the molecular binding energy) resonantly excites the Rydberg-atom macrodimers below the [62DJ]2 asymptotes. The molecules are measured by extraction of autoionization products and Rydberg-atom electric-field ionization, and ion detection. Molecular spectra are compared with calculations of adiabatic molecular potentials. From the dependence of the molecular signal on the detection delay time, the lifetime of the molecules is estimated to be 3 -6 μ s .

Ion optical design of a collinear laser-negative ion beam apparatus.

PubMed

Diehl, C; Wendt, K; Lindahl, A O; Andersson, P; Hanstorp, D

2011-05-01

An apparatus for photodetachment studies on atomic and molecular negative ions of medium up to heavy mass (M ≃ 500) has been designed and constructed. Laser and ion beams are merged in the apparatus in a collinear geometry and atoms, neutral molecules and negative ions are detected in the forward direction. The ion optical design and the components used to optimize the mass resolution and the transmission through the extended field-free interaction region are described. A 90° sector field magnet with 50 cm bending radius in combination with two slits is used for mass dispersion providing a resolution of M∕ΔM≅800 for molecular ions and M∕ΔM≅400 for atomic ions. The difference in mass resolution for atomic and molecular ions is attributed to different energy distributions of the sputtered ions. With 1 mm slits, transmission from the source through the interaction region to the final ion detector was determined to be about 0.14%.

Enhancement of linear/nonlinear optical responses of molecular vibrations using metal nanoantennas

NASA Astrophysics Data System (ADS)

Morichika, Ikki; Kusa, Fumiya; Takegami, Akinobu; Ashihara, Satoshi

2017-04-01

Plasmonic enhancements of optical near-fields with metal nanostructures offer extensive potential for amplifying lightmatter interactions. We analytically formulate the enhancement of linear and nonlinear optical responses of molecular vibrations through resonant nanoantennas, based on a coupled-dipole model. We apply the formulae to evaluation of signal enhancement factors in the antenna-enhanced vibrational spectroscopy.

Gas-liquid coexistence in a system of dipolar soft spheres.

PubMed

Jia, Ran; Braun, Heiko; Hentschke, Reinhard

2010-12-01

The existence of gas-liquid coexistence in dipolar fluids with no other contribution to attractive interaction than dipole-dipole interaction is a basic and open question in the theory of fluids. Here we compute the gas-liquid critical point in a system of dipolar soft spheres subject to an external electric field using molecular dynamics computer simulation. Tracking the critical point as the field strength is approaching zero we find the following limiting values: T(c)=0.063 and ρ(c)=0.0033 (dipole moment μ=1). These values are confirmed by independent simulation at zero field strength.

Host and adsorbate dynamics in silicates with flexible frameworks: Empirical force field simulation of water in silicalite

NASA Astrophysics Data System (ADS)

Bordat, Patrice; Cazade, Pierre-André; Baraille, Isabelle; Brown, Ross

2010-03-01

Molecular dynamics simulations are performed on the pure silica zeolite silicalite (MFI framework code), maintaining via a new force field both framework flexibility and realistic account of electrostatic interactions with adsorbed water. The force field is similar to the well-known "BKS" model [B. W. H. van Beest et al., Phys. Rev. Lett. 64, 1955 (1990)], but with reduced partial atomic charges and reoptimized covalent bond potential wells. The present force field reproduces the monoclinic to orthorhombic transition of silicalite. The force field correctly represents the hydrophobicity of pure silica silicalite, both the adsorption energy, and the molecular diffusion constants of water. Two types of adsorption, specific and weak unspecific, are predicted on the channel walls and at the channel intersection. We discuss molecular diffusion of water in silicalite, deducing a barrier to crossing between the straight and the zigzag channels. Analysis of the thermal motion shows that at room temperature, framework oxygen atoms incurring into the zeolite channels significantly influence the dynamics of adsorbed water.

A cohesive-frictional force field (CFFF) for colloidal calcium-silicate-hydrates

NASA Astrophysics Data System (ADS)

Palkovic, Steven D.; Yip, Sidney; Büyüköztürk, Oral

2017-12-01

Calcium-silicate-hydrate (C-S-H) gel is a cohesive-frictional material that exhibits strength asymmetry in compression and tension and normal-stress dependency of the maximum shear strength. Experiments suggest the basic structural component of C-S-H is a colloidal particle with an internal layered structure. These colloids form heterogeneous assemblies with a complex pore network at the mesoscale. We propose a cohesive-frictional force field (CFFF) to describe the interactions in colloidal C-S-H materials that incorporates the strength anisotropy fundamental to the C-S-H molecular structure that has been omitted from recent mesoscale models. We parameterize the CFFF from reactive force field simulations of an internal interface that controls mechanical performance, describing the behavior of thousands of atoms through a single effective pair interaction. We apply the CFFF to study the mesoscale elastic and Mohr-Coulomb strength properties of C-S-H with varying polydispersity and packing density. Our results show that the consideration of cohesive-frictional interactions lead to an increase in stiffness, shear strength, and normal-stress dependency, while also changing the nature of local deformation processes. The CFFF and our coarse-graining approach provide an essential connection between nanoscale molecular interactions and macroscale continuum behavior for hydrated cementitious materials.

Calculations of the free energy of interaction of the c-Fos-c-Jun coiled coil: effects of the solvation model and the inclusion of polarization effects.

PubMed

Zuo, Zhili; Gandhi, Neha S; Mancera, Ricardo L

2010-12-27

The leucine zipper region of activator protein-1 (AP-1) comprises the c-Jun and c-Fos proteins and constitutes a well-known coiled coil protein-protein interaction motif. We have used molecular dynamics (MD) simulations in conjunction with the molecular mechanics/Poisson-Boltzmann generalized-Born surface area [MM/PB(GB)SA] methods to predict the free energy of interaction of these proteins. In particular, the influence of the choice of solvation model, protein force field, and water potential on the stability and dynamic properties of the c-Fos-c-Jun complex were investigated. Use of the AMBER polarizable force field ff02 in combination with the polarizable POL3 water potential was found to result in increased stability of the c-Fos-c-Jun complex. MM/PB(GB)SA calculations revealed that MD simulations using the POL3 water potential give the lowest predicted free energies of interaction compared to other nonpolarizable water potentials. In addition, the calculated absolute free energy of binding was predicted to be closest to the experimental value using the MM/GBSA method with independent MD simulation trajectories using the POL3 water potential and the polarizable ff02 force field, while all other binding affinities were overestimated.

Transferability of polarizable models for ion-water electrostatic interaction

NASA Astrophysics Data System (ADS)

Masia, Marco

2009-06-01

Studies of ion-water systems at condensed phase and at interfaces have pointed out that molecular and ionic polarization plays an important role for many phenomena ranging from hydrogen bond dynamics to water interfaces' structure. Classical and ab initio Molecular Dynamics simulations reveal that induced dipole moments at interfaces (e.g. air-water and water-protein) are usually high, hinting that polarizable models to be implemented in classical force fields should be very accurate in reproducing the electrostatic properties of the system. In this paper the electrostatic properties of three classical polarizable models for ion-water interaction are compared with ab initio results both at gas and condensed phase. For Li+- water and Cl--water dimers the reproducibility of total dipole moments obtained with high level quantum chemical calculations is studied; for the same ions in liquid water, Car-Parrinello Molecular Dynamics simulations are used to compute the time evolution of ionic and molecular dipole moments, which are compared with the classical models. The PD2-H2O model developed by the author and coworkers [Masia et al. J. Chem. Phys. 2004, 121, 7362] together with the gaussian intermolecular damping for ion-water interaction [Masia et al. J. Chem. Phys. 2005, 123, 164505] showed to be the fittest in reproducing the ab initio results from gas to condensed phase, allowing for force field transferability.

Precise measurement of the self-diffusion coefficient for poly(ethylene glycol) in aqueous solution using uniform oligomers

NASA Astrophysics Data System (ADS)

Shimada, Kayori; Kato, Haruhisa; Saito, Takeshi; Matsuyama, Shigetomo; Kinugasa, Shinichi

2005-06-01

Uniform poly(ethylene glycol) (PEG) oligomers, with a degree of polymerization n =1-40, were separated by preparative supercritical fluid chromatography from commercial monodispersed samples. Diffusion coefficients, D, for separated uniform PEG oligomers were measured in dilute solutions of deuterium oxide (D2O) at 30 ° C, using pulsed-field gradient nuclear magnetic resonance. The measured D for each molecular weight was extrapolated to infinite dilution. Diffusion coefficients obtained at infinite dilution follow the scaling behavior of Zimm-type diffusion, even in the lower molecular weight range. Molecular-dynamics simulations for PEG in H2O also showed this scaling behavior, and reproduced close hydrodynamic interactions between PEG and water. These findings suggest that diffusion of PEG in water is dominated by hydrodynamic interaction over a wide molecular weight range, including at low molecular weights around 1000.

Nonadiabatic Ab Initio Molecular Dynamics with the Floating Occupation Molecular Orbital-Complete Active Space Configuration Interaction Method [Non-Adiabatic Ab Initio Molecular Dynamics with Floating Occupation Molecular Orbitals CASCI Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hollas, Daniel; Sistik, Lukas; Hohenstein, Edward G.

Here, we show that the floating occupation molecular orbital complete active space configuration interaction (FOMO-CASCI) method is a promising alternative to the widely used complete active space self-consistent field (CASSCF) method in direct nonadiabatic dynamics simulations. We have simulated photodynamics of three archetypal molecules in photodynamics: ethylene, methaniminium cation, and malonaldehyde. We compared the time evolution of electronic populations and reaction mechanisms as revealed by the FOMO-CASCI and CASSCF approaches. Generally, the two approaches provide similar results. Some dynamical differences are observed, but these can be traced back to energetically minor differences in the potential energy surfaces. We suggest thatmore » the FOMO-CASCI method represents, due to its efficiency and stability, a promising approach for direct ab initio dynamics in the excited state.« less

Modelling of particle-laden flow inside nanomaterials.

PubMed

Chan, Yue; Wylie, Jonathan J; Xia, Liang; Ren, Yong; Chen, Yung-Tsang

2016-08-01

In this paper, we demonstrate the usage of the Nernst-Planck equation in conjunction with mean-field theory to investigate particle-laden flow inside nanomaterials. Most theoretical studies in molecular encapsulation at the nanoscale do not take into account any macroscopic flow fields that are crucial in squeezing molecules into nanostructures. Here, a multi-scale idea is used to address this issue. The macroscopic transport of gas is described by the Nernst-Planck equation, whereas molecular interactions between gases and between the gas and the host material are described using a combination of molecular dynamics simulation and mean-field theory. In particular, we investigate flow-driven hydrogen storage inside doubly layered graphene sheets and graphene-oxide frameworks (GOFs). At room temperature and with slow velocity fields, we find that a single molecular layer is formed almost instantaneously on the inner surface of the graphene sheets, while molecular ligands between GOFs induce multi-layers. For higher velocities, multi-layers are also formed between graphene. For even larger velocities, the cavity of graphene is filled entirely with hydrogen, whereas for GOFs there exist two voids inside each periodic unit. The flow-driven hydrogen storage inside GOFs with various ligand densities is also investigated.

Modelling of particle-laden flow inside nanomaterials

NASA Astrophysics Data System (ADS)

Chan, Yue; Wylie, Jonathan J.; Xia, Liang; Ren, Yong; Chen, Yung-Tsang

2016-08-01

In this paper, we demonstrate the usage of the Nernst-Planck equation in conjunction with mean-field theory to investigate particle-laden flow inside nanomaterials. Most theoretical studies in molecular encapsulation at the nanoscale do not take into account any macroscopic flow fields that are crucial in squeezing molecules into nanostructures. Here, a multi-scale idea is used to address this issue. The macroscopic transport of gas is described by the Nernst-Planck equation, whereas molecular interactions between gases and between the gas and the host material are described using a combination of molecular dynamics simulation and mean-field theory. In particular, we investigate flow-driven hydrogen storage inside doubly layered graphene sheets and graphene-oxide frameworks (GOFs). At room temperature and with slow velocity fields, we find that a single molecular layer is formed almost instantaneously on the inner surface of the graphene sheets, while molecular ligands between GOFs induce multi-layers. For higher velocities, multi-layers are also formed between graphene. For even larger velocities, the cavity of graphene is filled entirely with hydrogen, whereas for GOFs there exist two voids inside each periodic unit. The flow-driven hydrogen storage inside GOFs with various ligand densities is also investigated.

Accurate thermodynamics for short-ranged truncations of Coulomb interactions in site-site molecular models

NASA Astrophysics Data System (ADS)

Rodgers, Jocelyn M.; Weeks, John D.

2009-12-01

Coulomb interactions are present in a wide variety of all-atom force fields. Spherical truncations of these interactions permit fast simulations but are problematic due to their incorrect thermodynamics. Herein we demonstrate that simple analytical corrections for the thermodynamics of uniform truncated systems are possible. In particular, results for the simple point charge/extended (SPC/E) water model treated with spherically truncated Coulomb interactions suggested by local molecular field theory [J. M. Rodgers and J. D. Weeks, Proc. Natl. Acad. Sci. U.S.A. 105, 19136 (2008)] are presented. We extend the results developed by Chandler [J. Chem. Phys. 65, 2925 (1976)] so that we may treat the thermodynamics of mixtures of flexible charged and uncharged molecules simulated with spherical truncations. We show that the energy and pressure of spherically truncated bulk SPC/E water are easily corrected using exact second-moment-like conditions on long-ranged structure. Furthermore, applying the pressure correction as an external pressure removes the density errors observed by other research groups in NPT simulations of spherically truncated bulk species.

Physics and Its Interfaces with Medicinal Chemistry and Drug Design

NASA Astrophysics Data System (ADS)

Santos, Ricardo N.; Andricopulo, Adriano D.

2013-08-01

Medicinal chemistry is a multidisciplinary subject that integrates knowledge from a variety of fields of science, including, but not limited to, chemistry, biology, and physics. The area of drug design involves the cooperative work of scientists with a diverse range of backgrounds and technical skills, trying to tackle complex problems using an integration of approaches and methods. One important contribution to this field comes from physics through studies that attempt to identify and quantify the molecular interactions between small molecules (drugs) and biological targets (receptors), such as the forces that govern the interactions, the thermodynamics of the drug-receptor interactions, and so on. In this context, the interfaces of physics, medicinal chemistry, and drug design are of vital importance for the development of drugs that not only have the right chemistry but also the right intermolecular properties to interact at the macromolecular level, providing useful information about the principles and molecular mechanisms underlying the therapeutic action of drugs. This article highlights some of the most important connections between physics and medicinal chemistry in the design of new drugs.

webPIPSA: a web server for the comparison of protein interaction properties

PubMed Central

Richter, Stefan; Wenzel, Anne; Stein, Matthias; Gabdoulline, Razif R.; Wade, Rebecca C.

2008-01-01

Protein molecular interaction fields are key determinants of protein functionality. PIPSA (Protein Interaction Property Similarity Analysis) is a procedure to compare and analyze protein molecular interaction fields, such as the electrostatic potential. PIPSA may assist in protein functional assignment, classification of proteins, the comparison of binding properties and the estimation of enzyme kinetic parameters. webPIPSA is a web server that enables the use of PIPSA to compare and analyze protein electrostatic potentials. While PIPSA can be run with downloadable software (see http://projects.eml.org/mcm/software/pipsa), webPIPSA extends and simplifies a PIPSA run. This allows non-expert users to perform PIPSA for their protein datasets. With input protein coordinates, the superposition of protein structures, as well as the computation and analysis of electrostatic potentials, is automated. The results are provided as electrostatic similarity matrices from an all-pairwise comparison of the proteins which can be subjected to clustering and visualized as epograms (tree-like diagrams showing electrostatic potential differences) or heat maps. webPIPSA is freely available at: http://pipsa.eml.org. PMID:18420653

Dielectric properties of crystalline organic molecular films in the limit of zero overlap

DOE Office of Scientific and Technical Information (OSTI.GOV)

D’Avino, Gabriele, E-mail: gabriele.davino@gmail.com; Vanzo, Davide; Soos, Zoltán G., E-mail: soos@princeton.edu

2016-01-21

We present the calculation of the static dielectric susceptibility tensor and dipole field sums in thin molecular films in the well-defined limit of zero intermolecular overlap. Microelectrostatic and charge redistribution approaches are applied to study the evolution of dielectric properties from one to a few molecular layers in films of different conjugated molecules with organic electronics applications. Because of the conditional convergence of dipolar interactions, dipole fields depend on the shape of the sample and different values are found in the middle layer of a thick film and in the bulk. The shape dependence is eliminated when depolarization is takenmore » into account, and the dielectric tensor of molecular films converges to the bulk limit within a few molecular layers. We quantify the magnitude of surface effects and interpret general trends among different systems in terms of molecular properties, such as shape, polarizability anisotropy, and supramolecular organization. A connection between atomistic models for molecular dielectrics and simpler theories for polarizable atomic lattices is also provided.« less

Measurement of untruncated nuclear spin interactions via zero- to ultralow-field nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Blanchard, J. W.; Sjolander, T. F.; King, J. P.; Ledbetter, M. P.; Levine, E. H.; Bajaj, V. S.; Budker, D.; Pines, A.

2015-12-01

Zero- to ultralow-field nuclear magnetic resonance (ZULF NMR) provides a new regime for the measurement of nuclear spin-spin interactions free from the effects of large magnetic fields, such as truncation of terms that do not commute with the Zeeman Hamiltonian. One such interaction, the magnetic dipole-dipole coupling, is a valuable source of spatial information in NMR, though many terms are unobservable in high-field NMR, and the coupling averages to zero under isotropic molecular tumbling. Under partial alignment, this information is retained in the form of so-called residual dipolar couplings. We report zero- to ultralow-field NMR measurements of residual dipolar couplings in acetonitrile-2-13C aligned in stretched polyvinyl acetate gels. This permits the investigation of dipolar couplings as a perturbation on the indirect spin-spin J coupling in the absence of an applied magnetic field. As a consequence of working at zero magnetic field, we observe terms of the dipole-dipole coupling Hamiltonian that are invisible in conventional high-field NMR. This technique expands the capabilities of zero- to ultralow-field NMR and has potential applications in precision measurement of subtle physical interactions, chemical analysis, and characterization of local mesoscale structure in materials.

3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors

PubMed Central

Fang, Yajing; Lu, Yulin; Zang, Xixi; Wu, Ting; Qi, XiaoJuan; Pan, Siyi; Xu, Xiaoyun

2016-01-01

Flavonoids are potential antibacterial agents. However, key substituents and mechanism for their antibacterial activity have not been fully investigated. The quantitative structure-activity relationship (QSAR) and molecular docking of flavonoids relating to potent anti-Escherichia coli agents were investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were developed by using the pIC50 values of flavonoids. The cross-validated coefficient (q2) values for CoMFA (0.743) and for CoMSIA (0.708) were achieved, illustrating high predictive capabilities. Selected descriptors for the CoMFA model were ClogP (logarithm of the octanol/water partition coefficient), steric and electrostatic fields, while, ClogP, electrostatic and hydrogen bond donor fields were used for the CoMSIA model. Molecular docking results confirmed that half of the tested flavonoids inhibited DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids changed their orientation, resulting in a decrease of inhibitory activity. Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4-carbonyl groups were found to be crucial active substituents of flavonoids by interacting with key residues of GyrB, which were in agreement with the QSAR study results. These results provide valuable information for structure requirements of flavonoids as antibacterial agents. PMID:27049530

Low-energy excitations of a Bose-Einstein condensate of rigid rotor molecules

NASA Astrophysics Data System (ADS)

Smith, Joseph; Jones, Evan; Rittenhouse, Seth; Wilson, Ryan; Peden, Brandon

2017-04-01

We investigate the properties of the ground state and low-lying excitations of an oblate Bose-Einstein condensate composed of rigid rotor molecules in the presence of an external polarizing electric field. We build in a quantum model of molecular polarizability by including the full manifold of rotational states. The interplay between spatial and microscopic degrees of freedom via feedback between the molecular polarizability and inter-molecular dipole-dipole interactions leads to a rich quasi-particle spectrum. Under large applied fields, we reproduce the well-understood density-wave rotonization that appears in a fully polarized dipolar BEC, but under smaller applied fields, we predict the emergence of a spin wave instability and possible new stable ground state phases. We gratefully acknowledge support from the National Science Foundation under Grant No. PHYS-1516421.

Non-linear non-local molecular electrodynamics with nano-optical fields.

PubMed

Chernyak, Vladimir Y; Saurabh, Prasoon; Mukamel, Shaul

2015-10-28

The interaction of optical fields sculpted on the nano-scale with matter may not be described by the dipole approximation since the fields may vary appreciably across the molecular length scale. Rather than incrementally adding higher multipoles, it is advantageous and more physically transparent to describe the optical process using non-local response functions that intrinsically include all multipoles. We present a semi-classical approach for calculating non-local response functions based on the minimal coupling Hamiltonian. The first, second, and third order response functions are expressed in terms of correlation functions of the charge and the current densities. This approach is based on the gauge invariant current rather than the polarization, and on the vector potential rather than the electric and magnetic fields.

Evaluation of the exchange interaction and crystal fields in a prototype Dy2 SMM

NASA Astrophysics Data System (ADS)

Zhang, Qing; Sarachik, Myriam; Baker, Michael; Chen, Yizhang; Kent, Andrew; Pineda, Eufemio; McInnes, Eric

In order to gain an understanding of the INS and magnetization data obtained for Dy2, the simplest member of a newly synthesized family of dysprosium-based molecular magnets, we report on calculations of the magnetic behavior of a Dy2 cluster with the formula [hqH2][Dy2(hq)4(NO3)3].MeOH. The molecular complex contains one high symmetry Dy(III) ion and one low symmetry Dy(III) ion. Our calculations suggest that exchange coupling between the two ions controls the behavior of the magnetization at low temperature, while the crystal field of the low symmetry Dy(III) ion controls the behavior at higher temperature. A point charge electrostatic model, based on crystallographic coordinates, provides a starting point for the determination of the crystal field. Parameters in these calculations are adjusted to provide best fits to inelastic neutron scattering data (INS) and low temperature magnetometry: the INS measurements access crystal field energies and low temperature magnetization probes the Dy-Dy exchange interaction. Work supported by ARO W911NF-13-1-1025 (CCNY) and NSF-DMR-1309202 (NYU).

Ab initio folding of proteins using all-atom discrete molecular dynamics

PubMed Central

Ding, Feng; Tsao, Douglas; Nie, Huifen; Dokholyan, Nikolay V.

2008-01-01

Summary Discrete molecular dynamics (DMD) is a rapid sampling method used in protein folding and aggregation studies. Until now, DMD was used to perform simulations of simplified protein models in conjunction with structure-based force fields. Here, we develop an all-atom protein model and a transferable force field featuring packing, solvation, and environment-dependent hydrogen bond interactions. Using the replica exchange method, we perform folding simulations of six small proteins (20–60 residues) with distinct native structures. In all cases, native or near-native states are reached in simulations. For three small proteins, multiple folding transitions are observed and the computationally-characterized thermodynamics are in quantitative agreement with experiments. The predictive power of all-atom DMD highlights the importance of environment-dependent hydrogen bond interactions in modeling protein folding. The developed approach can be used for accurate and rapid sampling of conformational spaces of proteins and protein-protein complexes, and applied to protein engineering and design of protein-protein interactions. PMID:18611374

Effect of cholesterol on electrostatics in lipid-protein films of a pulmonary surfactant.

PubMed

Finot, Eric; Leonenko, Yuri; Moores, Brad; Eng, Lukas; Amrein, Matthias; Leonenko, Zoya

2010-02-02

We report the changes in the electrical properties of the lipid-protein film of pulmonary surfactant produced by excess cholesterol. Pulmonary surfactant (PS) is a complex lipid-protein mixture that forms a molecular film at the interface of the lung's epithelia. The defined molecular arrangement of the lipids and proteins of the surfactant film gives rise to the locally highly variable electrical surface potential of the interface, which becomes considerably altered in the presence of cholesterol. With frequency modulation Kelvin probe force microscopy (FM-KPFM) and force measurements, complemented by theoretical analysis, we showed that excess cholesterol significantly changes the electric field around a PS film because of the presence of nanometer-sized electrostatic domains and affects the electrostatic interaction of an AFM probe with a PS film. These changes in the local electrical field would greatly alter the interaction of the surfactant film with charged species and would immediately impact the manner in which inhaled (often charged) airborne nanoparticles and fibers might interact with the lung interface.

Molecular sieving using nanofilters: past, present and future.

PubMed

Han, Jongyoon; Fu, Jianping; Schoch, Reto B

2008-01-01

Filtration of molecules by nanometer-sized structures is ubiquitous in our everyday life, but our understanding of such molecular filtration processes is far less than desired. Until recently, one of the main reasons was the lack of experimental methods that can help provide detailed, microscopic pictures of molecule-nanostructure interactions. Several innovations in experimental methods, such as nuclear track-etched membranes developed in the 70s, and more recent development of nanofluidic molecular filters, played pivotal roles in advancing our understanding. With the ability to make truly molecular-scale filters and pores with well-defined sizes, shapes, and surface properties, now we are well positioned to engineer better functionality in molecular sieving, separation and other membrane applications. Reviewing past theoretical developments (often scattered across different fields) and connecting them to the most recent advances in the field would be essential to get a full, unified view on this important engineering question.

A GPU-accelerated immersive audio-visual framework for interaction with molecular dynamics using consumer depth sensors.

PubMed

Glowacki, David R; O'Connor, Michael; Calabró, Gaetano; Price, James; Tew, Philip; Mitchell, Thomas; Hyde, Joseph; Tew, David P; Coughtrie, David J; McIntosh-Smith, Simon

2014-01-01

With advances in computational power, the rapidly growing role of computational/simulation methodologies in the physical sciences, and the development of new human-computer interaction technologies, the field of interactive molecular dynamics seems destined to expand. In this paper, we describe and benchmark the software algorithms and hardware setup for carrying out interactive molecular dynamics utilizing an array of consumer depth sensors. The system works by interpreting the human form as an energy landscape, and superimposing this landscape on a molecular dynamics simulation to chaperone the motion of the simulated atoms, affecting both graphics and sonified simulation data. GPU acceleration has been key to achieving our target of 60 frames per second (FPS), giving an extremely fluid interactive experience. GPU acceleration has also allowed us to scale the system for use in immersive 360° spaces with an array of up to ten depth sensors, allowing several users to simultaneously chaperone the dynamics. The flexibility of our platform for carrying out molecular dynamics simulations has been considerably enhanced by wrappers that facilitate fast communication with a portable selection of GPU-accelerated molecular force evaluation routines. In this paper, we describe a 360° atmospheric molecular dynamics simulation we have run in a chemistry/physics education context. We also describe initial tests in which users have been able to chaperone the dynamics of 10-alanine peptide embedded in an explicit water solvent. Using this system, both expert and novice users have been able to accelerate peptide rare event dynamics by 3-4 orders of magnitude.

Unraveling Hydrophobic Interactions at the Molecular Scale Using Force Spectroscopy and Molecular Dynamics Simulations.

PubMed

Stock, Philipp; Monroe, Jacob I; Utzig, Thomas; Smith, David J; Shell, M Scott; Valtiner, Markus

2017-03-28

Interactions between hydrophobic moieties steer ubiquitous processes in aqueous media, including the self-organization of biologic matter. Recent decades have seen tremendous progress in understanding these for macroscopic hydrophobic interfaces. Yet, it is still a challenge to experimentally measure hydrophobic interactions (HIs) at the single-molecule scale and thus to compare with theory. Here, we present a combined experimental-simulation approach to directly measure and quantify the sequence dependence and additivity of HIs in peptide systems at the single-molecule scale. We combine dynamic single-molecule force spectroscopy on model peptides with fully atomistic, both equilibrium and nonequilibrium, molecular dynamics (MD) simulations of the same systems. Specifically, we mutate a flexible (GS) 5 peptide scaffold with increasing numbers of hydrophobic leucine monomers and measure the peptides' desorption from hydrophobic self-assembled monolayer surfaces. Based on the analysis of nonequilibrium work-trajectories, we measure an interaction free energy that scales linearly with 3.0-3.4 k B T per leucine. In good agreement, simulations indicate a similar trend with 2.1 k B T per leucine, while also providing a detailed molecular view into HIs. This approach potentially provides a roadmap for directly extracting qualitative and quantitative single-molecule interactions at solid/liquid interfaces in a wide range of fields, including interactions at biointerfaces and adhesive interactions in industrial applications.

Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device.

PubMed

Ndesendo, Valence M K; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Buchmann, Eckhart; Meyer, Leith C R; Khan, Riaz A

2012-01-01

This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= -46.33 kcalmol(-1)). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm(2)). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina.

Challenging AQP4 druggability for NMO-IgG antibody binding using molecular dynamics and molecular interaction fields.

PubMed

Mangiatordi, Giuseppe Felice; Alberga, Domenico; Siragusa, Lydia; Goracci, Laura; Lattanzi, Gianluca; Nicolotti, Orazio

2015-07-01

Neuromyelitis optica (NMO) is a multiple sclerosis-like immunopathology disease affecting optic nerves and the spinal cord. Its pathological hallmark is the deposition of a typical immunoglobulin, called NMO-IgG, against the water channel Aquaporin-4 (AQP4). Preventing NMO-IgG binding would represent a valuable molecular strategy for a focused NMO therapy. The recent observation that aspartate in position 69 (D69) is determinant for the formation of NMO-IgG epitopes prompted us to carry out intensive Molecular Dynamics (MD) studies on a number of single-point AQP4 mutants. Here, we report a domino effect originating from the point mutation at position 69: we find that the side chain of T62 is reoriented far from its expected position leaning on the lumen of the pore. More importantly, the strength of the H-bond interaction between L53 and T56, at the basis of the loop A, is substantially weakened. These events represent important pieces of a clear-cut mechanistic rationale behind the failure of the NMO-IgG binding, while the water channel function as well as the propensity to aggregate into OAPs remains unaltered. The molecular interaction fields (MIF)-based analysis of cavities complemented MD findings indicating a putative binding site comprising the same residues determining epitope reorganization. In this respect, docking studies unveiled an intriguing perspective to address the future design of small drug-like compounds against NMO. In agreement with recent experimental observations, the present study is the first computational attempt to elucidate NMO-IgG binding at the molecular level, as well as a first effort toward a less elusive AQP4 druggability. Copyright © 2015 Elsevier B.V. All rights reserved.

Gauge-invariant expectation values of the energy of a molecule in an electromagnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandal, Anirban; Hunt, Katharine L. C.

In this paper, we show that the full Hamiltonian for a molecule in an electromagnetic field can be separated into a molecular Hamiltonian and a field Hamiltonian, both with gauge-invariant expectation values. The expectation value of the molecular Hamiltonian gives physically meaningful results for the energy of a molecule in a time-dependent applied field. In contrast, the usual partitioning of the full Hamiltonian into molecular and field terms introduces an arbitrary gauge-dependent potential into the molecular Hamiltonian and leaves a gauge-dependent form of the Hamiltonian for the field. With the usual partitioning of the Hamiltonian, this same problem of gaugemore » dependence arises even in the absence of an applied field, as we show explicitly by considering a gauge transformation from zero applied field and zero external potentials to zero applied field, but non-zero external vector and scalar potentials. We resolve this problem and also remove the gauge dependence from the Hamiltonian for a molecule in a non-zero applied field and from the field Hamiltonian, by repartitioning the full Hamiltonian. It is possible to remove the gauge dependence because the interaction of the molecular charges with the gauge potential cancels identically with a gauge-dependent term in the usual form of the field Hamiltonian. We treat the electromagnetic field classically and treat the molecule quantum mechanically, but nonrelativistically. Our derivation starts from the Lagrangian for a set of charged particles and an electromagnetic field, with the particle coordinates, the vector potential, the scalar potential, and their time derivatives treated as the variables in the Lagrangian. We construct the full Hamiltonian using a Lagrange multiplier method originally suggested by Dirac, partition this Hamiltonian into a molecular term H{sub m} and a field term H{sub f}, and show that both H{sub m} and H{sub f} have gauge-independent expectation values. Any gauge may be chosen for the calculations; but following our partitioning, the expectation values of the molecular Hamiltonian are identical to those obtained directly in the Coulomb gauge. As a corollary of this result, the power absorbed by a molecule from a time-dependent, applied electromagnetic field is equal to the time derivative of the non-adiabatic term in the molecular energy, in any gauge.« less

Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

DOE PAGES

Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; ...

2015-06-04

Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstratemore » prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.« less

Machine Learning Predictions of Molecular Properties: Accurate Many-Body Potentials and Nonlocality in Chemical Space

PubMed Central

2015-01-01

Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. In addition, the same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies. PMID:26113956

Molecular design of new aggrecanases-2 inhibitors.

PubMed

Shan, Zhi Jie; Zhai, Hong Lin; Huang, Xiao Yan; Li, Li Na; Zhang, Xiao Yun

2013-10-01

Aggrecanases-2 is a very important potential drug target for the treatment of osteoarthritis. In this study, a series of known aggrecanases-2 inhibitors was analyzed by the technologies of three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking. Two 3D-QSAR models, which based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods, were established. Molecular docking was employed to explore the details of the interaction between inhibitors and aggrecanases-2 protein. According to the analyses for these models, several new potential inhibitors with higher activity predicted were designed, and were supported by the simulation of molecular docking. This work propose the fast and effective approach to design and prediction for new potential inhibitors, and the study of the interaction mechanism provide a better understanding for the inhibitors binding into the target protein, which will be useful for the structure-based drug design and modifications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Controlling single-molecule junction conductance by molecular interactions

NASA Astrophysics Data System (ADS)

Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

2015-07-01

For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment.

Molecular Mediators Governing Iron-Copper Interactions

PubMed Central

Gulec, Sukru; Collins, James F.

2015-01-01

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states. PMID:24995690

Molecular Interaction Control in Diblock Copolymer Blends and Multiblock Copolymers with Opposite Phase Behaviors

NASA Astrophysics Data System (ADS)

Cho, Junhan

2014-03-01

Here we show how to control molecular interactions via mixing AB and AC diblock copolymers, where one copolymer exhibits upper order-disorder transition and the other does lower disorder-order transition. Linear ABC triblock copolymers possessing both barotropic and baroplastic pairs are also taken into account. A recently developed random-phase approximation (RPA) theory and the self-consistent field theory (SCFT) for general compressible mixtures are used to analyze stability criteria and morphologies for the given systems. It is demonstrated that the copolymer systems can yield a variety of phase behaviors in their temperature and pressure dependence upon proper mixing conditions and compositions, which is caused by the delicate force fields generated in the systems. We acknowledge the financial support from National Research Foundation of Korea and Center for Photofunctional Energy Materials.

ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology

PubMed Central

2015-01-01

Background Sufficient knowledge of molecular and genetic interactions, which comprise the entire basis of the functioning of living systems, is one of the necessary requirements for successfully answering almost any research question in the field of biology and medicine. To date, more than 24 million scientific papers can be found in PubMed, with many of them containing descriptions of a wide range of biological processes. The analysis of such tremendous amounts of data requires the use of automated text-mining approaches. Although a handful of tools have recently been developed to meet this need, none of them provide error-free extraction of highly detailed information. Results The ANDSystem package was developed for the reconstruction and analysis of molecular genetic networks based on an automated text-mining technique. It provides a detailed description of the various types of interactions between genes, proteins, microRNA's, metabolites, cellular components, pathways and diseases, taking into account the specificity of cell lines and organisms. Although the accuracy of ANDSystem is comparable to other well known text-mining tools, such as Pathway Studio and STRING, it outperforms them in having the ability to identify an increased number of interaction types. Conclusion The use of ANDSystem, in combination with Pathway Studio and STRING, can improve the quality of the automated reconstruction of molecular and genetic networks. ANDSystem should provide a useful tool for researchers working in a number of different fields, including biology, biotechnology, pharmacology and medicine. PMID:25881313

The interactions of ants with their biotic environment.

PubMed

Chomicki, Guillaume; Renner, Susanne S

2017-03-15

This s pecial feature results from the symposium 'Ants 2016: ant interactions with their biotic environments' held in Munich in May 2016 and deals with the interactions between ants and other insects, plants, microbes and fungi, studied at micro- and macroevolutionary levels with a wide range of approaches, from field ecology to next-generation sequencing, chemical ecology and molecular genetics. In this paper, we review key aspects of these biotic interactions to provide background information for the papers of this s pecial feature After listing the major types of biotic interactions that ants engage in, we present a brief overview of ant/ant communication, ant/plant interactions, ant/fungus symbioses, and recent insights about ants and their endosymbionts. Using a large molecular clock-dated Formicidae phylogeny, we map the evolutionary origins of different ant clades' interactions with plants, fungi and hemiptera. Ants' biotic interactions provide ideal systems to address fundamental ecological and evolutionary questions about mutualism, coevolution, adaptation and animal communication. © 2017 The Author(s).

The interactions of ants with their biotic environment

PubMed Central

Renner, Susanne S.

2017-01-01

This special feature results from the symposium ‘Ants 2016: ant interactions with their biotic environments’ held in Munich in May 2016 and deals with the interactions between ants and other insects, plants, microbes and fungi, studied at micro- and macroevolutionary levels with a wide range of approaches, from field ecology to next-generation sequencing, chemical ecology and molecular genetics. In this paper, we review key aspects of these biotic interactions to provide background information for the papers of this special feature. After listing the major types of biotic interactions that ants engage in, we present a brief overview of ant/ant communication, ant/plant interactions, ant/fungus symbioses, and recent insights about ants and their endosymbionts. Using a large molecular clock-dated Formicidae phylogeny, we map the evolutionary origins of different ant clades' interactions with plants, fungi and hemiptera. Ants' biotic interactions provide ideal systems to address fundamental ecological and evolutionary questions about mutualism, coevolution, adaptation and animal communication. PMID:28298352

The Halogen Bond

PubMed Central

2016-01-01

The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design. PMID:26812185

Plasmonic nanoparticles for bioanalytics and therapy at the limit

NASA Astrophysics Data System (ADS)

Schneider, T.; Wirth, J.; Garwe, F.; Csáki, A.; Fritzsche, W.

2011-12-01

Noble metal nanoparticles interacting with electromagnetic waves exhibit the effect of localized surface plasmon resonance (LSPR) based on the collective oscillation of their conduction electrons. Local refractive index changes by a (bio) molecular layer surrounding the nanoparticle are important for a variety of research areas like optics and life sciences. In this work we demonstrate the potential of two applications in the field of molecular plasmonics, single nanoparticle sensors and nanoantennas, situated between plasmonics effects and the molecular world.

Density-Functional Theory with Dispersion-Correcting Potentials for Methane: Bridging the Efficiency and Accuracy Gap between High-Level Wave Function and Classical Molecular Mechanics Methods.

PubMed

Torres, Edmanuel; DiLabio, Gino A

2013-08-13

Large clusters of noncovalently bonded molecules can only be efficiently modeled by classical mechanics simulations. One prominent challenge associated with this approach is obtaining force-field parameters that accurately describe noncovalent interactions. High-level correlated wave function methods, such as CCSD(T), are capable of correctly predicting noncovalent interactions, and are widely used to produce reference data. However, high-level correlated methods are generally too computationally costly to generate the critical reference data required for good force-field parameter development. In this work we present an approach to generate Lennard-Jones force-field parameters to accurately account for noncovalent interactions. We propose the use of a computational step that is intermediate to CCSD(T) and classical molecular mechanics, that can bridge the accuracy and computational efficiency gap between them, and demonstrate the efficacy of our approach with methane clusters. On the basis of CCSD(T)-level binding energy data for a small set of methane clusters, we develop methane-specific, atom-centered, dispersion-correcting potentials (DCPs) for use with the PBE0 density-functional and 6-31+G(d,p) basis sets. We then use the PBE0-DCP approach to compute a detailed map of the interaction forces associated with the removal of a single methane molecule from a cluster of eight methane molecules and use this map to optimize the Lennard-Jones parameters for methane. The quality of the binding energies obtained by the Lennard-Jones parameters we obtained is assessed on a set of methane clusters containing from 2 to 40 molecules. Our Lennard-Jones parameters, used in combination with the intramolecular parameters of the CHARMM force field, are found to closely reproduce the results of our dispersion-corrected density-functional calculations. The approach outlined can be used to develop Lennard-Jones parameters for any kind of molecular system.

Facile and controllable one-step fabrication of molecularly imprinted polymer membrane by magnetic field directed self-assembly for electrochemical sensing of glutathione.

PubMed

Zhu, Wanying; Jiang, Guoyi; Xu, Lei; Li, Bingzhi; Cai, Qizhi; Jiang, Huijun; Zhou, Xuemin

2015-07-30

Based on magnetic field directed self-assembly (MDSA) of the ternary Fe3O4@PANI/rGO nanocomposites, a facile and controllable molecularly imprinted electrochemical sensor (MIES) was fabricated through a one-step approach for detection of glutathione (GSH). The ternary Fe3O4@PANI/rGO nanocomposites were obtained by chemical oxidative polymerization and intercalation of Fe3O4@PANI into the graphene oxide layers via π-π stacking interaction, followed by reduction of graphene oxide in the presence of hydrazine hydrate. In molecular imprinting process, the pre-polymers, including GSH as template molecule, Fe3O4@PANI/rGO nanocomposites as functional monomers and pyrrole as both cross-linker and co-monomer, was assembled through N-H hydrogen bonds and the electrostatic interaction, and then was rapidly oriented onto the surface of MGCE under the magnetic field induction. Subsequently, the electrochemical GSH sensor was formed by electropolymerization. In this work, the ternary Fe3O4@PANI/rGO nanocomposites could not only provide available functionalized sites in the matrix to form hydrogen bond and electrostatic interaction with GSH, but also afford a promoting network for electron transfer. Moreover, the biomimetic sensing membrane could be controlled more conveniently and effectively by adjusting the magnetic field strength. The as-prepared controllable sensor showed good stability and reproducibility for the determination of GSH with the detection limit reaching 3 nmol L(-1) (S/N = 3). In addition, the highly sensitive and selective biomimetic sensor has been successfully used for the clinical determination of GSH in biological samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Level crossings and zero-field splitting in the {Cr8}-cubane spin cluster studied using inelastic neutron scattering and magnetization

NASA Astrophysics Data System (ADS)

Vaknin, D.; Garlea, V. O.; Demmel, F.; Mamontov, E.; Nojiri, H.; Martin, C.; Chiorescu, I.; Qiu, Y.; Kögerler, P.; Fielden, J.; Engelhardt, L.; Rainey, C.; Luban, M.

2010-11-01

Inelastic neutron scattering (INS) in variable magnetic field and high-field magnetization measurements in the millikelvin temperature range were performed to gain insight into the low-energy magnetic excitation spectrum and the field-induced level crossings in the molecular spin cluster {Cr8}-cubane. These complementary techniques provide consistent estimates of the lowest level-crossing field. The overall features of the experimental data are explained using an isotropic Heisenberg model, based on three distinct exchange interactions linking the eight CrIII paramagnetic centers (spins s = 3/2), that is supplemented with a relatively large molecular magnetic anisotropy term for the lowest S = 1 multiplet. It is noted that the existence of the anisotropy is clearly evident from the magnetic field dependence of the excitations in the INS measurements, while the magnetization measurements are not sensitive to its effects.

Level crossings and zero-field splitting in the {Cr8}-cubane spin-cluster studied using inelastic neutron scattering and magnetization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaknin, D.; Garlea, Vasile O; Demmel, F.

Inelastic neutron scattering (INS) in variable magnetic field and high-field magnetization measurements in the millikelvin temperature range were performed to gain insight into the low-energy magnetic excitation spectrum and the field-induced level crossings in the molecular spin cluster {Cr8}-cubane. These complementary techniques provide consistent estimates of the lowest level-crossing field. The overall features of the experimental data are explained using an isotropic Heisenberg model, based on three distinct exchange interactions linking the eight CrIII paramagnetic centers (spins s = 3/2), that is supplemented with a relatively large molecular magnetic anisotropy term for the lowest S = 1 multiplet. It ismore » noted that the existence of the anisotropy is clearly evident from the magnetic field dependence of the excitations in the INS measurements, while the magnetization measurements are not sensitive to its effects.« less

Parallel mapping of optical near-field interactions by molecular motor-driven quantum dots.

PubMed

Groß, Heiko; Heil, Hannah S; Ehrig, Jens; Schwarz, Friedrich W; Hecht, Bert; Diez, Stefan

2018-04-30

In the vicinity of metallic nanostructures, absorption and emission rates of optical emitters can be modulated by several orders of magnitude 1,2 . Control of such near-field light-matter interaction is essential for applications in biosensing 3 , light harvesting 4 and quantum communication 5,6 and requires precise mapping of optical near-field interactions, for which single-emitter probes are promising candidates 7-11 . However, currently available techniques are limited in terms of throughput, resolution and/or non-invasiveness. Here, we present an approach for the parallel mapping of optical near-field interactions with a resolution of <5 nm using surface-bound motor proteins to transport microtubules carrying single emitters (quantum dots). The deterministic motion of the quantum dots allows for the interpolation of their tracked positions, resulting in an increased spatial resolution and a suppression of localization artefacts. We apply this method to map the near-field distribution of nanoslits engraved into gold layers and find an excellent agreement with finite-difference time-domain simulations. Our technique can be readily applied to a variety of surfaces for scalable, nanometre-resolved and artefact-free near-field mapping using conventional wide-field microscopes.

Solvation of fluoro-acetonitrile in water by 2D-IR spectroscopy: A combined experimental-computational study

NASA Astrophysics Data System (ADS)

Cazade, Pierre-André; Tran, Halina; Bereau, Tristan; Das, Akshaya K.; Kläsi, Felix; Hamm, Peter; Meuwly, Markus

2015-06-01

The solvent dynamics around fluorinated acetonitrile is characterized by 2-dimensional infrared spectroscopy and atomistic simulations. The lineshape of the linear infrared spectrum is better captured by semiempirical (density functional tight binding) mixed quantum mechanical/molecular mechanics simulations, whereas force field simulations with multipolar interactions yield lineshapes that are significantly too narrow. For the solvent dynamics, a relatively slow time scale of 2 ps is found from the experiments and supported by the mixed quantum mechanical/molecular mechanics simulations. With multipolar force fields fitted to the available thermodynamical data, the time scale is considerably faster—on the 0.5 ps time scale. The simulations provide evidence for a well established CF-HOH hydrogen bond (population of 25%) which is found from the radial distribution function g(r) from both, force field and quantum mechanics/molecular mechanics simulations.

Quantum mechanical force fields for condensed phase molecular simulations

NASA Astrophysics Data System (ADS)

Giese, Timothy J.; York, Darrin M.

2017-09-01

Molecular simulations are powerful tools for providing atomic-level details into complex chemical and physical processes that occur in the condensed phase. For strongly interacting systems where quantum many-body effects are known to play an important role, density-functional methods are often used to provide the model with the potential energy used to drive dynamics. These methods, however, suffer from two major drawbacks. First, they are often too computationally intensive to practically apply to large systems over long time scales, limiting their scope of application. Second, there remain challenges for these models to obtain the necessary level of accuracy for weak non-bonded interactions to obtain quantitative accuracy for a wide range of condensed phase properties. Quantum mechanical force fields (QMFFs) provide a potential solution to both of these limitations. In this review, we address recent advances in the development of QMFFs for condensed phase simulations. In particular, we examine the development of QMFF models using both approximate and ab initio density-functional models, the treatment of short-ranged non-bonded and long-ranged electrostatic interactions, and stability issues in molecular dynamics calculations. Example calculations are provided for crystalline systems, liquid water, and ionic liquids. We conclude with a perspective for emerging challenges and future research directions.

Testing the Two-Layer Model for Correcting Clear Sky Reflectance near Clouds

NASA Technical Reports Server (NTRS)

Wen, Guoyong; Marshak, Alexander; Evans, Frank; Varnai, Tamas; Levy, Rob

2015-01-01

A two-layer model (2LM) was developed in our earlier studies to estimate the clear sky reflectance enhancement due to cloud-molecular radiative interaction at MODIS at 0.47 micrometers. Recently, we extended the model to include cloud-surface and cloud-aerosol radiative interactions. We use the LES/SHDOM simulated 3D true radiation fields to test the 2LM for reflectance enhancement at 0.47 micrometers. We find: The simple model captures the viewing angle dependence of the reflectance enhancement near cloud, suggesting the physics of this model is correct; the cloud-molecular interaction alone accounts for 70 percent of the enhancement; the cloud-surface interaction accounts for 16 percent of the enhancement; the cloud-aerosol interaction accounts for an additional 13 percent of the enhancement. We conclude that the 2LM is simple to apply and unbiased.

Van der Waals Interactions of Organic Molecules on Semiconductor and Metal Surfaces: a Comparative Study

NASA Astrophysics Data System (ADS)

Li, Guo; Cooper, Valentino; Cho, Jun-Hyung; Tamblyn, Isaac; Du, Shixuan; Neaton, Jeffrey; Gao, Hong-Jun; Zhang, Zhenyu

2012-02-01

We present a comparative investigation of vdW interactions of the organic molecules on semiconductor and metal surfaces using the DFT method implemented with vdW-DF. For styrene/H-Si(100), the vdW interactions reverse the effective intermolecular interaction from repulsive to attractive, ensuring preferred growth of long wires as observed experimentally. We further propose that an external E field and the selective creation of Si dangling bonds can drastically improve the ordered arrangement of the molecular nanowires [1]. For BDA/Au(111), the vdW interactions not only dramatically enhances the adsorption energies, but also significantly changes the molecular configurations. In the azobenzene/Ag(111) system, vdW-DF produces superior predictions for the adsorption energy than those obtained with other vdW corrected DFT approaches, providing evidence for the applicability of the vdW-DF method [2].

Seeing with the nano-eye: accessing structure, function, and dynamics of matter on its natural length and time scales

NASA Astrophysics Data System (ADS)

Raschke, Markus

2015-03-01

To understand and ultimately control the properties of most functional materials, from molecular soft-matter to quantum materials, requires access to the structure, coupling, and dynamics on the elementary time and length scales that define the microscopic interactions in these materials. To gain the desired nanometer spatial resolution with simultaneous spectroscopic specificity we combine scanning probe microscopy with different optical, including coherent, nonlinear, and ultrafast spectroscopies. The underlying near-field interaction mediated by the atomic-force or scanning tunneling microscope tip provides the desired deep-sub wavelength nano-focusing enabling few-nm spatial resolution. I will introduce our generalization of the approach in terms of the near-field impedance matching to a quantum system based on special optical antenna-tip designs. The resulting enhanced and qualitatively new forms of light-matter interaction enable measurements of quantum dynamics in an interacting environment or to image the electromagnetic local density of states of thermal radiation. Other applications include the inter-molecular coupling and dynamics in soft-matter hetero-structures, surface plasmon interferometry as a probe of electronic structure and dynamics in graphene, and quantum phase transitions in correlated electron materials. These examples highlight the general applicability of the new near-field microscopy approach, complementing emergent X-ray and electron imaging tools, aiming towards the ultimate goal of probing matter on its most elementary spatio-temporal level.

Systematic Validation of Protein Force Fields against Experimental Data

PubMed Central

Eastwood, Michael P.; Dror, Ron O.; Shaw, David E.

2012-01-01

Molecular dynamics simulations provide a vehicle for capturing the structures, motions, and interactions of biological macromolecules in full atomic detail. The accuracy of such simulations, however, is critically dependent on the force field—the mathematical model used to approximate the atomic-level forces acting on the simulated molecular system. Here we present a systematic and extensive evaluation of eight different protein force fields based on comparisons of experimental data with molecular dynamics simulations that reach a previously inaccessible timescale. First, through extensive comparisons with experimental NMR data, we examined the force fields' abilities to describe the structure and fluctuations of folded proteins. Second, we quantified potential biases towards different secondary structure types by comparing experimental and simulation data for small peptides that preferentially populate either helical or sheet-like structures. Third, we tested the force fields' abilities to fold two small proteins—one α-helical, the other with β-sheet structure. The results suggest that force fields have improved over time, and that the most recent versions, while not perfect, provide an accurate description of many structural and dynamical properties of proteins. PMID:22384157

Molecular modeling of interactions in electronic nose sensors for environmental monitoring

NASA Technical Reports Server (NTRS)

Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Yen, S. -P. S.; Zhou, H.; Manatt, K.

2002-01-01

We report a study aimed at understanding analyte interactions with sensors made from polymer-carbon black composite films. The sensors are used in an Electronic Nose (ENose) which is used for monitoring the breathing air quality in human habitats. The model mimics the experimental conditions of the composite film deposition and formation and was developed using molecular modeling and simulation tools. The Dreiding 2.21 Force Field was used for the polymer and analyte molecules while graphite parameters were assigned to the carbon black atoms. The polymer considered for this work is methyl vinyl ether / maleic acid copolymer. The target analytes include both inorganic (NH3) and organic (methanol) types of compound. Results indicate different composite-analyte interaction behavior.

Insight into the interaction mechanism of human SGLT2 with its inhibitors: 3D-QSAR studies, homology modeling, and molecular docking and molecular dynamics simulations.

PubMed

Dong, Lili; Feng, Ruirui; Bi, Jiawei; Shen, Shengqiang; Lu, Huizhe; Zhang, Jianjun

2018-03-06

Human sodium-dependent glucose co-transporter 2 (hSGLT2) is a crucial therapeutic target in the treatment of type 2 diabetes. In this study, both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to generate three-dimensional quantitative structure-activity relationship (3D-QSAR) models. In the most accurate CoMFA-based and CoMSIA-based QSAR models, the cross-validated coefficients (r 2 cv ) were 0.646 and 0.577, respectively, while the non-cross-validated coefficients (r 2 ) were 0.997 and 0.991, respectively, indicating that both models were reliable. In addition, we constructed a homology model of hSGLT2 in the absence of a crystal structure. Molecular docking was performed to explore the bonding mode of inhibitors to the active site of hSGLT2. Molecular dynamics (MD) simulations and binding free energy calculations using MM-PBSA and MM-GBSA were carried out to further elucidate the interaction mechanism. With regards to binding affinity, we found that hydrogen-bond interactions of Asn51 and Glu75, located in the active site of hSGLT2, with compound 40 were critical. Hydrophobic and electrostatic interactions were shown to enhance activity, in agreement with the results obtained from docking and 3D-QSAR analysis. Our study results shed light on the interaction mode between inhibitors and hSGLT2 and may aid in the development of C-aryl glucoside SGLT2 inhibitors.

The Tai Chi in Star Formation

NASA Astrophysics Data System (ADS)

Li, Hua-bai

2017-10-01

Tai Chi, a Chinese martial art developed based on the laws of nature, emphasises how 'to conquer the unyielding with the yielding'. The recent observation of star formation shows that stars result from the interaction between gravity, turbulence and magnetic fields. This interaction again follows the nature rules that inspired Tai Chi. For example, if self-gravity is the force that dominates, the molecular cloud will collapse isotropically, which compresses magnetic field lines. The density of the yielding field lines increases until magnetic pressure reaches the critical value to support the cloud against the gravitational force in directions perpendicular to the field lines (Lorentz force). Then gravity gives way to Lorentz force, accumulating gas only along the field lines till the gas density achieves the critical value to again compress the field lines. The Tai Chi goes on in a self-similar way.

Molecular Dynamics of β-Hairpin Models of Epigenetic Recognition Motifs

PubMed Central

Zheng, Xiange; Wu, Chuanjie; Ponder, Jay W.; Marshall, Garland R.

2012-01-01

The conformations and stabilities of the β-hairpin model peptides of Waters1,2 have been experimentally characterized as a function of lysine ε-methylation. These models were developed to explore molecular recognition of known epigenetic recognition motifs. This system offered an opportunity to computationally examine the role of cation-π interactions, desolvation of the ε-methylated ammonium groups, and aromatic/aromatic interactions on the observed differences in NMR spectra. AMOEBA, a second-generation force field4, was chosen as it includes both multipole electrostatics and polarizability thought to be essential to accurately characterize such interactions. Independent parameterization of ε-methylated amines was required from which aqueous solvation free energies were estimated and shown to agree with literature values. Molecular dynamics simulations (100 ns) using the derived parameters with model peptides, such as Ac-R-W-V-W-V-N-G-Orn-K(Me)n -I-L-Q-NH2, where n = 0, 1, 2, or 3, were conducted in explicit solvent. Distances between the centers of the indole rings of the two-tryptophan residues, 2 and 4, and the ε-methylated ammonium group on Lys-9 as well as the distance between the N- and C-termini were monitored to estimate the strength and orientation of the cation-π and aromatic/aromatic interactions. In agreement with the experimental data, the stability of the β-hairpin increased significantly with lysine ε-methylation. The ability of MD simulations to reproduce the observed NOEs for the four peptides was further estimated for the monopole-based force fields, AMBER, CHARMM, and OPLSAA. AMOEBA correctly predicted over 80% of the observed NOEs for all four peptides, while the three-monopole force fields were 40–50% predictive in only two cases and approximately 10% in the other ten examples. Preliminary analysis suggests that the decreased cost of desolvation of the substituted ammonium group significantly compensated for the reduced cation-π interaction resulting from the increased separation due to steric bulk of the ε-methylated amines. PMID:22934656

Chemical Evolution of Protostellar Matter

NASA Technical Reports Server (NTRS)

Langer, William D.; vanDishoeck, Ewine F.; Bergin, Edwin A.; Blake, Geoffrey A.; Tielens, Alexander G. G. M.; Velusamy, Thangasamy; Whittet, Douglas C. B.

2000-01-01

We review the chemical processes that are important in the evolution from a molecular cloud core to a protostellar disk. These cover both gas phase and gas grain interactions. The current observational and theoretical state of this field are discussed.

Interaction of toluene with two-color asymmetric laser fields: Controlling the directional emission of molecular hydrogen fragments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaziannis, S.; Kotsina, N.; Kosmidis, C.

The interaction of toluene with strong asymmetric two-color laser irradiation of 40 fs duration is studied by means of Time of flight mass spectrometry. Highly energetic H{sub 2}{sup +} and H{sub 3}{sup +} fragment ions are produced through an isomerization process taking place within transient multiply charged parent ions. Comparative study of deuterium labeled toluene isotopes enables the discrimination between molecular hydrogen fragments formed exclusively within the CH{sub 3}- part from those that require hydrogen atom exchange between the former and the phenyl moiety. It is demonstrated that by manipulating the relative phase of the ω/2ω field components the selectivemore » ionization of oriented toluene molecules can be used as a tool to control the directional emission of the H{sub 2}{sup +}, H{sub 3}{sup +} species.« less

Molecular dynamics simulations of the surface tension and structure of salt solutions and clusters.

PubMed

Sun, Lu; Li, Xin; Hede, Thomas; Tu, Yaoquan; Leck, Caroline; Ågren, Hans

2012-03-15

Sodium halides, which are abundant in sea salt aerosols, affect the optical properties of aerosols and are active in heterogeneous reactions that cause ozone depletion and acid rain problems. Interfacial properties, including surface tension and halide anion distributions, are crucial issues in the study of the aerosols. We present results from molecular dynamics simulations of water solutions and clusters containing sodium halides with the interatomic interactions described by a conventional force field. The simulations reproduce experimental observations that sodium halides increase the surface tension with respect to pure water and that iodide anions reach the outermost layer of water clusters or solutions. It is found that the van der Waals interactions have an impact on the distribution of the halide anions and that a conventional force field with optimized parameters can model the surface tension of the salt solutions with reasonable accuracy. © 2012 American Chemical Society

Molecular modeling of polymer composite interactions with analytes in electronic nose sensors for environmental monitoring in International Space Station

NASA Technical Reports Server (NTRS)

Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Zhou, H.; Manatt, K.

2002-01-01

We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL Electronic Nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings (with no hydrogens). The Dreiding 2.21 force field is used for the polymer and solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4- vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic (ammonia) and organic (methanol, toluene, hydrazine) compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites.

Molecular modeling of polymer composite-analyte interactions in electronic nose sensors

NASA Technical Reports Server (NTRS)

Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Zhou, H.; Manatt, K. S.

2003-01-01

We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL electronic nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereoisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings with no hydrogens. The Dreiding 2.21 force field is used for the polymer, solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4-vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic and organic compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites. c2003 Elsevier Science B.V. All rights reserved.

Electromelting of confined monolayer ice.

PubMed

Qiu, Hu; Guo, Wanlin

2013-05-10

In sharp contrast to the prevailing view that electric fields promote water freezing, here we show by molecular dynamics simulations that monolayer ice confined between two parallel plates can melt into liquid water under a perpendicularly applied electric field. The melting temperature of the monolayer ice decreases with the increasing strength of the external field due to the field-induced disruption of the water-wall interaction induced well-ordered network of the hydrogen bond. This electromelting process should add an important new ingredient to the physics of water.

Mapping the Protein Fold Universe Using the CamTube Force Field in Molecular Dynamics Simulations.

PubMed

Kukic, Predrag; Kannan, Arvind; Dijkstra, Maurits J J; Abeln, Sanne; Camilloni, Carlo; Vendruscolo, Michele

2015-10-01

It has been recently shown that the coarse-graining of the structures of polypeptide chains as self-avoiding tubes can provide an effective representation of the conformational space of proteins. In order to fully exploit the opportunities offered by such a 'tube model' approach, we present here a strategy to combine it with molecular dynamics simulations. This strategy is based on the incorporation of the 'CamTube' force field into the Gromacs molecular dynamics package. By considering the case of a 60-residue polyvaline chain, we show that CamTube molecular dynamics simulations can comprehensively explore the conformational space of proteins. We obtain this result by a 20 μs metadynamics simulation of the polyvaline chain that recapitulates the currently known protein fold universe. We further show that, if residue-specific interaction potentials are added to the CamTube force field, it is possible to fold a protein into a topology close to that of its native state. These results illustrate how the CamTube force field can be used to explore efficiently the universe of protein folds with good accuracy and very limited computational cost.

Mapping the Protein Fold Universe Using the CamTube Force Field in Molecular Dynamics Simulations

PubMed Central

Dijkstra, Maurits J. J.; Abeln, Sanne; Camilloni, Carlo; Vendruscolo, Michele

2015-01-01

It has been recently shown that the coarse-graining of the structures of polypeptide chains as self-avoiding tubes can provide an effective representation of the conformational space of proteins. In order to fully exploit the opportunities offered by such a ‘tube model’ approach, we present here a strategy to combine it with molecular dynamics simulations. This strategy is based on the incorporation of the ‘CamTube’ force field into the Gromacs molecular dynamics package. By considering the case of a 60-residue polyvaline chain, we show that CamTube molecular dynamics simulations can comprehensively explore the conformational space of proteins. We obtain this result by a 20 μs metadynamics simulation of the polyvaline chain that recapitulates the currently known protein fold universe. We further show that, if residue-specific interaction potentials are added to the CamTube force field, it is possible to fold a protein into a topology close to that of its native state. These results illustrate how the CamTube force field can be used to explore efficiently the universe of protein folds with good accuracy and very limited computational cost. PMID:26505754

Study of structural and conformational change in cytochrome, C through molecular dynamic simulation in presence of gold nanoparticles

NASA Astrophysics Data System (ADS)

Moudgil, Lovika; Singh, Baljinder; Kaura, Aman; Singh, Gurinder; Tripathi, S. K.; Saini, G. S. S.

2017-05-01

Proteins are the most abundant organic molecules in living system having diverse structures and various functions than the other classes of macromolecules. We have done Molecular Dynamics (MD) simulation of the Cytochrome,C (Cyt,c) protein found in plants, animals and many unicellular animals in the presence of gold nanoparticles (Au NPs). MD results helped to recognize the amino acids that play important role to make the interaction possible between protein and gold surface. In the present study we have examined the structural change of protein in the presence of gold surface and its adsorption on the surface through MD simulations with the help of Gold-Protein (GolP) force field. Results were further analyzed to understand the protein interaction up to molecular level.

Advanced understanding on electronic structure of molecular semiconductors and their interfaces

NASA Astrophysics Data System (ADS)

Akaike, Kouki

2018-03-01

Understanding the electronic structure of organic semiconductors and their interfaces is critical to optimizing functionalities for electronics applications, by rational chemical design and appropriate combination of device constituents. The unique electronic structure of a molecular solid is characterized as (i) anisotropic electrostatic fields that originate from molecular quadrupoles, (ii) interfacial energy-level lineup governed by simple electrostatics, and (iii) weak intermolecular interactions that make not only structural order but also energy distributions of the frontier orbitals sensitive to atmosphere and interface growth. This article shows an overview on these features with reference to the improved understanding of the orientation-dependent electronic structure, comprehensive mechanisms of molecular doping, and energy-level alignment. Furthermore, the engineering of ionization energy by the control of the electrostatic fields and work function of practical electrodes by contact-induced doping is briefly described for the purpose of highlighting how the electronic structure impacts the performance of organic devices.

Establishing conditions for simulating hydrophobic solutes in electric fields by molecular dynamics: effects of the long-range van der Waals treatment on the apparent particle mobility.

PubMed

Miličević, Zoran; Marrink, Siewert J; Smith, Ana-Sunčana; Smith, David M

2014-08-01

Despite considerable effort over the last decade, the interactions between solutes and solvents in the presence of electric fields have not yet been fully understood. A very useful manner in which to study these systems is through the application of molecular dynamics (MD) simulations. However, a number of MD studies have shown a tremendous sensitivity of the migration rate of a hydrophobic solute to the treatment of the long range part of the van der Waals interactions. While the origin of this sensitivity was never explained, the mobility is currently regarded as an artifact of an improper simulation setup. We explain the spread in observed mobilites by performing extensive molecular dynamics simulations using the GROMACS software package on a system consisting of a model hydrophobic object (Lennard-Jones particle) immersed in water both in the presence and absence of a static electric field. We retrieve a unidirectional field-induced mobility of the hydrophobic object when the forces are simply truncated. Careful analysis of the data shows that, only in the specific case of truncated forces, a non-zero van der Waals force acts, on average, on the Lennard-Jones particle. Using the Stokes law we demonstrate that this force yields quantitative agreement with the field-induced mobility found within this setup. In contrast, when the treatment of forces is continuous, no net force is observed. In this manner, we provide a simple explanation for the previously controversial reports.

Carbohydrate-protein interactions: molecular modeling insights.

PubMed

Pérez, Serge; Tvaroška, Igor

2014-01-01

The article reviews the significant contributions to, and the present status of, applications of computational methods for the characterization and prediction of protein-carbohydrate interactions. After a presentation of the specific features of carbohydrate modeling, along with a brief description of the experimental data and general features of carbohydrate-protein interactions, the survey provides a thorough coverage of the available computational methods and tools. At the quantum-mechanical level, the use of both molecular orbitals and density-functional theory is critically assessed. These are followed by a presentation and critical evaluation of the applications of semiempirical and empirical methods: QM/MM, molecular dynamics, free-energy calculations, metadynamics, molecular robotics, and others. The usefulness of molecular docking in structural glycobiology is evaluated by considering recent docking- validation studies on a range of protein targets. The range of applications of these theoretical methods provides insights into the structural, energetic, and mechanistic facets that occur in the course of the recognition processes. Selected examples are provided to exemplify the usefulness and the present limitations of these computational methods in their ability to assist in elucidation of the structural basis underlying the diverse function and biological roles of carbohydrates in their dialogue with proteins. These test cases cover the field of both carbohydrate biosynthesis and glycosyltransferases, as well as glycoside hydrolases. The phenomenon of (macro)molecular recognition is illustrated for the interactions of carbohydrates with such proteins as lectins, monoclonal antibodies, GAG-binding proteins, porins, and viruses. © 2014 Elsevier Inc. All rights reserved.

Aluminium in Biological Environments: A Computational Approach

PubMed Central

Mujika, Jon I; Rezabal, Elixabete; Mercero, Jose M; Ruipérez, Fernando; Costa, Dominique; Ugalde, Jesus M; Lopez, Xabier

2014-01-01

The increased availability of aluminium in biological environments, due to human intervention in the last century, raises concerns on the effects that this so far “excluded from biology” metal might have on living organisms. Consequently, the bioinorganic chemistry of aluminium has emerged as a very active field of research. This review will focus on our contributions to this field, based on computational studies that can yield an understanding of the aluminum biochemistry at a molecular level. Aluminium can interact and be stabilized in biological environments by complexing with both low molecular mass chelants and high molecular mass peptides. The speciation of the metal is, nonetheless, dictated by the hydrolytic species dominant in each case and which vary according to the pH condition of the medium. In blood, citrate and serum transferrin are identified as the main low molecular mass and high molecular mass molecules interacting with aluminium. The complexation of aluminium to citrate and the subsequent changes exerted on the deprotonation pathways of its tritable groups will be discussed along with the mechanisms for the intake and release of aluminium in serum transferrin at two pH conditions, physiological neutral and endosomatic acidic. Aluminium can substitute other metals, in particular magnesium, in protein buried sites and trigger conformational disorder and alteration of the protonation states of the protein's sidechains. A detailed account of the interaction of aluminium with proteic sidechains will be given. Finally, it will be described how alumnium can exert oxidative stress by stabilizing superoxide radicals either as mononuclear aluminium or clustered in boehmite. The possibility of promotion of Fenton reaction, and production of hydroxyl radicals will also be discussed. PMID:24757505

Anomalous transport of charged dust grains in a magnetized collisional plasma: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Bezbaruah, Pratikshya; Das, Nilakshi

2018-05-01

Anomalous diffusion of charged dust grains immersed in a plasma in the presence of strong ion-neutral collision, flowing ions, and a magnetic field has been observed. Molecular Dynamics simulation confirms the deviation from normal diffusion in an ensemble of dust grains probed in laboratory plasma chambers. Collisional effects are significant in governing the nature of diffusion. In order to have a clear idea on the transport of particles in a real experimental situation, the contribution of streaming ions and the magnetic field along with collision is considered through the relevant interaction potential. The nonlinear evolution of Mean Square Displacement is an indication of the modification in particle trajectories due to several effects as mentioned above. It is found that strong collision and ion flow significantly affect the interparticle interaction potential in the presence of the magnetic field and lead to the appearance of the asymmetric type of Debye Hückel (D H) potential. Due to the combined effect of the magnetic field, ion flow, and collision, dusty plasma exhibits a completely novel behavior. The coupling parameter Γ enhances the asymmetric D H type potential arising due to ion flow, and this may drive the system to a disordered state.

Removing systematic errors in interionic potentials of mean force computed in molecular simulations using reaction-field-based electrostatics

PubMed Central

Baumketner, Andrij

2009-01-01

The performance of reaction-field methods to treat electrostatic interactions is tested in simulations of ions solvated in water. The potential of mean force between sodium chloride pair of ions and between side chains of lysine and aspartate are computed using umbrella sampling and molecular dynamics simulations. It is found that in comparison with lattice sum calculations, the charge-group-based approaches to reaction-field treatments produce a large error in the association energy of the ions that exhibits strong systematic dependence on the size of the simulation box. The atom-based implementation of the reaction field is seen to (i) improve the overall quality of the potential of mean force and (ii) remove the dependence on the size of the simulation box. It is suggested that the atom-based truncation be used in reaction-field simulations of mixed media. PMID:19292522

Intensity enhancement and selective detection of proximate solvent molecules by molecular near-field effect in resonance hyper-Raman scattering

NASA Astrophysics Data System (ADS)

Shimada, Rintaro; Kano, Hideaki; Hamaguchi, Hiro-o.

2008-07-01

A new molecular phenomenon associated with resonance hyper-Raman (HR) scattering in solution has been discovered. Resonance HR spectra of all-trans-β-carotene and all-trans-lycopene in various solvents exhibited several extra bands that were not assignable to the solute but were unequivocally assigned to the solvents. Neat solvents did not show detectable HR signals under the same experimental conditions. Similar experiments with all-trans-retinal did not exhibit such enhancement either. All-trans-β-carotene and all-trans-lycopene have thus been shown to induce enhanced HR scattering of solvent molecules through a novel molecular effect that is not associated with all-trans-retinal. We call this new effect the "molecular near-field effect." In order to explain this newly found effect, an extended vibronic theory of resonance HR scattering is developed where the vibronic interaction including the proximate solvent molecule (intermolecular vibronic coupling) is explicitly introduced in the solute hyperpolarizability tensor. The potential of "molecular near-field HR spectroscopy," which selectively detects molecules existing in the close vicinity of a HR probe in complex chemical or biological systems, is discussed.

Analysis of nanoscale two-phase flow of argon using molecular dynamics

NASA Astrophysics Data System (ADS)

Verma, Abhishek Kumar; Kumar, Rakesh

2014-12-01

Two phase flows through micro and nanochannels have attracted a lot of attention because of their immense applicability to many advanced fields such as MEMS/NEMS, electronic cooling, bioengineering etc. In this work, a molecular dynamics simulation method is employed to study the condensation process of superheated argon vapor force driven flow through a nanochannel combining fluid flow and heat transfer. A simple and effective particle insertion method is proposed to model phase change of argon based on non-periodic boundary conditions in the simulation domain. Starting from a crystalline solid wall of channel, the condensation process evolves from a transient unsteady state where we study the influence of different wall temperatures and fluid wall interactions on interfacial and heat transport properties of two phase flows. Subsequently, we analyzed transient temperature, density and velocity fields across the channel and their dependency on varying wall temperature and fluid wall interaction, after a dynamic equilibrium is achieved in phase transition. Quasi-steady nonequilibrium temperature profile, heat flux and interfacial thermal resistance were analyzed. The results demonstrate that the molecular dynamics method, with the proposed particle insertion method, effectively solves unsteady nonequilibrium two phase flows at nanoscale resolutions whose interphase between liquid and vapor phase is typically of the order of a few molecular diameters.

Toward the identification of a reliable 3D-QSAR model for the protein tyrosine phosphatase 1B inhibitors

NASA Astrophysics Data System (ADS)

Wang, Fangfang; Zhou, Bo

2018-04-01

Protein tyrosine phosphatase 1B (PTP1B) is an intracellular non-receptor phosphatase that is implicated in signal transduction of insulin and leptin pathways, thus PTP1B is considered as potential target for treating type II diabetes and obesity. The present article is an attempt to formulate the three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling of a series of compounds possessing PTP1B inhibitory activities using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The optimum template ligand-based models are statistically significant with great CoMFA (R2cv = 0.600, R2pred = 0.6760) and CoMSIA (R2cv = 0.624, R2pred = 0.8068) values. Molecular docking was employed to elucidate the inhibitory mechanisms of this series of compounds against PTP1B. In addition, the CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of PTP1B active site. The knowledge of structure-activity relationship and ligand-receptor interactions from 3D-QSAR model and molecular docking will be useful for better understanding the mechanism of ligand-receptor interaction and facilitating development of novel compounds as potent PTP1B inhibitors.

Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

PubMed Central

Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

2016-01-01

2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

Ab Initio Molecular Dynamics and Lattice Dynamics-Based Force Field for Modeling Hexagonal Boron Nitride in Mechanical and Interfacial Applications.

PubMed

Govind Rajan, Ananth; Strano, Michael S; Blankschtein, Daniel

2018-04-05

Hexagonal boron nitride (hBN) is an up-and-coming two-dimensional material, with applications in electronic devices, tribology, and separation membranes. Herein, we utilize density-functional-theory-based ab initio molecular dynamics (MD) simulations and lattice dynamics calculations to develop a classical force field (FF) for modeling hBN. The FF predicts the crystal structure, elastic constants, and phonon dispersion relation of hBN with good accuracy and exhibits remarkable agreement with the interlayer binding energy predicted by random phase approximation calculations. We demonstrate the importance of including Coulombic interactions but excluding 1-4 intrasheet interactions to obtain the correct phonon dispersion relation. We find that improper dihedrals do not modify the bulk mechanical properties and the extent of thermal vibrations in hBN, although they impact its flexural rigidity. Combining the FF with the accurate TIP4P/Ice water model yields excellent agreement with interaction energies predicted by quantum Monte Carlo calculations. Our FF should enable an accurate description of hBN interfaces in classical MD simulations.

Detection of electrically neutral and nonpolar molecules in ionic solutions using silicon nanowires

NASA Astrophysics Data System (ADS)

Wu, Ying-Pin; Chu, Chia-Jung; Tsai, Li-Chu; Su, Ya-Wen; Chen, Pei-Hua; Moodley, Mathew K.; Huang, Ding; Chen, Yit-Tsong; Yang, Ying-Jay; Chen, Chii-Dong

2017-04-01

We report on a technique that can extend the use of nanowire sensors to the detection of interactions involving nonpolar and neutral molecules in an ionic solution environment. This technique makes use of the fact that molecular interactions result in a change in the permittivity of the molecules involved. For the interactions taking place at the surface of nanowires, this permittivity change can be determined from the analysis of the measured complex impedance of the nanowire. To demonstrate this technique, histidine was detected using different charge polarities controlled by the pH value of the solution. This included the detection of electrically neutral histidine at a sensitivity of 1 pM. Furthermore, it is shown that nonpolar molecules, such as hexane, can also be detected. The technique is applicable to the use of nanowires with and without a surface-insulating oxide. We show that information about the changes in amplitude and the phase of the complex impedance reveals the fundamental characteristics of the molecular interactions, including the molecular field and the permittivity.

Molecular modeling in structural nano-toxicology: interactions of nano-particles with nano-machinery of cells.

PubMed

Yanamala, Naveena; Kagan, Valerian E; Shvedova, Anna A

2013-12-01

Over the past two decades, nanotechnology has emerged as a key player in various disciplines of science and technology. Some of the most exciting applications are in the field of biomedicine - for theranostics (for combined diagnostic and therapeutic purposes) as well as for exploration of biological systems. A detailed understanding of the molecular interactions between nanoparticles and biological nano-machinery - macromolecules, membranes, and intracellular organelles - is crucial for obtaining adequate information on mechanisms of action of nanomaterials as well as a perspective on the long term effects of these materials and their possible toxicological outcomes. This review focuses on the use of structure-based computational molecular modeling as a tool to understand and to predict the interactions between nanomaterials and nano-biosystems. We review major approaches and provide examples of computational analysis of the structural principles behind such interactions. A rationale on how nanoparticles of different sizes, shape, structure and chemical properties can affect the organization and functions of nano-machinery of cells is also presented. Published by Elsevier B.V.

Evaluation of synthetic linear motor-molecule actuation energetics

PubMed Central

Brough, Branden; Northrop, Brian H.; Schmidt, Jacob J.; Tseng, Hsian-Rong; Houk, Kendall N.; Stoddart, J. Fraser; Ho, Chih-Ming

2006-01-01

By applying atomic force microscope (AFM)-based force spectroscopy together with computational modeling in the form of molecular force-field simulations, we have determined quantitatively the actuation energetics of a synthetic motor-molecule. This multidisciplinary approach was performed on specifically designed, bistable, redox-controllable [2]rotaxanes to probe the steric and electrostatic interactions that dictate their mechanical switching at the single-molecule level. The fusion of experimental force spectroscopy and theoretical computational modeling has revealed that the repulsive electrostatic interaction, which is responsible for the molecular actuation, is as high as 65 kcal·mol−1, a result that is supported by ab initio calculations. PMID:16735470

The Role of Epigenomics in Aquatic Toxicology

EPA Science Inventory

Over the past decade, the field of molecular biology has rapidly incorporated epigenetic studies to evaluate organism–environment interactions that can result in chronic effects. Such responses arise from early life stage stress, the utilization of genetic information over ...

Dynamical photo-induced electronic properties of molecular junctions

NASA Astrophysics Data System (ADS)

Beltako, K.; Michelini, F.; Cavassilas, N.; Raymond, L.

2018-03-01

Nanoscale molecular-electronic devices and machines are emerging as promising functional elements, naturally flexible and efficient, for next-generation technologies. A deeper understanding of carrier dynamics in molecular junctions is expected to benefit many fields of nanoelectronics and power devices. We determine time-resolved charge current flowing at the donor-acceptor interface in molecular junctions connected to metallic electrodes by means of quantum transport simulations. The current is induced by the interaction of the donor with a Gaussian-shape femtosecond laser pulse. Effects of the molecular internal coupling, metal-molecule tunneling, and light-donor coupling on photocurrent are discussed. We then define the time-resolved local density of states which is proposed as an efficient tool to describe the absorbing molecule in contact with metallic electrodes. Non-equilibrium reorganization of hybridized molecular orbitals through the light-donor interaction gives rise to two phenomena: the dynamical Rabi shift and the appearance of Floquet-like states. Such insights into the dynamical photoelectronic structure of molecules are of strong interest for ultrafast spectroscopy and open avenues toward the possibility of analyzing and controlling the internal properties of quantum nanodevices with pump-push photocurrent spectroscopy.

A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: Multi-center molecular Ornstein-Zernike self-consistent field approach

NASA Astrophysics Data System (ADS)

Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

2015-07-01

In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl- + CH3Cl → ClCH3 + Cl-) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: multi-center molecular Ornstein-Zernike self-consistent field approach.

PubMed

Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

2015-07-07

In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl(-) + CH3Cl → ClCH3 + Cl(-)) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

Dynamics of relaxation to a stationary state for interacting molecular motors

NASA Astrophysics Data System (ADS)

Gomes, Luiza V. F.; Kolomeisky, Anatoly B.

2018-01-01

Motor proteins are active enzymatic molecules that drive a variety of biological processes, including transfer of genetic information, cellular transport, cell motility and muscle contraction. It is known that these biological molecular motors usually perform their cellular tasks by acting collectively, and there are interactions between individual motors that specify the overall collective behavior. One of the fundamental issues related to the collective dynamics of motor proteins is the question if they function at stationary-state conditions. To investigate this problem, we analyze a relaxation to the stationary state for the system of interacting molecular motors. Our approach utilizes a recently developed theoretical framework, which views the collective dynamics of motor proteins as a totally asymmetric simple exclusion process of interacting particles, where interactions are taken into account via a thermodynamically consistent approach. The dynamics of relaxation to the stationary state is analyzed using a domain-wall method that relies on a mean-field description, which takes into account some correlations. It is found that the system quickly relaxes for repulsive interactions, while attractive interactions always slow down reaching the stationary state. It is also predicted that for some range of parameters the fastest relaxation might be achieved for a weak repulsive interaction. Our theoretical predictions are tested with Monte Carlo computer simulations. The implications of our findings for biological systems are briefly discussed.

The complex nature of calcium cation interactions with phospholipid bilayers

PubMed Central

Melcrová, Adéla; Pokorna, Sarka; Pullanchery, Saranya; Kohagen, Miriam; Jurkiewicz, Piotr; Hof, Martin; Jungwirth, Pavel; Cremer, Paul S.; Cwiklik, Lukasz

2016-01-01

Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles in calcium-containing environments. To gain additional atomic-level information, the experiments are complemented by molecular simulations that utilize an accurate force field for calcium ions with scaled charges effectively accounting for electronic polarization effects. We demonstrate that lipid membranes have substantial calcium-binding capacity, with several types of binding sites present. Significantly, the binding mode depends on calcium concentration with important implications for calcium buffering, synaptic plasticity, and protein-membrane association. PMID:27905555

The complex nature of calcium cation interactions with phospholipid bilayers

NASA Astrophysics Data System (ADS)

Melcrová, Adéla; Pokorna, Sarka; Pullanchery, Saranya; Kohagen, Miriam; Jurkiewicz, Piotr; Hof, Martin; Jungwirth, Pavel; Cremer, Paul S.; Cwiklik, Lukasz

2016-12-01

Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles in calcium-containing environments. To gain additional atomic-level information, the experiments are complemented by molecular simulations that utilize an accurate force field for calcium ions with scaled charges effectively accounting for electronic polarization effects. We demonstrate that lipid membranes have substantial calcium-binding capacity, with several types of binding sites present. Significantly, the binding mode depends on calcium concentration with important implications for calcium buffering, synaptic plasticity, and protein-membrane association.

Recent opportunities for an increasing role for physical explanations in biology.

PubMed

Morange, Michel

2011-06-01

Relations between physics and biology have been always difficult. One reason is that physical approaches to the phenomena of life have frequently been conceived by their authors as alternatives to biological explanations. My argument is that molecular descriptions and explanations have been pushed so far that they have reached their limits: these limits constitute a favourable niche in which physical explanations can develop. I will focus on the field of molecular and cell biology and give many examples of these recent physical studies made possible by the precision of molecular observations. The nature of these niches is probably diverse. I consider that it is too early to have a global view of the interactions between biological and physical explanations, and to organize them into different categories. Such interactions are not new within the life sciences: the history of biology reveals a complex, permanently moving landscape of interactions between biological and physical explanations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Theory of molecular rate processes in the presence of intense laser radiation

NASA Technical Reports Server (NTRS)

George, T. F.; Zimmerman, I. H.; Devries, P. L.; Yuan, J.-M.; Lam, K.-S.; Bellum, J. C.; Lee, H.-W.; Slutsky, M. S.; Lin, J.-T.

1979-01-01

The present paper deals with the influence of intense laser radiation on gas-phase molecular rate processes. Representations of the radiation field, the particle system, and the interaction involving these two entities are discussed from a general rather than abstract point of view. The theoretical methods applied are outlined, and the formalism employed is illustrated by application to a variety of specific processes. Quantum mechanical and semiclassical treatments of representative atom-atom and atom-diatom collision processes in the presence of a field are examined, and examples of bound-continuum processes and heterogeneous catalysis are discussed within the framework of both quantum-mechanical and semiclassical theories.

qPIPSA: Relating enzymatic kinetic parameters and interaction fields

PubMed Central

Gabdoulline, Razif R; Stein, Matthias; Wade, Rebecca C

2007-01-01

Background The simulation of metabolic networks in quantitative systems biology requires the assignment of enzymatic kinetic parameters. Experimentally determined values are often not available and therefore computational methods to estimate these parameters are needed. It is possible to use the three-dimensional structure of an enzyme to perform simulations of a reaction and derive kinetic parameters. However, this is computationally demanding and requires detailed knowledge of the enzyme mechanism. We have therefore sought to develop a general, simple and computationally efficient procedure to relate protein structural information to enzymatic kinetic parameters that allows consistency between the kinetic and structural information to be checked and estimation of kinetic constants for structurally and mechanistically similar enzymes. Results We describe qPIPSA: quantitative Protein Interaction Property Similarity Analysis. In this analysis, molecular interaction fields, for example, electrostatic potentials, are computed from the enzyme structures. Differences in molecular interaction fields between enzymes are then related to the ratios of their kinetic parameters. This procedure can be used to estimate unknown kinetic parameters when enzyme structural information is available and kinetic parameters have been measured for related enzymes or were obtained under different conditions. The detailed interaction of the enzyme with substrate or cofactors is not modeled and is assumed to be similar for all the proteins compared. The protein structure modeling protocol employed ensures that differences between models reflect genuine differences between the protein sequences, rather than random fluctuations in protein structure. Conclusion Provided that the experimental conditions and the protein structural models refer to the same protein state or conformation, correlations between interaction fields and kinetic parameters can be established for sets of related enzymes. Outliers may arise due to variation in the importance of different contributions to the kinetic parameters, such as protein stability and conformational changes. The qPIPSA approach can assist in the validation as well as estimation of kinetic parameters, and provide insights into enzyme mechanism. PMID:17919319

Cell Division in genus Corynebacterium: protein-protein interaction and molecular docking of SepF and FtsZ in the understanding of cytokinesis in pathogenic species.

PubMed

Oliveira, Alberto F; Folador, Edson L; Gomide, Anne C P; Goes-Neto, Aristóteles; Azevedo, Vasco A C; Wattam, Alice R

2018-02-15

The genus Corynebacterium includes species of great importance in medical, veterinary and biotechnological fields. The genus-specific families (PLfams) from PATRIC have been used to observe conserved proteins associated to all species. Our results showed a large number of conserved proteins that are associated with the cellular division process. Was not observe in our results other proteins like FtsA and ZapA that interact with FtsZ. Our findings point that SepF overlaps the function of this proteins explored by molecular docking, protein-protein interaction and sequence analysis. Transcriptomic analysis showed that these two (Sepf and FtsZ) proteins can be expressed in different conditions together. The work presents novelties on molecules participating in the cell division event, from the interaction of FtsZ and SepF, as new therapeutic targets.

Efficient Relaxation of Protein-Protein Interfaces by Discrete Molecular Dynamics Simulations.

PubMed

Emperador, Agusti; Solernou, Albert; Sfriso, Pedro; Pons, Carles; Gelpi, Josep Lluis; Fernandez-Recio, Juan; Orozco, Modesto

2013-02-12

Protein-protein interactions are responsible for the transfer of information inside the cell and represent one of the most interesting research fields in structural biology. Unfortunately, after decades of intense research, experimental approaches still have difficulties in providing 3D structures for the hundreds of thousands of interactions formed between the different proteins in a living organism. The use of theoretical approaches like docking aims to complement experimental efforts to represent the structure of the protein interactome. However, we cannot ignore that current methods have limitations due to problems of sampling of the protein-protein conformational space and the lack of accuracy of available force fields. Cases that are especially difficult for prediction are those in which complex formation implies a non-negligible change in the conformation of the interacting proteins, i.e., those cases where protein flexibility plays a key role in protein-protein docking. In this work, we present a new approach to treat flexibility in docking by global structural relaxation based on ultrafast discrete molecular dynamics. On a standard benchmark of protein complexes, the method provides a general improvement over the results obtained by rigid docking. The method is especially efficient in cases with large conformational changes upon binding, in which structure relaxation with discrete molecular dynamics leads to a predictive success rate double that obtained with state-of-the-art rigid-body docking.

The emerging genomics and systems biology research lead to systems genomics studies.

PubMed

Yang, Mary Qu; Yoshigoe, Kenji; Yang, William; Tong, Weida; Qin, Xiang; Dunker, A; Chen, Zhongxue; Arbania, Hamid R; Liu, Jun S; Niemierko, Andrzej; Yang, Jack Y

2014-01-01

Synergistically integrating multi-layer genomic data at systems level not only can lead to deeper insights into the molecular mechanisms related to disease initiation and progression, but also can guide pathway-based biomarker and drug target identification. With the advent of high-throughput next-generation sequencing technologies, sequencing both DNA and RNA has generated multi-layer genomic data that can provide DNA polymorphism, non-coding RNA, messenger RNA, gene expression, isoform and alternative splicing information. Systems biology on the other hand studies complex biological systems, particularly systematic study of complex molecular interactions within specific cells or organisms. Genomics and molecular systems biology can be merged into the study of genomic profiles and implicated biological functions at cellular or organism level. The prospectively emerging field can be referred to as systems genomics or genomic systems biology. The Mid-South Bioinformatics Centre (MBC) and Joint Bioinformatics Ph.D. Program of University of Arkansas at Little Rock and University of Arkansas for Medical Sciences are particularly interested in promoting education and research advancement in this prospectively emerging field. Based on past investigations and research outcomes, MBC is further utilizing differential gene and isoform/exon expression from RNA-seq and co-regulation from the ChiP-seq specific for different phenotypes in combination with protein-protein interactions, and protein-DNA interactions to construct high-level gene networks for an integrative genome-phoneme investigation at systems biology level.

A theoretical thermochemical study of solute-solvent dielectric effects in the displacement of codon-anticodon base pairs

NASA Astrophysics Data System (ADS)

Monajjemi, M.; Razavian, M. H.; Mollaamin, F.; Naderi, F.; Honarparvar, B.

2008-12-01

Quantum-chemical solvent effect theories describe the electronic structure of a molecular subsystem embedded in a solvent or other molecular environment. The solvation of biomolecules is important in molecular biology, since numerous processes involve proteins interacting in changing solvent-solute systems. In this theoretical study, we focus on mRNA-tRNA base pairs as a fundamental step in protein synthesis influenced by hydrogen bonding between two antiparallel trinucleotides, namely, the mRNA codon and tRNA anticodon. We use the mean reaction field theories, which describe electrostatic and polarization interactions between solute and solvent in the AAA, UUU, AAG, and UUC triplex sequences optimized in various solvent media such as water, dimethylsulfoxide, methanol, ethanol, and cyclopean using the self-consistent reaction field model. This process depends on either the reaction potential function of the solvent or charge transfer operators that appear in solute-solvent interaction. Because of codon and anticodon biological criteria, we performed nonempirical quantum-mechanical calculations at the BLYP and B3LYP/3-21G, 6-31G, and 6-31G* levels of theory in the gas phase and five solvents at three temperatures. Finally, to obtain more information, we calculated thermochemical parameters to find that the dielectric constant of solvents plays an important role in the displacement of amino acid sequences on codon-anticodon residues in proteins, which can cause some mutations in humans.

Hydration and Ion Pairing in Aqueous Mg2+ and Zn2+ Solutions: Force-Field Description Aided by Neutron Scattering Experiments and Ab Initio Molecular Dynamics Simulations.

PubMed

Duboué-Dijon, Elise; Mason, Philip E; Fischer, Henry E; Jungwirth, Pavel

2018-04-05

Magnesium and zinc dications possess the same charge and have an almost identical size, yet they behave very differently in aqueous solutions and play distinct biological roles. It is thus crucial to identify the origins of such different behaviors and to assess to what extent they can be captured by force-field molecular dynamics simulations. In this work, we combine neutron scattering experiments in a specific mixture of H 2 O and D 2 O (the so-called null water) with ab initio molecular dynamics simulations to probe the difference in the hydration structure and ion-pairing properties of chloride solutions of the two cations. The obtained data are used as a benchmark to develop a scaled-charge force field for Mg 2+ that includes electronic polarization in a mean field way. We show that using this electronic continuum correction we can describe aqueous magnesium chloride solutions well. However, in aqueous zinc chloride specific interaction terms between the ions need to be introduced to capture ion pairing quantitatively.

An improved DNA force field for ssDNA interactions with gold nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Xiankai; Huai, Ping; Fan, Chunhai

The widespread applications of single-stranded DNA (ssDNA) conjugated gold nanoparticles (AuNPs) have spurred an increasing interest in the interactions between ssDNA and AuNPs. Despite extensive studies using the most sophisticated experimental techniques, the detailed molecular mechanisms still remain largely unknown. Large scale molecular dynamics (MD) simulations can thus be used to supplement experiments by providing complementary information about ssDNA-AuNP interactions. However, up to now, all modern force fields for DNA were developed based on the properties of double-stranded DNA (dsDNA) molecules, which have hydrophilic outer backbones “protecting” hydrophobic inner nucleobases from water. Without the double-helix structure of dsDNA and thusmore » the “protection” by the outer backbone, the nucleobases of ssDNA are directly exposed to solvent, and their behavior in water is very different from that of dsDNA, especially at the interface with nanoparticles. In this work, we have improved the force field of ssDNA for use with nanoparticles, such as AuNPs, based on recent experimental results and quantum mechanics calculations. With the new improved force field, we demonstrated that a poly(A) sequence adsorbed on a AuNP surface is much more stable than a poly(T) sequence, which is consistent with recent experimental observations. On the contrary, the current standard force fields, including AMBER03, CHARMM27, and OPLSAA, all gave erroneous results as compared to experiments. The current improved force field is expected to have wide applications in the study of ssDNA with nanomaterials including AuNPs, which might help promote the development of ssDNA-based biosensors and other bionano-devices.« less

An improved DNA force field for ssDNA interactions with gold nanoparticles

NASA Astrophysics Data System (ADS)

Jiang, Xiankai; Gao, Jun; Huynh, Tien; Huai, Ping; Fan, Chunhai; Zhou, Ruhong; Song, Bo

2014-06-01

The widespread applications of single-stranded DNA (ssDNA) conjugated gold nanoparticles (AuNPs) have spurred an increasing interest in the interactions between ssDNA and AuNPs. Despite extensive studies using the most sophisticated experimental techniques, the detailed molecular mechanisms still remain largely unknown. Large scale molecular dynamics (MD) simulations can thus be used to supplement experiments by providing complementary information about ssDNA-AuNP interactions. However, up to now, all modern force fields for DNA were developed based on the properties of double-stranded DNA (dsDNA) molecules, which have hydrophilic outer backbones "protecting" hydrophobic inner nucleobases from water. Without the double-helix structure of dsDNA and thus the "protection" by the outer backbone, the nucleobases of ssDNA are directly exposed to solvent, and their behavior in water is very different from that of dsDNA, especially at the interface with nanoparticles. In this work, we have improved the force field of ssDNA for use with nanoparticles, such as AuNPs, based on recent experimental results and quantum mechanics calculations. With the new improved force field, we demonstrated that a poly(A) sequence adsorbed on a AuNP surface is much more stable than a poly(T) sequence, which is consistent with recent experimental observations. On the contrary, the current standard force fields, including AMBER03, CHARMM27, and OPLSAA, all gave erroneous results as compared to experiments. The current improved force field is expected to have wide applications in the study of ssDNA with nanomaterials including AuNPs, which might help promote the development of ssDNA-based biosensors and other bionano-devices.

An improved DNA force field for ssDNA interactions with gold nanoparticles.

PubMed

Jiang, Xiankai; Gao, Jun; Huynh, Tien; Huai, Ping; Fan, Chunhai; Zhou, Ruhong; Song, Bo

2014-06-21

The widespread applications of single-stranded DNA (ssDNA) conjugated gold nanoparticles (AuNPs) have spurred an increasing interest in the interactions between ssDNA and AuNPs. Despite extensive studies using the most sophisticated experimental techniques, the detailed molecular mechanisms still remain largely unknown. Large scale molecular dynamics (MD) simulations can thus be used to supplement experiments by providing complementary information about ssDNA-AuNP interactions. However, up to now, all modern force fields for DNA were developed based on the properties of double-stranded DNA (dsDNA) molecules, which have hydrophilic outer backbones "protecting" hydrophobic inner nucleobases from water. Without the double-helix structure of dsDNA and thus the "protection" by the outer backbone, the nucleobases of ssDNA are directly exposed to solvent, and their behavior in water is very different from that of dsDNA, especially at the interface with nanoparticles. In this work, we have improved the force field of ssDNA for use with nanoparticles, such as AuNPs, based on recent experimental results and quantum mechanics calculations. With the new improved force field, we demonstrated that a poly(A) sequence adsorbed on a AuNP surface is much more stable than a poly(T) sequence, which is consistent with recent experimental observations. On the contrary, the current standard force fields, including AMBER03, CHARMM27, and OPLSAA, all gave erroneous results as compared to experiments. The current improved force field is expected to have wide applications in the study of ssDNA with nanomaterials including AuNPs, which might help promote the development of ssDNA-based biosensors and other bionano-devices.

Factors determining electrostatic fields in molecular dynamics simulations of the Ras/effector interface.

PubMed

Ensign, Daniel L; Webb, Lauren J

2011-12-01

Using molecular dynamics simulations, we explore geometric and physical factors contributing to calculated electrostatic fields at the binding surface of the GTPase Ras with a spectroscopically labeled variant of a downstream effector, the Ras-binding domain of Ral guanine nucleotide dissociation stimulator (RalGDS). A related system (differing by mutation of one amino acid) has been studied in our group using vibrational Stark effect spectroscopy, a technique sensitive to electrostatic fields. Electrostatic fields were computed using the AMBER 2003 force field and averaged over snapshots from molecular dynamics simulation. We investigate geometric factors by exploring how the orientation of the spectroscopic probe changes on Ras-effector binding. In addition, we explore the physical origin of electrostatic fields at our spectroscopic probe by comparing contributions to the field from discrete components of the system, such as explicit solvent, residues on the Ras surface, and residues on the RalGDS surface. These models support our experimental hypothesis that vibrational Stark shifts are caused by Ras binding to its effector and not the structural rearrangements of the effector surface or probe reorientation on Ras-effector binding, for at least some of our experimental probes. These calculations provide physical insight into the origin, magnitude, and importance of electrostatic fields in protein-protein interactions and suggest new experiments to probe the field's role in protein docking. Copyright © 2011 Wiley-Liss, Inc.

Study of crystal-field interaction in magnetic frustrated lead pyrochlore Gd2Pb2O7

NASA Astrophysics Data System (ADS)

Swarnakar, D.; Jana, Y. M.

2018-05-01

A fine tuning between the crystal field and the molecular field to adopt unique ground state in frustrated magnetic R2M2O7 pyrochlores structures is made by the variation of chemical pressure at R-site caused by substitution of nonmagnetic cation of M-site. Existence of larger cation at M-site increases the lattice parameter or nearest-neighbor bond distance between magnetic R-spins, and causes subtle changes to the local oxygen environment surrounding each R-ion, thereby reduces the chemical pressure at R-site which leads to a dramatic change in the crystal-field and molecular field. To investigate the effect of chemical pressure, the experimental results of powder magnetic susceptibility and isothermal magnetization of the frustrated compound Gd2Pb2O7 containing largest cation, e.g. lead (Pb), at M4+-sites were simulated and analyzed employing a D3d crystal-field (CF) and anisotropic molecular field at R-sites in the self- consistent mean-field approach. The second-ordered axial parameter B20 and total CF splitting of the ground multiplet Gd-ion in Gd2Pb2O7 are 477 cm-1 and 4.8 cm-1 respectively which are the lowest among their isomorphous counterparts, implying reduced effect of the crystal-field at Gd site in Gd2Pb2O7.

Reactive molecular dynamics of the initial oxidation stages of Ni111 in pure water: effect of an applied electric field.

PubMed

Assowe, O; Politano, O; Vignal, V; Arnoux, P; Diawara, B; Verners, O; van Duin, A C T

2012-12-06

Corrosion processes occurring in aqueous solutions are critically dependent upon the interaction between the metal electrode and the solvent. In this work, the interaction of a nickel substrate with water molecules has been investigated using reactive force field (ReaxFF) molecular dynamics simulations. This approach was originally developed by van Duin and co-workers to study hydrocarbon chemistry and the catalytic properties of organic compounds. To our knowledge, this method has not previously been used to study the corrosion of nickel. In this work, we studied the interaction of 480 molecules of water (ρ = 0.99 g·cm(-3)) with Ni(111) surfaces at 300 K. The results showed that a water "bilayer" was adsorbed on the nickel surface. In the absence of an applied electric field, no dissociation of water was observed. However, the nickel atoms at the surface were charged positively, whereas the first water layer was charged negatively, indicating the formation of an electric double layer. To study the corrosion of nickel in pure water, we introduced an external electric field between the metal and the solution. The electric field intensity varied between 10 and 20 MeV/cm. The presence of this electric field led to oxidation of the metal surface. The structural and morphological differences associated with the growth of this oxide film in the presence of the electric field were evaluated. The simulated atomic trajectories were used to analyze the atomic displacement during the reactive process. The growth of the oxide scale on the nickel surface was primarily due to the movement of anions toward the interior of the metal substrate and the migration of nickel toward the free surface. We found that increasing the electric field intensity sped up the corrosion of nickel. The results also showed that the oxide film thickness increased linearly with increasing electric field intensity.

Fragmentation of interstellar clouds and star formation

NASA Technical Reports Server (NTRS)

Silk, J.

1982-01-01

The principal issues are addressed: the fragmentation of molecular clouds into units of stellar mass and the impact of star formation on molecular clouds. The observational evidence for fragmentation is summarized, and the gravitational instability described of a uniform spherical cloud collapsing from rest. The implications are considered of a finite pressure for the minimum fragment mass that is attainable in opacity-limited fragmentation. The role of magnetic fields is discussed in resolving the angular momentum problem and in making the collapse anisotropic, with notable consequences for fragmentation theory. Interactions between fragments are described, with emphasis on the effect of protostellar winds on the ambient cloud matter and on inhibiting further star formation. Such interactions are likely to have profound consequences for regulating the rate of star formation and on the energetics and dynamics of molecular clouds.

ATK-ForceField: a new generation molecular dynamics software package

NASA Astrophysics Data System (ADS)

Schneider, Julian; Hamaekers, Jan; Chill, Samuel T.; Smidstrup, Søren; Bulin, Johannes; Thesen, Ralph; Blom, Anders; Stokbro, Kurt

2017-12-01

ATK-ForceField is a software package for atomistic simulations using classical interatomic potentials. It is implemented as a part of the Atomistix ToolKit (ATK), which is a Python programming environment that makes it easy to create and analyze both standard and highly customized simulations. This paper will focus on the atomic interaction potentials, molecular dynamics, and geometry optimization features of the software, however, many more advanced modeling features are available. The implementation details of these algorithms and their computational performance will be shown. We present three illustrative examples of the types of calculations that are possible with ATK-ForceField: modeling thermal transport properties in a silicon germanium crystal, vapor deposition of selenium molecules on a selenium surface, and a simulation of creep in a copper polycrystal.

PyBioMed: a python library for various molecular representations of chemicals, proteins and DNAs and their interactions.

PubMed

Dong, Jie; Yao, Zhi-Jiang; Zhang, Lin; Luo, Feijun; Lin, Qinlu; Lu, Ai-Ping; Chen, Alex F; Cao, Dong-Sheng

2018-03-20

With the increasing development of biotechnology and informatics technology, publicly available data in chemistry and biology are undergoing explosive growth. Such wealthy information in these data needs to be extracted and transformed to useful knowledge by various data mining methods. Considering the amazing rate at which data are accumulated in chemistry and biology fields, new tools that process and interpret large and complex interaction data are increasingly important. So far, there are no suitable toolkits that can effectively link the chemical and biological space in view of molecular representation. To further explore these complex data, an integrated toolkit for various molecular representation is urgently needed which could be easily integrated with data mining algorithms to start a full data analysis pipeline. Herein, the python library PyBioMed is presented, which comprises functionalities for online download for various molecular objects by providing different IDs, the pretreatment of molecular structures, the computation of various molecular descriptors for chemicals, proteins, DNAs and their interactions. PyBioMed is a feature-rich and highly customized python library used for the characterization of various complex chemical and biological molecules and interaction samples. The current version of PyBioMed could calculate 775 chemical descriptors and 19 kinds of chemical fingerprints, 9920 protein descriptors based on protein sequences, more than 6000 DNA descriptors from nucleotide sequences, and interaction descriptors from pairwise samples using three different combining strategies. Several examples and five real-life applications were provided to clearly guide the users how to use PyBioMed as an integral part of data analysis projects. By using PyBioMed, users are able to start a full pipelining from getting molecular data, pretreating molecules, molecular representation to constructing machine learning models conveniently. PyBioMed provides various user-friendly and highly customized APIs to calculate various features of biological molecules and complex interaction samples conveniently, which aims at building integrated analysis pipelines from data acquisition, data checking, and descriptor calculation to modeling. PyBioMed is freely available at http://projects.scbdd.com/pybiomed.html .

3D-QSAR (CoMFA, CoMSIA), molecular docking and molecular dynamics simulations study of 6-aryl-5-cyano-pyrimidine derivatives to explore the structure requirements of LSD1 inhibitors.

PubMed

Ding, Lina; Wang, Zhi-Zheng; Sun, Xu-Dong; Yang, Jing; Ma, Chao-Ya; Li, Wen; Liu, Hong-Min

2017-08-01

Recently, Histone Lysine Specific Demethylase 1 (LSD1) was regarded as a promising anticancer target for the novel drug discovery. And several small molecules as LSD1 inhibitors in different structures have been reported. In this work, we carried out a molecular modeling study on the 6-aryl-5-cyano-pyrimidine fragment LSD1 inhibitors using three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to generate 3D-QSAR models. The results show that the best CoMFA model has q 2 =0.802, r 2 ncv =0.979, and the best CoMSIA model has q 2 =0.799, r 2 ncv =0.982. The electrostatic, hydrophobic and H-bond donor fields play important roles in the models. Molecular docking studies predict the binding mode and the interactions between the ligand and the receptor protein. Molecular dynamics simulations results reveal that the complex of the ligand and the receptor protein are stable at 300K. All the results can provide us more useful information for our further drug design. Copyright © 2017. Published by Elsevier Ltd.

Measurements of trap dynamics of cold OH molecules using resonance-enhanced multiphoton ionization

NASA Astrophysics Data System (ADS)

Gray, John M.; Bossert, Jason A.; Shyur, Yomay; Lewandowski, H. J.

2017-08-01

Trapping cold, chemically important molecules with electromagnetic fields is a useful technique to study small molecules and their interactions. Traps provide long interaction times, which are needed to precisely examine these low-density molecular samples. However, the trapping fields lead to nonuniform molecular density distributions in these systems. Therefore, it is important to be able to experimentally characterize the spatial density distribution in the trap. Ionizing molecules at different locations in the trap using resonance-enhanced multiphoton ionization (REMPI) and detecting the resulting ions can be used to probe the density distribution even at the low density present in these experiments because of the extremely high efficiency of detection. Until recently, one of the most chemically important molecules, OH, did not have a convenient REMPI scheme identified. Here, we use a newly developed 1 +1' REMPI scheme to detect trapped cold OH molecules. We use this capability to measure the trap dynamics of the central density of the cloud and the density distribution. These types of measurements can be used to optimize loading of molecules into traps, as well as to help characterize the energy distribution, which is critical knowledge for interpreting molecular collision experiments.

Conformational Order in Aggregates of Conjugated Polymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, Nicholas E.; Kohlstedt, Kevin L.; Savoie, Brett M.

With the abundant variety and increasing chemical complexity of conjugated poly-friers proliferating the field of organic semiconductors, it has become increasingly important to correlate the polymer molecular structure with its mesoscale conformational and morphological attributes. For instance, it is unknown which combinations of chemical moieties and periodicities predictably produce mesoscale ordering. Interestingly) not all ordered morphologies result in efficient devices. In this work we have parametrized accurate classical force-fields and used these to compute the conformational and aggregation characteristics of single strands of common conjugated polymers. Molecular dynamics trajectories are shown to reproduce experimentally observed polymeric ordering, concluding that efficientmore » organic photovoltaic devices span a range of polymer conformational classes, and suggesting that the solution-phase morphologies have far-reaching effects. Encouragingly, these simulations indicate that despite the wide-range of conformational classes present in successful devices, local molecular ordering, and not long-range crystallinity, appears to be the necessary requirement for efficient devices. Finally, we examine what makes a "good" solvent for conjugated polymers, concluding that dispersive pi-electron solvent-polymer interactions, and not the electrostatic potential of the backbone interacting with the solvent, are what primarily determine a polymer's solubility in a particular solvent, and consequently its morphological characteristics.« less

Materials and Molecular Research Division annual report 1983

DOE Office of Scientific and Technical Information (OSTI.GOV)

Searcy, A.W.; Muller, R.H.; Peterson, C.V.

1984-07-01

Progress is reported in the following fields: materials sciences (metallurgy and ceramics, solid-state physics, materials chemistry), chemical sciences (fundamental interactions, processes and techniques), actinide chemistry, fossil energy, electrochemical energy storage systems, superconducting magnets, semiconductor materials and devices, and work for others. (DLC)

A New Paradigm for Creating Amino Acid Chirality

NASA Astrophysics Data System (ADS)

Boyd, Richard N.; Famiano, Michael A.; Kajino, Toshitaka; Onaka, Takashi

2018-06-01

The Supernova Neutrino Amino Acid Processing (SNAAP) model (1) selects left-handed amino acids via the interaction of electron anti-neutrinos with the N nuclei that have been oriented by the strong magnetic field. Within the amino acid molecules, the shielding tensor alters the local magnetic field, and this tensor is sensitive to the molecular chirality. The astrophysical object (2) that might supply the magnetic field and the neutrinos could be a core-collapse supernova, although there are problems with that site. A more likely candidate would be a close binary system consisting of a Wolf-Rayet star with a neutron star companion. The accretion disk that would form around the neutron star could enable dust formation, as well as meteoroids and planets, and the temperatures in the outer portions would accommodate amino acid formation. When the WR star explodes it provides the intense anti-neutrino flux, while the neutron star and the WR star provide the magnetic field. Quantum molecular calculations that included perturbation effects on the shielding tensor for nitrogen from the reorientation of the molecular electric dipole have been performed. They have found the amino acids moving in an external magnetic field to be physically distinct, so the anti-neutrinos from the WR star interacting with the N nuclei can perform a chirality dependent selection. An enantiomeric excess of a few percent has been found for isovaline in an aqueous environment. Alanine was found to have a comparable, but slightly lower, enantiomeric excess. This model suggests that our Solar System might have been created by a system such as this, as has also been suggested by recent measurements of unstable nuclides in our local environment.M.A. Famiano et al., Astrobiology 18, 190 (2018)R.N. Boyd et al., Astrophys. J. (in press), arXiv.org/abs/a802.08285

On Predicting the Crystal Structure of Energetic Materials From Quantum Mechanics

DTIC Science & Technology

2008-12-01

DE ABSTRACT A quantum-mechanically-based potential energy function that describes interactions of dimers of the explosive ...method is capable of producing force fields for interactions of the molecular crystalline explosive RDX, and appears to be suitable to enable reliable...Ridge, TN. Byrd, E.F.C., Scuseria, G.E., Chabalowski, C.F., 2004: “An ab initio study of solid nitromethane , HMX, RDX and CL20: Successes and

Towards molecular modeling of the impact of heparin-derived oligosaccharides on hIFN-γ binding

NASA Astrophysics Data System (ADS)

Lilkova, E.; Petkov, P.; Ilieva, N.; Litov, L.

2015-10-01

Human interferon gamma (hIFN-γ) is an important signalling molecule, which plays a key role in the formation and modulation of immune response. The role of the cytokine C-termini in the formation of a complex with the extracellular receptor is still controversial due to the lack of structural information about this domain. Moreover, the C-termini are also responsible for the high affinity interaction of hIFN-γ with the glycosaminoglicans heparan sulfate and heparin. This interaction can drastically change the properties and behaviour of the protein. We performed molecular dynamics simulations in order to model the structure of the hIFN-γ C-terminal part and the interaction of the cytokine with heparin-derived oligosaccharides. For this purpose we reconstructed the missing C-terminal amino acid residues and performed folding simulations to determine their conformation. In order to simulate the interaction with heparin-like fragments, we developed CHARMM 36 compatible force field for the sulfamate anion group that is present in the glucosamine sugar to complete the heparin and heparan sulfate force field. The new topology and parameters reproduce the available experimental structural properties of heparin-like fragments. The simulations show that the oligosaccharides quickly bind the IFN-γ C-termini and reduce their solvent accessible surface area.

Positional cloning in mice and its use for molecular dissection of inflammatory arthritis.

PubMed

Abe, Koichiro; Yu, Philipp

2009-02-01

One of the upcoming next quests in the field of genetics might be molecular dissection of the genetic and environmental components of human complex diseases. In humans, however, there are certain experimental limitations for identification of a single component of the complex interactions by genetic analyses. Experimental animals offer simplified models for genetic and environmental interactions in human complex diseases. In particular, mice are the best mammalian models because of a long history and ample experience for genetic analyses. Forward genetics, which includes genetic screen and subsequent positional cloning of the causative genes, is a powerful strategy to dissect a complex phenomenon without preliminarily molecular knowledge of the process. In this review, first, we describe a general scheme of positional cloning in mice. Next, recent accomplishments on the patho-mechanisms of inflammatory arthritis by forward genetics approaches are introduced; Positional cloning effort for skg, Ali5, Ali18, cmo, and lupo mutants are provided as examples for the application to human complex diseases. As seen in the examples, the identification of genetic factors by positional cloning in the mouse have potential in solving molecular complexity of gene-environment interactions in human complex diseases.

Effect of angular momentum alignment and strong magnetic fields on the formation of protostellar discs

NASA Astrophysics Data System (ADS)

Gray, William J.; McKee, Christopher F.; Klein, Richard I.

2018-01-01

Star-forming molecular clouds are observed to be both highly magnetized and turbulent. Consequently, the formation of protostellar discs is largely dependent on the complex interaction between gravity, magnetic fields, and turbulence. Studies of non-turbulent protostellar disc formation with realistic magnetic fields have shown that these fields are efficient in removing angular momentum from the forming discs, preventing their formation. However, once turbulence is included, discs can form in even highly magnetized clouds, although the precise mechanism remains uncertain. Here, we present several high-resolution simulations of turbulent, realistically magnetized, high-mass molecular clouds with both aligned and random turbulence to study the role that turbulence, misalignment, and magnetic fields have on the formation of protostellar discs. We find that when the turbulence is artificially aligned so that the angular momentum is parallel to the initial uniform field, no rotationally supported discs are formed, regardless of the initial turbulent energy. We conclude that turbulence and the associated misalignment between the angular momentum and the magnetic field are crucial in the formation of protostellar discs in the presence of realistic magnetic fields.

Methane Adsorption in Zr-Based MOFs: Comparison and Critical Evaluation of Force Fields

PubMed Central

2017-01-01

The search for nanoporous materials that are highly performing for gas storage and separation is one of the contemporary challenges in material design. The computational tools to aid these experimental efforts are widely available, and adsorption isotherms are routinely computed for huge sets of (hypothetical) frameworks. Clearly the computational results depend on the interactions between the adsorbed species and the adsorbent, which are commonly described using force fields. In this paper, an extensive comparison and in-depth investigation of several force fields from literature is reported for the case of methane adsorption in the Zr-based Metal–Organic Frameworks UiO-66, UiO-67, DUT-52, NU-1000, and MOF-808. Significant quantitative differences in the computed uptake are observed when comparing different force fields, but most qualitative features are common which suggests some predictive power of the simulations when it comes to these properties. More insight into the host–guest interactions is obtained by benchmarking the force fields with an extensive number of ab initio computed single molecule interaction energies. This analysis at the molecular level reveals that especially ab initio derived force fields perform well in reproducing the ab initio interaction energies. Finally, the high sensitivity of uptake predictions on the underlying potential energy surface is explored. PMID:29170687

A recipe for free-energy functionals of polarizable molecular fluids

NASA Astrophysics Data System (ADS)

Sundararaman, Ravishankar; Letchworth-Weaver, Kendra; Arias, T. A.

2014-04-01

Classical density-functional theory is the most direct approach to equilibrium structures and free energies of inhomogeneous liquids, but requires the construction of an approximate free-energy functional for each liquid of interest. We present a general recipe for constructing functionals for small-molecular liquids based only on bulk experimental properties and ab initio calculations of a single solvent molecule. This recipe combines the exact free energy of the non-interacting system with fundamental measure theory for the repulsive contribution and a weighted density functional for the short-ranged attractive interactions. We add to these ingredients a weighted polarization functional for the long-range correlations in both the rotational and molecular-polarizability contributions to the dielectric response. We also perform molecular dynamics calculations for the free energy of cavity formation and the high-field dielectric response, and show that our free-energy functional adequately describes these properties (which are key for accurate solvation calculations) for all three solvents in our study: water, chloroform, and carbon tetrachloride.

EuCo 2P 2: A Model Molecular-Field Helical Heisenberg Antiferromagnet

DOE PAGES

Sangeetha, N. S.; Cuervo-Reyes, Eduardo; Pandey, Abhishek; ...

2016-07-19

The metallic compound EuCo 2P 2 with the body-centered tetragonal ThCr 2Si 2 structure containing Eu spins-7/2 was previously shown from single-crystal neutron diffraction measurements to exhibit a helical antiferromagnetic (AFM) structure below T N=66.5 K with the helix axis along the c axis and with the ordered moments aligned within the ab plane. Here we report crystallography, electrical resistivity, heat capacity, magnetization, and magnetic susceptibility measurements on single crystals of this compound. We demonstrate that EuCo 2P 2 is a model molecular-field helical Heisenberg antiferromagnet from comparisons of the anisotropic magnetic susceptibility χ, high-field magnetization, and magnetic heat capacitymore » of EuCo 2P 2 single crystals at temperature T≤TN with the predictions of our recent formulation of molecular-field theory. Values of the Heisenberg exchange interactions between the Eu spins are derived from the data. The low-T magnetic heat capacity ~T 3 arising from spin-wave excitations with no anisotropy gap is calculated and found to be comparable to the lattice heat capacity. The density of states at the Fermi energy of EuCo 2P 2 and the related compound BaCo 2P 2 are found from the heat capacity data to be large, 10 and 16 states/eV per formula unit for EuCo 2P 2 and BaCo 2P 2, respectively. These values are enhanced by a factor of ~2.5 above those found from DFT electronic structure calculations for the two compounds. Additionally, the calculations also find ferromagnetic Eu–Eu exchange interactions within the ab plane and AFM interactions between Eu spins in nearest- and next-nearest planes, in agreement with the MFT analysis of χ ab(T≤TN).« less

EuCo 2P 2: A Model Molecular-Field Helical Heisenberg Antiferromagnet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sangeetha, N. S.; Cuervo-Reyes, Eduardo; Pandey, Abhishek

The metallic compound EuCo 2P 2 with the body-centered tetragonal ThCr 2Si 2 structure containing Eu spins-7/2 was previously shown from single-crystal neutron diffraction measurements to exhibit a helical antiferromagnetic (AFM) structure below T N=66.5 K with the helix axis along the c axis and with the ordered moments aligned within the ab plane. Here we report crystallography, electrical resistivity, heat capacity, magnetization, and magnetic susceptibility measurements on single crystals of this compound. We demonstrate that EuCo 2P 2 is a model molecular-field helical Heisenberg antiferromagnet from comparisons of the anisotropic magnetic susceptibility χ, high-field magnetization, and magnetic heat capacitymore » of EuCo 2P 2 single crystals at temperature T≤TN with the predictions of our recent formulation of molecular-field theory. Values of the Heisenberg exchange interactions between the Eu spins are derived from the data. The low-T magnetic heat capacity ~T 3 arising from spin-wave excitations with no anisotropy gap is calculated and found to be comparable to the lattice heat capacity. The density of states at the Fermi energy of EuCo 2P 2 and the related compound BaCo 2P 2 are found from the heat capacity data to be large, 10 and 16 states/eV per formula unit for EuCo 2P 2 and BaCo 2P 2, respectively. These values are enhanced by a factor of ~2.5 above those found from DFT electronic structure calculations for the two compounds. Additionally, the calculations also find ferromagnetic Eu–Eu exchange interactions within the ab plane and AFM interactions between Eu spins in nearest- and next-nearest planes, in agreement with the MFT analysis of χ ab(T≤TN).« less

Molecular description of α-keto-based inhibitors of cruzain with activity against Chagas disease combining 3D-QSAR studies and molecular dynamics.

PubMed

Saraiva, Ádria P B; Miranda, Ricardo M; Valente, Renan P P; Araújo, Jéssica O; Souza, Rutelene N B; Costa, Clauber H S; Oliveira, Amanda R S; Almeida, Michell O; Figueiredo, Antonio F; Ferreira, João E V; Alves, Cláudio Nahum; Honorio, Kathia M

2018-04-22

In this work, a group of α-keto-based inhibitors of the cruzain enzyme with anti-chagas activity was selected for a three-dimensional quantitative structure-activity relationship study (3D-QSAR) combined with molecular dynamics (MD). Firstly, statistical models based on Partial Least Square (PLS) regression were developed employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) descriptors. Validation parameters (q 2 and r 2 )for the models were, respectively, 0.910 and 0.997 (CoMFA) and 0.913 and 0.992 (CoMSIA). In addition, external validation for the models using a test group revealed r 2 pred  = 0.728 (CoMFA) and 0.971 (CoMSIA). The most relevant aspect in this study was the generation of molecular fields in both favorable and unfavorable regions based on the models developed. These fields are important to interpret modifications necessary to enhance the biological activities of the inhibitors. This analysis was restricted considering the inhibitors in a fixed conformation, not interacting with their target, the cruzain enzyme. Then, MD was employed taking into account important variables such as time and temperature. MD helped describe the behavior of the inhibitors and their properties showed similar results as those generated by QSAR-3D study. © 2018 John Wiley & Sons A/S.

Applying electric field to charged and polar particles between metallic plates: extension of the Ewald method.

PubMed

Takae, Kyohei; Onuki, Akira

2013-09-28

We develop an efficient Ewald method of molecular dynamics simulation for calculating the electrostatic interactions among charged and polar particles between parallel metallic plates, where we may apply an electric field with an arbitrary size. We use the fact that the potential from the surface charges is equivalent to the sum of those from image charges and dipoles located outside the cell. We present simulation results on boundary effects of charged and polar fluids, formation of ionic crystals, and formation of dipole chains, where the applied field and the image interaction are crucial. For polar fluids, we find a large deviation of the classical Lorentz-field relation between the local field and the applied field due to pair correlations along the applied field. As general aspects, we clarify the difference between the potential-fixed and the charge-fixed boundary conditions and examine the relationship between the discrete particle description and the continuum electrostatics.

Ab initio molecular orbital studies of the positive muon and muonium in 4-arylmethyleneamino-TEMPO derivatives

NASA Astrophysics Data System (ADS)

Briere, T. M.; Jeong, J.; Das, T. P.; Ohira, S.; Nagamine, K.

2000-08-01

The muon and muonium bonding sites of the 4-arylmethyleneamino-2,2,6,6-tetramethylpiperidin-1-yloxyl radical crystals with aryl groups consisting of biphenyl and 4-pyridyl were studied via ab initio Hartree-Fock theory. The hyperfine fields, including both intramolecular and intermolecular interactions, were calculated at the sites of interest and compared to zero field μSR results.

An atomic mean-field spin-orbit approach within exact two-component theory for a non-perturbative treatment of spin-orbit coupling

NASA Astrophysics Data System (ADS)

Liu, Junzi; Cheng, Lan

2018-04-01

An atomic mean-field (AMF) spin-orbit (SO) approach within exact two-component theory (X2C) is reported, thereby exploiting the exact decoupling scheme of X2C, the one-electron approximation for the scalar-relativistic contributions, the mean-field approximation for the treatment of the two-electron SO contribution, and the local nature of the SO interactions. The Hamiltonian of the proposed SOX2CAMF scheme comprises the one-electron X2C Hamiltonian, the instantaneous two-electron Coulomb interaction, and an AMF SO term derived from spherically averaged Dirac-Coulomb Hartree-Fock calculations of atoms; no molecular relativistic two-electron integrals are required. Benchmark calculations for bond lengths, harmonic frequencies, dipole moments, and electric-field gradients for a set of diatomic molecules containing elements across the periodic table show that the SOX2CAMF scheme offers a balanced treatment for SO and scalar-relativistic effects and appears to be a promising candidate for applications to heavy-element containing systems. SOX2CAMF coupled-cluster calculations of molecular properties for bismuth compounds (BiN, BiP, BiF, BiCl, and BiI) are also presented and compared with experimental results to further demonstrate the accuracy and applicability of the SOX2CAMF scheme.

A Generic Force Field for Protein Coarse-Grained Molecular Dynamics Simulation

PubMed Central

Gu, Junfeng; Bai, Fang; Li, Honglin; Wang, Xicheng

2012-01-01

Coarse-grained (CG) force fields have become promising tools for studies of protein behavior, but the balance of speed and accuracy is still a challenge in the research of protein coarse graining methodology. In this work, 20 CG beads have been designed based on the structures of amino acid residues, with which an amino acid can be represented by one or two beads, and a CG solvent model with five water molecules was adopted to ensure the consistence with the protein CG beads. The internal interactions in protein were classified according to the types of the interacting CG beads, and adequate potential functions were chosen and systematically parameterized to fit the energy distributions. The proposed CG force field has been tested on eight proteins, and each protein was simulated for 1000 ns. Even without any extra structure knowledge of the simulated proteins, the Cα root mean square deviations (RMSDs) with respect to their experimental structures are close to those of relatively short time all atom molecular dynamics simulations. However, our coarse grained force field will require further refinement to improve agreement with and persistence of native-like structures. In addition, the root mean square fluctuations (RMSFs) relative to the average structures derived from the simulations show that the conformational fluctuations of the proteins can be sampled. PMID:23203075

Mechanical design of DNA nanostructures

NASA Astrophysics Data System (ADS)

Castro, Carlos E.; Su, Hai-Jun; Marras, Alexander E.; Zhou, Lifeng; Johnson, Joshua

2015-03-01

Structural DNA nanotechnology is a rapidly emerging field that has demonstrated great potential for applications such as single molecule sensing, drug delivery, and templating molecular components. As the applications of DNA nanotechnology expand, a consideration of their mechanical behavior is becoming essential to understand how these structures will respond to physical interactions. This review considers three major avenues of recent progress in this area: (1) measuring and designing mechanical properties of DNA nanostructures, (2) designing complex nanostructures based on imposed mechanical stresses, and (3) designing and controlling structurally dynamic nanostructures. This work has laid the foundation for mechanically active nanomachines that can generate, transmit, and respond to physical cues in molecular systems.Structural DNA nanotechnology is a rapidly emerging field that has demonstrated great potential for applications such as single molecule sensing, drug delivery, and templating molecular components. As the applications of DNA nanotechnology expand, a consideration of their mechanical behavior is becoming essential to understand how these structures will respond to physical interactions. This review considers three major avenues of recent progress in this area: (1) measuring and designing mechanical properties of DNA nanostructures, (2) designing complex nanostructures based on imposed mechanical stresses, and (3) designing and controlling structurally dynamic nanostructures. This work has laid the foundation for mechanically active nanomachines that can generate, transmit, and respond to physical cues in molecular systems. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07153k

Committee on Atomic, Molecular and Optical Sciences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lancaster, James

The Committee on Atomic, Molecular, and Optical Sciences (CAMOS) is a standing activity of the National Research Council (NRC) that operates under the auspices of the Board on Physics and Astronomy. CAMOS is one of five standing committees of the BPA that are charged with assisting it in achieving its goals—monitoring the health of physics and astronomy, identifying important new developments at the scientific forefronts, fostering interactions with other fields, strengthening connections to technology, facilitating effective service to the nation, and enhancing education in physics. CAMOS provides these capabilities for the atomic, molecular and optical (AMO) sciences.

Molecular evidence of stereo-specific lactoferrin dimers in solution.

PubMed

Persson, Björn A; Lund, Mikael; Forsman, Jan; Chatterton, Dereck E W; Akesson, Torbjörn

2010-10-01

Gathering experimental evidence suggests that bovine as well as human lactoferrin self-associate in aqueous solution. Still, a molecular level explanation is unavailable. Using force field based molecular modeling of the protein-protein interaction free energy we demonstrate (1) that lactoferrin forms highly stereo-specific dimers at neutral pH and (2) that the self-association is driven by a high charge complementarity across the contact surface of the proteins. Our theoretical predictions of dimer formation are verified by electrophoretic mobility and N-terminal sequence analysis on bovine lactoferrin. 2010 Elsevier B.V. All rights reserved.

Measuring excess free energies of self-assembled membrane structures.

PubMed

Norizoe, Yuki; Daoulas, Kostas Ch; Müller, Marcus

2010-01-01

Using computer simulation of a solvent-free, coarse-grained model for amphiphilic membranes, we study the excess free energy of hourglass-shaped connections (i.e., stalks) between two apposed bilayer membranes. In order to calculate the free energy by simulation in the canonical ensemble, we reversibly transfer two apposed bilayers into a configuration with a stalk in three steps. First, we gradually replace the intermolecular interactions by an external, ordering field. The latter is chosen such that the structure of the non-interacting system in this field closely resembles the structure of the original, interacting system in the absence of the external field. The absence of structural changes along this path suggests that it is reversible; a fact which is confirmed by expanded-ensemble simulations. Second, the external, ordering field is changed as to transform the non-interacting system from the apposed bilayer structure to two-bilayers connected by a stalk. The final external field is chosen such that the structure of the non-interacting system resembles the structure of the stalk in the interacting system without a field. On the third branch of the transformation path, we reversibly replace the external, ordering field by non-bonded interactions. Using expanded-ensemble techniques, the free energy change along this reversible path can be obtained with an accuracy of 10(-3)k(B)T per molecule in the n VT-ensemble. Calculating the chemical potential, we obtain the free energy of a stalk in the grandcanonical ensemble, and employing semi-grandcanonical techniques, we calculate the change of the excess free energy upon altering the molecular architecture. This computational strategy can be applied to compute the free energy of self-assembled phases in lipid and copolymer systems, and the excess free energy of defects or interfaces.

Molecular Dynamics Simulations of Intrinsically Disordered Proteins: Force Field Evaluation and Comparison with Experiment.

PubMed

Henriques, João; Cragnell, Carolina; Skepö, Marie

2015-07-14

An increasing number of studies using molecular dynamics (MD) simulations of unfolded and intrinsically disordered proteins (IDPs) suggest that current force fields sample conformations that are overly collapsed. Here, we study the applicability of several state-of-the-art MD force fields, of the AMBER and GROMOS variety, for the simulation of Histatin 5, a short (24 residues) cationic salivary IDP with antimicrobial and antifungal properties. The quality of the simulations is assessed in three complementary analyses: (i) protein shape and size comparison with recent experimental small-angle X-ray scattering data; (ii) secondary structure prediction; (iii) energy landscape exploration and conformational class analysis. Our results show that, indeed, standard force fields sample conformations that are too compact, being systematically unable to reproduce experimental evidence such as the scattering function, the shape of the protein as compared with the Kratky plot, and intrapeptide distances obtained through the pair distance distribution function, p(r). The consistency of this deviation suggests that the problem is not mainly due to protein-protein or water-water interactions, whose parametrization varies the most between force fields and water models. In fact, as originally proposed in [ Best et al. J. Chem. Theory Comput. 2014, 10, 5113 - 5124.], balanced protein-water interactions may be the key to solving this problem. Our simulations using this approach produce results in very good agreement with experiment.

Penetration Barrier of Water through Graphynes' Pores: First-Principles Predictions and Force Field Optimization.

PubMed

Bartolomei, Massimiliano; Carmona-Novillo, Estela; Hernández, Marta I; Campos-Martínez, José; Pirani, Fernando; Giorgi, Giacomo; Yamashita, Koichi

2014-02-20

Graphynes are novel two-dimensional carbon-based materials that have been proposed as molecular filters, especially for water purification technologies. We carry out first-principles electronic structure calculations at the MP2C level of theory to assess the interaction between water and graphyne, graphdiyne, and graphtriyne pores. The computed penetration barriers suggest that water transport is unfeasible through graphyne while being unimpeded for graphtriyne. For graphdiyne, with a pore size almost matching that of water, a low barrier is found that in turn disappears if an active hydrogen bond with an additional water molecule on the opposite side of the opening is considered. Thus, in contrast with previous determinations, our results do not exclude graphdiyne as a promising membrane for water filtration. In fact, present calculations lead to water permeation probabilities that are 2 orders of magnitude larger than estimations based on common force fields. A new pair potential for the water-carbon noncovalent component of the interaction is proposed for molecular dynamics simulations involving graphdiyne and water.

Scaling from single molecule to macroscopic adhesion at polymer/metal interfaces.

PubMed

Utzig, Thomas; Raman, Sangeetha; Valtiner, Markus

2015-03-10

Understanding the evolution of macroscopic adhesion based on fundamental molecular interactions is crucial to designing strong and smart polymer/metal interfaces that play an important role in many industrial and biomedical applications. Here we show how macroscopic adhesion can be predicted on the basis of single molecular interactions. In particular, we carry out dynamic single molecule-force spectroscopy (SM-AFM) in the framework of Bell-Evans' theory to gain information about the energy barrier between the bound and unbound states of an amine/gold junction. Furthermore, we use Jarzynski's equality to obtain the equilibrium ground-state energy difference of the amine/gold bond from these nonequilibrium force measurements. In addition, we perform surface forces apparatus (SFA) experiments to measure macroscopic adhesion forces at contacts where approximately 10(7) amine/gold bonds are formed simultaneously. The SFA approach provides an amine/gold interaction energy (normalized by the number of interacting molecules) of (36 ± 1)k(B)T, which is in excellent agreement with the interaction free energy of (35 ± 3)k(B)T calculated using Jarzynski's equality and single-molecule AFM experiments. Our results validate Jarzynski's equality for the field of polymer/metal interactions by measuring both sides of the equation. Furthermore, the comparison of SFA and AFM shows how macroscopic interaction energies can be predicted on the basis of single molecular interactions, providing a new strategy to potentially predict adhesive properties of novel glues or coatings as well as bio- and wet adhesion.

Bacterial-fungal interactions: ecology, mechanisms and challenges.

PubMed

Deveau, Aurélie; Bonito, Gregory; Uehling, Jessie; Paoletti, Mathieu; Becker, Matthias; Bindschedler, Saskia; Hacquard, Stéphane; Hervé, Vincent; Labbé, Jessy; Lastovetsky, Olga A; Mieszkin, Sophie; Millet, Larry J; Vajna, Balázs; Junier, Pilar; Bonfante, Paola; Krom, Bastiaan P; Olsson, Stefan; van Elsas, Jan Dirk; Wick, Lukas Y

2018-05-01

Fungi and bacteria are found living together in a wide variety of environments. Their interactions are significant drivers of many ecosystem functions and are important for the health of plants and animals. A large number of fungal and bacterial families engage in complex interactions that lead to critical behavioural shifts of the microorganisms ranging from mutualism to antagonism. The importance of bacterial-fungal interactions (BFI) in environmental science, medicine and biotechnology has led to the emergence of a dynamic and multidisciplinary research field that combines highly diverse approaches including molecular biology, genomics, geochemistry, chemical and microbial ecology, biophysics and ecological modelling. In this review, we discuss recent advances that underscore the roles of BFI across relevant habitats and ecosystems. A particular focus is placed on the understanding of BFI within complex microbial communities and in regard of the metaorganism concept. We also discuss recent discoveries that clarify the (molecular) mechanisms involved in bacterial-fungal relationships, and the contribution of new technologies to decipher generic principles of BFI in terms of physical associations and molecular dialogues. Finally, we discuss future directions for research in order to stimulate synergy within the BFI research area and to resolve outstanding questions.

Exciton dynamics of C60-based single-photon emitters explored by Hanbury Brown-Twiss scanning tunnelling microscopy.

PubMed

Merino, P; Große, C; Rosławska, A; Kuhnke, K; Kern, K

2015-09-29

Exciton creation and annihilation by charges are crucial processes for technologies relying on charge-exciton-photon conversion. Improvement of organic light sources or dye-sensitized solar cells requires methods to address exciton dynamics at the molecular scale. Near-field techniques have been instrumental for this purpose; however, characterizing exciton recombination with molecular resolution remained a challenge. Here, we study exciton dynamics by using scanning tunnelling microscopy to inject current with sub-molecular precision and Hanbury Brown-Twiss interferometry to measure photon correlations in the far-field electroluminescence. Controlled injection allows us to generate excitons in solid C60 and let them interact with charges during their lifetime. We demonstrate electrically driven single-photon emission from localized structural defects and determine exciton lifetimes in the picosecond range. Monitoring lifetime shortening and luminescence saturation for increasing carrier injection rates provides access to charge-exciton annihilation dynamics. Our approach introduces a unique way to study single quasi-particle dynamics on the ultimate molecular scale.

The Micromechanics of the Moving Contact Line

NASA Technical Reports Server (NTRS)

Han, Minsub; Lichter, Seth; Lin, Chih-Yu; Perng, Yeong-Yan

1996-01-01

The proposed research is divided into three components concerned with molecular structure, molecular orientation, and continuum averages of discrete systems. In the experimental program, we propose exploring how changes in interfacial molecular structure generate contact line motion. Rather than rely on the electrostatic and electrokinetic fields arising from the molecules themselves, we augment their interactions by an imposed field at the solid/liquid interface. By controling the field, we can manipulate the molecular structure at the solid/liquid interface. In response to controlled changes in molecular structure, we observe the resultant contact line motion. In the analytical portion of the proposed research we seek to formulate a system of equations governing fluid motion which accounts for the orientation of fluid molecules. In preliminary work, we have focused on describing how molecular orientation affects the forces generated at the moving contact line. Ideally, as assumed above, the discrete behavior of molecules can be averaged into a continuum theory. In the numerical portion of the proposed research, we inquire whether the contact line region is, in fact, large enough to possess a well-defined average. Additionally, we ask what types of behavior distinguish discrete systems from continuum systems. Might the smallness of the contact line region, in itself, lead to behavior different from that in the bulk? Taken together, our proposed research seeks to identify and accurately account for some of the molecular dynamics of the moving contact line, and attempts to formulate a description from which one can compute the forces at the moving contact line.

A new force field including charge directionality for TMAO in aqueous solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Usui, Kota; Nagata, Yuki, E-mail: sulpizi@uni-mainz.de, E-mail: nagata@mpip-mainz.mpg.de; Hunger, Johannes

We propose a new force field for trimethylamine N-oxide (TMAO), which is designed to reproduce the long-lived and highly directional hydrogen bond between the TMAO oxygen (O{sub TMAO}) atom and surrounding water molecules. Based on the data obtained by ab initio molecular dynamics simulations, we introduce three dummy sites around O{sub TMAO} to mimic the O{sub TMAO} lone pairs and we migrate the negative charge on the O{sub TMAO} to the dummy sites. The force field model developed here improves both structural and dynamical properties of aqueous TMAO solutions. Moreover, it reproduces the experimentally observed dependence of viscosity upon increasingmore » TMAO concentration quantitatively. The simple procedure of the force field construction makes it easy to implement in molecular dynamics simulation packages and makes it compatible with the existing biomolecular force fields. This paves the path for further investigation of protein-TMAO interaction in aqueous solutions.« less

Guided molecular self-assembly: a review of recent efforts

NASA Astrophysics Data System (ADS)

Huie, Jiyun C.

2003-04-01

This paper serves as an introductory review of significant and novel successes achieved in the fields of nanotechnology, particularly in the formation of nanostructures using guided molecular self-assembly methods. Self-assembly is a spontaneous process by which molecules and nanophase entities may materialize into organized aggregates or networks. Through various interactive mechanisms of self-assembly, such as electrostatics, chemistry, surface properties, and via other mediating agents, the technique proves indispensable to recent functional materials and device realizations. The discussion will extend to spontaneous and Langmuir-Blodgett formation of self-assembled monolayers on various substrates, and a number of different categories of self-assembly techniques based on the type of interaction exploited. Combinatorial techniques, known as soft lithography, of micro-contact printing and dip-pen nanolithography, which can be effectively used to up-size nanostructured molecular assemblies to submicrometer and micrometer scale patterns, will also be mentioned.

Effect of peptide length on the conjugation to the gold nanoparticle surface: a molecular dynamic study.

PubMed

Ramezani, Fatemeh; Habibi, Mostafa; Rafii-Tabar, Hashem; Amanlou, Massoud

2015-01-29

Gold nanoparticles now command a great deal of attention for medical applications. Despite the importance of nano-bio interfaces, interaction between peptides and proteins with gold surfaces is not still fully understood, especially in a molecular level. In the present study computational simulation of adsorption of 20 amino acids, in three forms of mono-amino acid, homo di-peptide and homo tri-peptide, on the gold nanoparticles was performed by Gromacs using OPLSAA force field. The flexibility, stability, and size effect of the peptides on the gold nanoparticles were studied as well as the molecular structure of them. According to our results, adsorbed homo tri-peptides on the gold surface had more flexibility, more gyration, and the farthest distance from the GNP in comparison with homo di-peptides and mono-amino acids. Our findings provide new insights into the precise control of interactions between amino acids anchored on the GNPs.

Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins.

PubMed

May, Ali; Pool, René; van Dijk, Erik; Bijlard, Jochem; Abeln, Sanne; Heringa, Jaap; Feenstra, K Anton

2014-02-01

To assess whether two proteins will interact under physiological conditions, information on the interaction free energy is needed. Statistical learning techniques and docking methods for predicting protein-protein interactions cannot quantitatively estimate binding free energies. Full atomistic molecular simulation methods do have this potential, but are completely unfeasible for large-scale applications in terms of computational cost required. Here we investigate whether applying coarse-grained (CG) molecular dynamics simulations is a viable alternative for complexes of known structure. We calculate the free energy barrier with respect to the bound state based on molecular dynamics simulations using both a full atomistic and a CG force field for the TCR-pMHC complex and the MP1-p14 scaffolding complex. We find that the free energy barriers from the CG simulations are of similar accuracy as those from the full atomistic ones, while achieving a speedup of >500-fold. We also observe that extensive sampling is extremely important to obtain accurate free energy barriers, which is only within reach for the CG models. Finally, we show that the CG model preserves biological relevance of the interactions: (i) we observe a strong correlation between evolutionary likelihood of mutations and the impact on the free energy barrier with respect to the bound state; and (ii) we confirm the dominant role of the interface core in these interactions. Therefore, our results suggest that CG molecular simulations can realistically be used for the accurate prediction of protein-protein interaction strength. The python analysis framework and data files are available for download at http://www.ibi.vu.nl/downloads/bioinformatics-2013-btt675.tgz.

Improved model of hydrated calcium ion for molecular dynamics simulations using classical biomolecular force fields.

PubMed

Yoo, Jejoong; Wilson, James; Aksimentiev, Aleksei

2016-10-01

Calcium ions (Ca(2+) ) play key roles in various fundamental biological processes such as cell signaling and brain function. Molecular dynamics (MD) simulations have been used to study such interactions, however, the accuracy of the Ca(2+) models provided by the standard MD force fields has not been rigorously tested. Here, we assess the performance of the Ca(2+) models from the most popular classical force fields AMBER and CHARMM by computing the osmotic pressure of model compounds and the free energy of DNA-DNA interactions. In the simulations performed using the two standard models, Ca(2+) ions are seen to form artificial clusters with chloride, acetate, and phosphate species; the osmotic pressure of CaAc2 and CaCl2 solutions is a small fraction of the experimental values for both force fields. Using the standard parameterization of Ca(2+) ions in the simulations of Ca(2+) -mediated DNA-DNA interactions leads to qualitatively wrong outcomes: both AMBER and CHARMM simulations suggest strong inter-DNA attraction whereas, in experiment, DNA molecules repel one another. The artificial attraction of Ca(2+) to DNA phosphate is strong enough to affect the direction of the electric field-driven translocation of DNA through a solid-state nanopore. To address these shortcomings of the standard Ca(2+) model, we introduce a custom model of a hydrated Ca(2+) ion and show that using our model brings the results of the above MD simulations in quantitative agreement with experiment. Our improved model of Ca(2+) can be readily applied to MD simulations of various biomolecular systems, including nucleic acids, proteins and lipid bilayer membranes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 752-763, 2016. © 2016 Wiley Periodicals, Inc.

Electric-field-driven electron-transfer in mixed-valence molecules.

PubMed

Blair, Enrique P; Corcelli, Steven A; Lent, Craig S

2016-07-07

Molecular quantum-dot cellular automata is a computing paradigm in which digital information is encoded by the charge configuration of a mixed-valence molecule. General-purpose computing can be achieved by arranging these compounds on a substrate and exploiting intermolecular Coulombic coupling. The operation of such a device relies on nonequilibrium electron transfer (ET), whereby the time-varying electric field of one molecule induces an ET event in a neighboring molecule. The magnitude of the electric fields can be quite large because of close spatial proximity, and the induced ET rate is a measure of the nonequilibrium response of the molecule. We calculate the electric-field-driven ET rate for a model mixed-valence compound. The mixed-valence molecule is regarded as a two-state electronic system coupled to a molecular vibrational mode, which is, in turn, coupled to a thermal environment. Both the electronic and vibrational degrees-of-freedom are treated quantum mechanically, and the dissipative vibrational-bath interaction is modeled with the Lindblad equation. This approach captures both tunneling and nonadiabatic dynamics. Relationships between microscopic molecular properties and the driven ET rate are explored for two time-dependent applied fields: an abruptly switched field and a linearly ramped field. In both cases, the driven ET rate is only weakly temperature dependent. When the model is applied using parameters appropriate to a specific mixed-valence molecule, diferrocenylacetylene, terahertz-range ET transfer rates are predicted.

Determining polarizable force fields with electrostatic potentials from quantum mechanical linear response theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hao; Yang, Weitao, E-mail: weitao.yang@duke.edu; Department of Physics, Duke University, Durham, North Carolina 27708

We developed a new method to calculate the atomic polarizabilities by fitting to the electrostatic potentials (ESPs) obtained from quantum mechanical (QM) calculations within the linear response theory. This parallels the conventional approach of fitting atomic charges based on electrostatic potentials from the electron density. Our ESP fitting is combined with the induced dipole model under the perturbation of uniform external electric fields of all orientations. QM calculations for the linear response to the external electric fields are used as input, fully consistent with the induced dipole model, which itself is a linear response model. The orientation of the uniformmore » external electric fields is integrated in all directions. The integration of orientation and QM linear response calculations together makes the fitting results independent of the orientations and magnitudes of the uniform external electric fields applied. Another advantage of our method is that QM calculation is only needed once, in contrast to the conventional approach, where many QM calculations are needed for many different applied electric fields. The molecular polarizabilities obtained from our method show comparable accuracy with those from fitting directly to the experimental or theoretical molecular polarizabilities. Since ESP is directly fitted, atomic polarizabilities obtained from our method are expected to reproduce the electrostatic interactions better. Our method was used to calculate both transferable atomic polarizabilities for polarizable molecular mechanics’ force fields and nontransferable molecule-specific atomic polarizabilities.« less

Phosphorus-32 in the Phage Group: radioisotopes as historical tracers of molecular biology

PubMed Central

Creager, Angela N.H.

2009-01-01

The recent historiography of molecular biology features key technologies, instruments and materials, which offer a different view of the field and its turning points than preceding intellectual and institutional histories. Radioisotopes, in this vein, became essential tools in postwar life science research, including molecular biology, and are here analyzed through their use in experiments on bacteriophage. Isotopes were especially well suited for studying the dynamics of chemical transformation over time, through metabolic pathways or life cycles. Scientists labeled phage with phosphorus-32 in order to trace the transfer of genetic material between parent and progeny in virus reproduction. Initial studies of this type did not resolve the mechanism of generational transfer but unexpectedly gave rise to a new style of molecular radiobiology based on the inactivation of phage by the radioactive decay of incorporated phosphorus-32. These ‘suicide experiments’, a preoccupation of phage researchers in the mid-1950s, reveal how molecular biologists interacted with the traditions and practices of radiation geneticists as well as those of biochemists as they were seeking to demarcate a new field. The routine use of radiolabels to visualize nucleic acids emerged as an enduring feature of molecular biological experimentation. PMID:19268872

Short-peptide-based molecular hydrogels: novel gelation strategies and applications for tissue engineering and drug delivery

NASA Astrophysics Data System (ADS)

Wang, Huaimin; Yang, Zhimou

2012-08-01

Molecular hydrogels hold big potential for tissue engineering and controlled drug delivery. Our lab focuses on short-peptide-based molecular hydrogels formed by biocompatible methods and their applications in tissue engineering (especially, 3D cell culture) and controlled drug delivery. This feature article firstly describes our recent progresses of the development of novel methods to form hydrogels, including the strategy of disulfide bond reduction and assistance with specific protein-peptide interactions. We then introduce the applications of our hydrogels in fields of controlled stem cell differentiation, cell culture, surface modifications of polyester materials by molecular self-assembly, and anti-degradation of recombinant complex proteins. A novel molecular hydrogel system of hydrophobic compounds that are only formed by hydrolysis processes was also included in this article. The hydrogels of hydrophobic compounds, especially those of hydrophobic therapeutic agents, may be developed into a carrier-free delivery system for long term delivery of therapeutic agents. With the efforts in this field, we believe that molecular hydrogels formed by short peptides and hydrophobic therapeutic agents can be practically applied for 3D cell culture and long term drug delivery in near future, respectively.

Frequency-dependent local field factors in dielectric liquids by a polarizable force field and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Davari, Nazanin; Haghdani, Shokouh; Åstrand, Per-Olof

2015-12-01

A force field model for calculating local field factors, i.e. the linear response of the local electric field for example at a nucleus in a molecule with respect to an applied electric field, is discussed. It is based on a combined charge-transfer and point-dipole interaction model for the polarizability, and thereby it includes two physically distinct terms for describing electronic polarization: changes in atomic charges arising from transfer of charge between the atoms and atomic induced dipole moments. A time dependence is included both for the atomic charges and the atomic dipole moments and if they are assumed to oscillate with the same frequency as the applied electric field, a model for frequency-dependent properties are obtained. Furthermore, if a life-time of excited states are included, a model for the complex frequency-dependent polariability is obtained including also information about excited states and the absorption spectrum. We thus present a model for the frequency-dependent local field factors through the first molecular excitation energy. It is combined with molecular dynamics simulations of liquids where a large set of configurations are sampled and for which local field factors are calculated. We are normally not interested in the average of the local field factor but rather in configurations where it is as high as possible. In electrical insulation, we would like to avoid high local field factors to reduce the risk for electrical breakdown, whereas for example in surface-enhanced Raman spectroscopy, high local field factors are desired to give dramatically increased intensities.

Enhancement of magnetic anisotropy in a Mn-Bi heterobimetallic complex.

PubMed

Pearson, Tyler J; Fataftah, Majed S; Freedman, Danna E

2016-09-15

A novel Mn 2+ Bi 3+ heterobimetallic complex, featuring the closest MnBi interaction for a paramagnetic molecular species, exhibits unusually large axial zero-field splitting. We attribute this enhancement to the proximity of Mn 2+ to a heavy main group element, namely, bismuth.

High-field EPR on membrane proteins - crossing the gap to NMR.

PubMed

Möbius, Klaus; Lubitz, Wolfgang; Savitsky, Anton

2013-11-01

In this review on advanced EPR spectroscopy, which addresses both the EPR and NMR communities, considerable emphasis is put on delineating the complementarity of NMR and EPR concerning the measurement of molecular interactions in large biomolecules. From these interactions, detailed information can be revealed on structure and dynamics of macromolecules embedded in solution- or solid-state environments. New developments in pulsed microwave and sweepable cryomagnet technology as well as ultrafast electronics for signal data handling and processing have pushed to new horizons the limits of EPR spectroscopy and its multifrequency extensions concerning the sensitivity of detection, the selectivity with respect to interactions, and the resolution in frequency and time domains. One of the most important advances has been the extension of EPR to high magnetic fields and microwave frequencies, very much in analogy to what happens in NMR. This is exemplified by referring to ongoing efforts for signal enhancement in both NMR and EPR double-resonance techniques by exploiting dynamic nuclear or electron spin polarization via unpaired electron spins and their electron-nuclear or electron-electron interactions. Signal and resolution enhancements are particularly spectacular for double-resonance techniques such as ENDOR and PELDOR at high magnetic fields. They provide greatly improved orientational selection for disordered samples that approaches single-crystal resolution at canonical g-tensor orientations - even for molecules with small g-anisotropies. Exchange of experience between the EPR and NMR communities allows for handling polarization and resolution improvement strategies in an optimal manner. Consequently, a dramatic improvement of EPR detection sensitivity could be achieved, even for short-lived paramagnetic reaction intermediates. Unique structural and dynamic information is thus revealed that can hardly be obtained by any other analytical techniques. Micromolar quantities of sample molecules have become sufficient to characterize stable and transient reaction intermediates of complex molecular systems - offering highly interesting applications for chemists, biochemists and molecular biologists. In three case studies, representative examples of advanced EPR spectroscopy are reviewed: (I) High-field PELDOR and ENDOR structure determination of cation-anion radical pairs in reaction centers from photosynthetic purple bacteria and cyanobacteria (Photosystem I); (II) High-field ENDOR and ELDOR-detected NMR spectroscopy on the oxygen-evolving complex of Photosystem II; and (III) High-field electron dipolar spectroscopy on nitroxide spin-labelled bacteriorhodopsin for structure-function studies. An extended conclusion with an outlook to further developments and applications is also presented. Copyright © 2013 Elsevier B.V. All rights reserved.

Toward optimized potential functions for protein-protein interactions in aqueous solutions: osmotic second virial coefficient calculations using the MARTINI coarse-grained force field

PubMed Central

Stark, Austin C.; Andrews, Casey T.

2013-01-01

Coarse-grained (CG) simulation methods are now widely used to model the structure and dynamics of large biomolecular systems. One important issue for using such methods – especially with regard to using them to model, for example, intracellular environments – is to demonstrate that they can reproduce experimental data on the thermodynamics of protein-protein interactions in aqueous solutions. To examine this issue, we describe here simulations performed using the popular coarse-grained MARTINI force field, aimed at computing the thermodynamics of lysozyme and chymotrypsinogen self-interactions in aqueous solution. Using molecular dynamics simulations to compute potentials of mean force between a pair of protein molecules, we show that the original parameterization of the MARTINI force field is likely to significantly overestimate the strength of protein-protein interactions to the extent that the computed osmotic second virial coefficients are orders of magnitude more negative than experimental estimates. We then show that a simple down-scaling of the van der Waals parameters that describe the interactions between protein pseudo-atoms can bring the simulated thermodynamics into much closer agreement with experiment. Overall, the work shows that it is feasible to test explicit-solvent CG force fields directly against thermodynamic data for proteins in aqueous solutions, and highlights the potential usefulness of osmotic second virial coefficient measurements for fully parameterizing such force fields. PMID:24223529

Toward optimized potential functions for protein-protein interactions in aqueous solutions: osmotic second virial coefficient calculations using the MARTINI coarse-grained force field.

PubMed

Stark, Austin C; Andrews, Casey T; Elcock, Adrian H

2013-09-10

Coarse-grained (CG) simulation methods are now widely used to model the structure and dynamics of large biomolecular systems. One important issue for using such methods - especially with regard to using them to model, for example, intracellular environments - is to demonstrate that they can reproduce experimental data on the thermodynamics of protein-protein interactions in aqueous solutions. To examine this issue, we describe here simulations performed using the popular coarse-grained MARTINI force field, aimed at computing the thermodynamics of lysozyme and chymotrypsinogen self-interactions in aqueous solution. Using molecular dynamics simulations to compute potentials of mean force between a pair of protein molecules, we show that the original parameterization of the MARTINI force field is likely to significantly overestimate the strength of protein-protein interactions to the extent that the computed osmotic second virial coefficients are orders of magnitude more negative than experimental estimates. We then show that a simple down-scaling of the van der Waals parameters that describe the interactions between protein pseudo-atoms can bring the simulated thermodynamics into much closer agreement with experiment. Overall, the work shows that it is feasible to test explicit-solvent CG force fields directly against thermodynamic data for proteins in aqueous solutions, and highlights the potential usefulness of osmotic second virial coefficient measurements for fully parameterizing such force fields.

The Emerging Field of Human Social Genomics

PubMed Central

Slavich, George M.; Cole, Steven W.

2013-01-01

Although we generally experience our bodies as being biologically stable across time and situations, an emerging field of research is demonstrating that external social conditions, especially our subjective perceptions of those conditions, can influence our most basic internal biological processes—namely, the expression of our genes. This research on human social genomics has begun to identify the types of genes that are subject to social-environmental regulation, the neural and molecular mechanisms that mediate the effects of social processes on gene expression, and the genetic polymorphisms that moderate individual differences in genomic sensitivity to social context. The molecular models resulting from this research provide new opportunities for understanding how social and genetic factors interact to shape complex behavioral phenotypes and susceptibility to disease. This research also sheds new light on the evolution of the human genome and challenges the fundamental belief that our molecular makeup is relatively stable and impermeable to social-environmental influence. PMID:23853742

Molecular Docking, Molecular Dynamics, and Structure–Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists

PubMed Central

2017-01-01

Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure–activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3–7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design. PMID:28125215

Molecular Docking, Molecular Dynamics, and Structure-Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists.

PubMed

Noha, Stefan M; Schmidhammer, Helmut; Spetea, Mariana

2017-06-21

Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure-activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3-7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design.

Spin-interaction effects for ultralong-range Rydberg molecules in a magnetic field

NASA Astrophysics Data System (ADS)

Hummel, Frederic; Fey, Christian; Schmelcher, Peter

2018-04-01

We investigate the fine and spin structure of ultralong-range Rydberg molecules exposed to a homogeneous magnetic field. Each molecule consists of a 87Rb Rydberg atom the outer electron of which interacts via spin-dependent s - and p -wave scattering with a polarizable 87Rb ground-state atom. Our model includes also the hyperfine structure of the ground-state atom as well as spin-orbit couplings of the Rydberg and ground-state atom. We focus on d -Rydberg states and principal quantum numbers n in the vicinity of 40. The electronic structure and vibrational states are determined in the framework of the Born-Oppenheimer approximation for varying field strengths ranging from a few up to hundred Gauss. The results show that the interplay between the scattering interactions and the spin couplings gives rise to a large variety of molecular states in different spin configurations as well as in different spatial arrangements that can be tuned by the magnetic field. This includes relatively regularly shaped energy surfaces in a regime where the Zeeman splitting is large compared to the scattering interaction but small compared to the Rydberg fine structure, as well as more complex structures for both weaker and stronger fields. We quantify the impact of spin couplings by comparing the extended theory to a spin-independent model.

Dissolution study of active pharmaceutical ingredients using molecular dynamics simulations with classical force fields

NASA Astrophysics Data System (ADS)

Greiner, Maximilian; Elts, Ekaterina; Schneider, Julian; Reuter, Karsten; Briesen, Heiko

2014-11-01

The CHARMM, general Amber and OPLS force fields are evaluated for their suitability in simulating the molecular dynamics of the dissolution of the hydrophobic, small-molecule active pharmaceutical ingredients aspirin, ibuprofen, and paracetamol in aqueous media. The force fields are evaluated by comparison with quantum chemical simulations or experimental references on the basis of the following capabilities: accurately representing intra- and intermolecular interactions, appropriately reproducing crystal lattice parameters, adequately describing thermodynamic properties, and the qualitative description of the dissolution behavior. To make this approach easily accessible for evaluating the dissolution properties of novel drug candidates in the early stage of drug development, the force field parameter files are generated using online resources such as the SWISS PARAM servers, and the software packages ACPYPE and Maestro. All force fields are found to reproduce the intermolecular interactions with a reasonable degree of accuracy, with the general Amber and CHARMM force fields showing the best agreement with quantum mechanical calculations. A stable crystal bulk structure is obtained for all model substances, except for ibuprofen, where the reproductions of the lattice parameters and observed crystal stability are considerably poor for all force fields. The heat of solution used to evaluate the solid-to-solution phase transitions is found to be in qualitative agreement with the experimental data for all combinations tested, with the results being quantitatively optimum for the general Amber and CHARMM force fields. For aspirin and paracetamol, stable crystal-water interfaces were obtained. The (100), (110), (011) and (001) interfaces of aspirin or paracetamol and water were simulated for each force field for 30 ns. Although generally expected as a rare event, in some of the simulations, dissolution is observed at 310 K and ambient pressure conditions.

Interaction between benzenedithiolate and gold: Classical force field for chemical bonding

NASA Astrophysics Data System (ADS)

Leng, Yongsheng; Krstić, Predrag S.; Wells, Jack C.; Cummings, Peter T.; Dean, David J.

2005-06-01

We have constructed a group of classical potentials based on ab initio density-functional theory (DFT) calculations to describe the chemical bonding between benzenedithiolate (BDT) molecule and gold atoms, including bond stretching, bond angle bending, and dihedral angle torsion involved at the interface between the molecule and gold clusters. Three DFT functionals, local-density approximation (LDA), PBE0, and X3LYP, have been implemented to calculate single point energies (SPE) for a large number of molecular configurations of BDT-1, 2 Au complexes. The three DFT methods yield similar bonding curves. The variations of atomic charges from Mulliken population analysis within the molecule/metal complex versus different molecular configurations have been investigated in detail. We found that, except for bonded atoms in BDT-1, 2 Au complexes, the Mulliken partial charges of other atoms in BDT are quite stable, which significantly reduces the uncertainty in partial charge selections in classical molecular simulations. Molecular-dynamics (MD) simulations are performed to investigate the structure of BDT self-assembled monolayer (SAM) and the adsorption geometry of S adatoms on Au (111) surface. We found that the bond-stretching potential is the most dominant part in chemical bonding. Whereas the local bonding geometry of BDT molecular configuration may depend on the DFT functional used, the global packing structure of BDT SAM is quite independent of DFT functional, even though the uncertainty of some force-field parameters for chemical bonding can be as large as ˜100%. This indicates that the intermolecular interactions play a dominant role in determining the BDT SAMs global packing structure.

Interaction between benzenedithiolate and gold: classical force field for chemical bonding.

PubMed

Leng, Yongsheng; Krstić, Predrag S; Wells, Jack C; Cummings, Peter T; Dean, David J

2005-06-22

We have constructed a group of classical potentials based on ab initio density-functional theory (DFT) calculations to describe the chemical bonding between benzenedithiolate (BDT) molecule and gold atoms, including bond stretching, bond angle bending, and dihedral angle torsion involved at the interface between the molecule and gold clusters. Three DFT functionals, local-density approximation (LDA), PBE0, and X3LYP, have been implemented to calculate single point energies (SPE) for a large number of molecular configurations of BDT-1, 2 Au complexes. The three DFT methods yield similar bonding curves. The variations of atomic charges from Mulliken population analysis within the molecule/metal complex versus different molecular configurations have been investigated in detail. We found that, except for bonded atoms in BDT-1, 2 Au complexes, the Mulliken partial charges of other atoms in BDT are quite stable, which significantly reduces the uncertainty in partial charge selections in classical molecular simulations. Molecular-dynamics (MD) simulations are performed to investigate the structure of BDT self-assembled monolayer (SAM) and the adsorption geometry of S adatoms on Au (111) surface. We found that the bond-stretching potential is the most dominant part in chemical bonding. Whereas the local bonding geometry of BDT molecular configuration may depend on the DFT functional used, the global packing structure of BDT SAM is quite independent of DFT functional, even though the uncertainty of some force-field parameters for chemical bonding can be as large as approximately 100%. This indicates that the intermolecular interactions play a dominant role in determining the BDT SAMs global packing structure.

Statistical field theory description of inhomogeneous polarizable soft matter

NASA Astrophysics Data System (ADS)

Martin, Jonathan M.; Li, Wei; Delaney, Kris T.; Fredrickson, Glenn H.

2016-10-01

We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

Statistical field theory description of inhomogeneous polarizable soft matter.

PubMed

Martin, Jonathan M; Li, Wei; Delaney, Kris T; Fredrickson, Glenn H

2016-10-21

We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

Elucidating sequence and solvent specific design targets to protect and stabilize enzymes for biocatalysis in ionic liquids.

PubMed

Sprenger, K G; Plaks, J G; Kaar, J L; Pfaendtner, J

2017-07-05

For many different frameworks, the structure, function, and dynamics of an enzyme is largely determined by the nature of its interactions with the surrounding host environment, thus a molecular level understanding of enzyme/host interactions is essential to the design of new processes and applications. Ionic liquid (IL) solvents are a popular class of solvents in which to study enzyme behavior, yet it is still not possible to predict how a given enzyme will behave in a given IL solvent. Furthermore, a dearth of experimental data with which to evaluate simulation force fields has prevented the full integration of experimental and computational techniques to gain a complete picture of enzyme/IL interactions. Utilizing recently published crystallographic data of an enzyme in complex with an IL, this study aims to validate the use of current molecular force fields for studying enzyme/IL interactions, and to provide new mechanistic insight into enzyme stabilization in IL solvents. Classical molecular dynamics (MD) simulations have been performed on both the folded and unfolded state of Bacillus subtilis lipase A and a quadruple-mutant version of lipase A, in solutions of aqueous 1-butyl-3-methylimidazolium chloride. Results show classical MD simulations can predict the preferred surface binding locations of IL cations as well as reductions in IL anion binding to mutated surface residues with high accuracy. The results also point to a mechanistic difference between IL binding to the folded and unfolded state of an enzyme, which we call the "counter-ion effect". These findings could have important implications for future rational design efforts to stabilize enzymes in non-conventional media.

Insights into plant plasma membrane aquaporin trafficking.

PubMed

Hachez, Charles; Besserer, Arnaud; Chevalier, Adrien S; Chaumont, François

2013-06-01

Plasma membrane intrinsic proteins (PIPs) are plant aquaporins that facilitate the diffusion of water and small uncharged solutes through the cell membrane. Deciphering the network of interacting proteins that modulate PIP trafficking to and activity in the plasma membrane is essential to improve our knowledge about PIP regulation and function. This review highlights the most recent advances related to PIP subcellular routing and dynamic redistribution, identifies some key molecular interacting proteins, and indicates exciting directions for future research in this field. A better understanding of the mechanisms by which plants optimize water movement might help in identifying new molecular players of agronomical relevance involved in the control of cellular water uptake and drought tolerance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Free energy calculation of permeant-membrane interactions using molecular dynamics simulations.

PubMed

Elvati, Paolo; Violi, Angela

2012-01-01

Nanotoxicology, the science concerned with the safe use of nanotechnology and nanostructure design for biological applications, is a field of research that has recently received great attention, as a result of the rapid growth in nanotechnology. Many nanostructures are of a scale and chemical composition similar to many biomolecular environments, and recent papers have reported evident toxicity of selected nanoparticles. Molecular simulations can help develop a mechanistic understanding of how structural properties affect bioactivity. In this chapter, we describe how to compute the free energy of interactions between cellular membranes and benzene, the main constituent of some toxic carbonaceous particles, with well-tempered metadynamics. This algorithm reconstructs the free energy surface and accelerates rare events in a coarse-grained representation of the system.

Molecular simulations bring new insights into flavonoid/quercetinase interaction modes.

PubMed

Fiorucci, Sébastien; Golebiowski, Jérôme; Cabrol-Bass, Daniel; Antonczak, Serge

2007-06-01

Molecular dynamics simulations, using the AMBER force field, were performed to study Quercetin 2,3-Dioxygenase enzyme (Quercetinase or 2,3QD). We have analyzed the structural modifications of the active site and of the linker region between the native enzyme and the enzyme-substrate complex. New structural informations, such as an allosteric effect in the presence of the substrate, as well as description of the enzyme-substrate interactions and values of binding free energies were brought out. All these results confirm the idea that the linker encloses the substrate in the active site and also enlighten the recognition role of the substrate B-ring by the enzyme. Moreover, a specific interaction scheme has been proposed to explain the relative degradation rate of various flavonoid compounds under the oxygenolysis reaction catalyzed by the Quercetin 2,3-Dioxygenase enzyme. 2007 Wiley-Liss, Inc.

The merger of electrochemistry and molecular electronics.

PubMed

McCreery, Richard L

2012-02-01

Molecular Electronics has the potential to greatly enhance existing silicon-based microelectronics to realize new functions, higher device density, lower power consumption, and lower cost. Although the investigation of electron transport through single molecules and molecular monolayers in "molecular junctions" is a recent development, many of the relevant concepts and phenomena are derived from electrochemistry, as practiced for the past several decades. The past 10+ years have seen an explosion of research activity directed toward how the structure of molecules affects electron transport in molecular junctions, with the ultimate objective of "rational design" of molecular components with new electronic functions, such as chemical sensing, interactions with light, and low-cost, low-power consumer electronics. In order to achieve these scientifically and commercially important objectives, the factors controlling charge transport in molecules "connected" to conducting contacts must be understood, and methods for massively parallel manufacturing of molecular circuits must be developed. This Personal Account describes the development of reproducible and robust molecular electronic devices, starting with modified electrodes used in electrochemistry and progressing to manufacturable molecular junctions. Although the field faced some early difficulties in reliability and characterization, the pieces are now in place for rapid advances in understanding charge transport at the molecular level. Inherent in the field of Molecular Electronics are many electrochemical concepts, including tunneling, redox exchange, activated electron transfer, and electron coupling between molecules and conducting contacts. Copyright © 2012 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.

EDITORIAL: 18th European Conference on Dynamics of Molecular Systems 18th European Conference on Dynamics of Molecular Systems

NASA Astrophysics Data System (ADS)

Varandas, A. J. C.

2011-08-01

This special section of Comments on Atomic, Molecular and Optical Physics (CAMOP) in Physica Scripta collects some of the papers that have been presented at the 18th European Conference on Dynamics of Molecular Systems MOLEC 2010 held in September 2010 in Curia, Portugal, as part of a series of biennial MOLEC conferences. This started in 1976 in Trento, Italy, and has continued, visiting 17 cities in 11 countries, namely Denmark, The Netherlands, Israel, France, Italy, Germany, Czech Republic, Spain, United Kingdom, Turkey and Russia. Following the MOLEC tradition, the scientific programme of the Curia meeting focused on experimental and theoretical studies of molecular interactions, collision dynamics, spectroscopy, and related fields. It included invited speakers from 22 countries, who were asked to summarize the problems reported in their presentations with the objective of revealing the current thinking of leading researchers in atomic, molecular and optical physics. It is hoped that their authoritative contributions presented in this CAMOP special section will also appeal to non-specialists through their clear and broad introductions to the field as well as references to the accessible literature. This CAMOP special section comprises ten contributions, which cover theoretical studies on the electronic structure of molecules and clusters as well as dynamics of elastic, inelastic and reactive encounters between atoms, molecules, ions, clusters and surfaces. Specifically, it includes electronic structure calculations using the traditional coupled-cluster method (Barreto et al 028111), the electron-attached equation-of-motion coupled cluster method (Hansen et al 028110), the diffusion Monte Carlo method (López-Durán et al 028107) and the path-integral Monte Carlo method (Barragán et al 028109). The contributions on molecular dynamics include on-the-fly quasi-classical trajectories on a five-atom molecule (Yu 028104), quantum reaction dynamics on triatomics (Bovino et al 028103, and Hankel et al 028102) and statistical reaction dynamics using a model based on the long-range interaction potential (McCarroll 028106). A contribution on gas-surface interactions is also included (Sahoo et al 028105) as well as first-principles ab initio calculations to explore the hydrogen-graphene interaction (Irving et al 028108). These articles reflect the recent progress made in this field and constructively build on work described in the previous three MOLEC special sections of CAMOP published in Physica Scripta. I thank, on behalf of the scientific organizing committee of MOLEC, all the authors who contributed and Physica Scripta for providing a platform for the publication of this special section dedicated to MOLEC 2010. A special thanks goes to the CAMOP Editor, Harold Linarz, for the excellent guidance in handling the editorial work. I hope that the articles catalyze the attention of the readers towards the topics covered and contribute in attracting them to attend MOLEC 2012 in Oxford, UK.

Density functional theory based study of molecular interactions, recognition, engineering, and quantum transport in π molecular systems.

PubMed

Cho, Yeonchoo; Cho, Woo Jong; Youn, Il Seung; Lee, Geunsik; Singh, N Jiten; Kim, Kwang S

2014-11-18

CONSPECTUS: In chemical and biological systems, various interactions that govern the chemical and physical properties of molecules, assembling phenomena, and electronic transport properties compete and control the microscopic structure of materials. The well-controlled manipulation of each component can allow researchers to design receptors or sensors, new molecular architectures, structures with novel morphology, and functional molecules or devices. In this Account, we describe the structures and electronic and spintronic properties of π-molecular systems that are important for controlling the architecture of a variety of carbon-based systems. Although DFT is an important tool for describing molecular interactions, the inability of DFT to accurately represent dispersion interactions has made it difficult to properly describe π-interactions. However, the recently developed dispersion corrections for DFT have allowed us to include these dispersion interactions cost-effectively. We have investigated noncovalent interactions of various π-systems including aromatic-π, aliphatic-π, and non-π systems based on dispersion-corrected DFT (DFT-D). In addition, we have addressed the validity of DFT-D compared with the complete basis set (CBS) limit values of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)] and Møller-Plesset second order perturbation theory (MP2). The DFT-D methods are still unable to predict the correct ordering in binding energies within the benzene dimer and the cyclohexane dimer. Nevertheless, the overall DFT-D predicted binding energies are in reasonable agreement with the CCSD(T) results. In most cases, results using the B97-D3 method closely reproduce the CCSD(T) results with the optimized energy-fitting parameters. On the other hand, vdW-DF2 and PBE0-TS methods estimate the dispersion energies from the calculated electron density. In these approximations, the interaction energies around the equilibrium point are reasonably close to the CCSD(T) results but sometimes slightly deviate from them because interaction energies were not particularly optimized with parameters. Nevertheless, because the electron cloud deforms when neighboring atoms/ions induce an electric field, both vdW-DF2 and PBE0-TS seem to properly reproduce the resulting change of dispersion interaction. Thus, improvements are needed in both vdW-DF2 and PBE0-TS to better describe the interaction energies, while the B97-D3 method could benefit from the incorporation of polarization-driven energy changes that show highly anisotropic behavior. Although the current DFT-D methods need further improvement, DFT-D is very useful for computer-aided molecular design. We have used these newly developed DFT-D methods to calculate the interactions between graphene and DNA nucleobases. Using DFT-D, we describe the design of molecular receptors of π-systems, graphene based electronic devices, metalloporphyrin half-metal based spintronic devices as graphene nanoribbon (GNR) analogs, and graphene based molecular electronic devices for DNA sequencing. DFT-D has also helped us understand quantum phenomena in materials and devices of π-systems including graphene.

Universal dissymmetry and the origin of biomolecular chirality.

PubMed

Mason, S F

1987-01-01

Handed systems are distributed over four general domains. These span the fundamental particles, the molecular enantiomers, the crystal enantiomorphs, and the spiral galaxies. The characterisation of the molecular enantiomers followed from the identification of the crystal enantiomorphs and revealed a chiral homogeneity in the biomolecules of the organic world. The origin of the homogeneity has been variously ascribed to a universal dissymmetric force, from Pasteur, or to a chance choice of the initial enantiomer perpetuated by the stereoselection of diastereomer production with recycling, from Fischer's "key and lock" hypothesis. The classical chiral fields identified by Curie require a particular time or location on the Earth's surface for a determinate molecular enantioselection, as do the weak charged current agencies of the non-classical weak interaction. The weak neutral current of the electroweak interaction provides a constant and uniform chiral agency which favours both the L-series of amino acids and polypeptides and the parent aldotriose of the D-series of sugars. The enantiomeric bias of the electroweak interaction is small at the molecular level: it may become significant either as a trigger-perturbation guiding the transition from a metastable autocatalytic racemic process to one of the two constituent enantiomeric reaction channels, or by cumulative amplification in a large chirally-homogeneous aggregate of enantiomer units.

Single molecular orientation switching of an endohedral metallofullerene.

PubMed

Yasutake, Yuhsuke; Shi, Zujin; Okazaki, Toshiya; Shinohara, Hisanori; Majima, Yutaka

2005-06-01

The single molecular orientation switching of the Tb@C82 endohedral metallofullerene has been studied by using low-temperature ultrahigh vacuum (UHV) scanning tunneling microscopy (STM). An octanethiol self-assembled monolayer (SAM) was introduced between Tb@C82 and the Au111 substrate to control the thermal rotational states of Tb@C82. Scanning tunneling spectroscopy (STS) of Tb@C82 on an octanethiol SAM at 13 K demonstrated hysteresis including negative differential conductance (NDC). This observed hysteresis and NDC is interpreted in terms of a switching of the Tb@C82 molecular orientation caused by the interaction between its electric dipole moment and an external electric field.

Molecular dynamics simulations of field emission from a planar nanodiode

NASA Astrophysics Data System (ADS)

Torfason, Kristinn; Valfells, Agust; Manolescu, Andrei

2015-03-01

High resolution molecular dynamics simulations with full Coulomb interactions of electrons are used to investigate field emission in planar nanodiodes. The effects of space-charge and emitter radius are examined and compared to previous results concerning transition from Fowler-Nordheim to Child-Langmuir current [Y. Y. Lau, Y. Liu, and R. K. Parker, Phys. Plasmas 1, 2082 (1994) and Y. Feng and J. P. Verboncoeur, Phys. Plasmas 13, 073105 (2006)]. The Fowler-Nordheim law is used to determine the current density injected into the system and the Metropolis-Hastings algorithm to find a favourable point of emission on the emitter surface. A simple fluid like model is also developed and its results are in qualitative agreement with the simulations.

Molecular dynamics simulations of field emission from a planar nanodiode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torfason, Kristinn; Valfells, Agust; Manolescu, Andrei

High resolution molecular dynamics simulations with full Coulomb interactions of electrons are used to investigate field emission in planar nanodiodes. The effects of space-charge and emitter radius are examined and compared to previous results concerning transition from Fowler-Nordheim to Child-Langmuir current [Y. Y. Lau, Y. Liu, and R. K. Parker, Phys. Plasmas 1, 2082 (1994) and Y. Feng and J. P. Verboncoeur, Phys. Plasmas 13, 073105 (2006)]. The Fowler-Nordheim law is used to determine the current density injected into the system and the Metropolis-Hastings algorithm to find a favourable point of emission on the emitter surface. A simple fluid likemore » model is also developed and its results are in qualitative agreement with the simulations.« less

An approach to spin-resolved molecular gas microscopy

NASA Astrophysics Data System (ADS)

Covey, Jacob P.; De Marco, Luigi; Acevedo, Óscar L.; Rey, Ana Maria; Ye, Jun

2018-04-01

Ultracold polar molecules are an ideal platform for studying many-body physics with long-range dipolar interactions. Experiments in this field have progressed enormously, and several groups are pursuing advanced apparatus for manipulation of molecules with electric fields as well as single-atom-resolved in situ detection. Such detection has become ubiquitous for atoms in optical lattices and tweezer arrays, but has yet to be demonstrated for ultracold polar molecules. Here we present a proposal for the implementation of site-resolved microscopy for polar molecules, and specifically discuss a technique for spin-resolved molecular detection. We use numerical simulation of spin dynamics of lattice-confined polar molecules to show how such a scheme would be of utility in a spin-diffusion experiment.

PDZ binding to the BAR domain of PICK1 is elucidated by coarse-grained molecular dynamics.

PubMed

He, Yi; Liwo, Adam; Weinstein, Harel; Scheraga, Harold A

2011-01-07

A key regulator of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor traffic, PICK1 is known to interact with over 40 other proteins, including receptors, transporters and ionic channels, and to be active mostly as a homodimer. The current lack of a complete PICK1 structure determined at atomic resolution hinders the elucidation of its functional mechanisms. Here, we identify interactions between the component PDZ and BAR domains of PICK1 by calculating possible binding sites for the PDZ domain of PICK1 (PICK1-PDZ) to the homology-modeled, crescent-shaped dimer of the PICK1-BAR domain using multiplexed replica-exchange molecular dynamics (MREMD) and canonical molecular dynamics simulations with the coarse-grained UNRES force field. The MREMD results show that the preferred binding site for the single PDZ domain is the concave cavity of the BAR dimer. A second possible binding site is near the N-terminus of the BAR domain that is linked directly to the PDZ domain. Subsequent short canonical molecular dynamics simulations used to determine how the PICK1-PDZ domain moves to the preferred binding site on the BAR domain of PICK1 revealed that initial hydrophobic interactions drive the progress of the simulated binding. Thus, the concave face of the BAR dimer accommodates the PDZ domain first by weak hydrophobic interactions and then the PDZ domain slides to the center of the concave face, where more favorable hydrophobic interactions take over. Copyright © 2010 Elsevier Ltd. All rights reserved.

Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

PubMed Central

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L.; Nishihara, Reiko; Tan, Andy S.; Kawachi, Ichiro; Ogino, Shuji

2015-01-01

Summary The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations, and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial, and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors, and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference, and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology, and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors, and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging, and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

Integration of molecular pathology, epidemiology and social science for global precision medicine.

PubMed

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

2016-01-01

The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

The evaluation and validation of copper (II) force field parameters of the Auxiliary Activity family 9 enzymes

NASA Astrophysics Data System (ADS)

Moses, Vuyani; Tastan Bishop, Özlem; Lobb, Kevin A.

2017-06-01

The Auxiliary Activity family 9 (AA9) proteins are Cu2+ coordinating enzymes which are crucial for the early stages of cellulose degradation. In this study, the force field parameters for copper-containing bonds in the Type 1 AA9 protein active site were established and used in a molecular dynamics simulation on a solvated, neutralized system containing an AA9 protein, Cu2+ and a β-cellulose surface. The copper to cellulose interaction was evident during the dynamics, which could also be accelerated by the use of high Cusbnd O van der Waals parameters. The interaction of AA9, Cu2+ and cellulose is described in detail.

Free energies of binding from large-scale first-principles quantum mechanical calculations: application to ligand hydration energies.

PubMed

Fox, Stephen J; Pittock, Chris; Tautermann, Christofer S; Fox, Thomas; Christ, Clara; Malcolm, N O J; Essex, Jonathan W; Skylaris, Chris-Kriton

2013-08-15

Schemes of increasing sophistication for obtaining free energies of binding have been developed over the years, where configurational sampling is used to include the all-important entropic contributions to the free energies. However, the quality of the results will also depend on the accuracy with which the intermolecular interactions are computed at each molecular configuration. In this context, the energy change associated with the rearrangement of electrons (electronic polarization and charge transfer) upon binding is a very important effect. Classical molecular mechanics force fields do not take this effect into account explicitly, and polarizable force fields and semiempirical quantum or hybrid quantum-classical (QM/MM) calculations are increasingly employed (at higher computational cost) to compute intermolecular interactions in free-energy schemes. In this work, we investigate the use of large-scale quantum mechanical calculations from first-principles as a way of fully taking into account electronic effects in free-energy calculations. We employ a one-step free-energy perturbation (FEP) scheme from a molecular mechanical (MM) potential to a quantum mechanical (QM) potential as a correction to thermodynamic integration calculations within the MM potential. We use this approach to calculate relative free energies of hydration of small aromatic molecules. Our quantum calculations are performed on multiple configurations from classical molecular dynamics simulations. The quantum energy of each configuration is obtained from density functional theory calculations with a near-complete psinc basis set on over 600 atoms using the ONETEP program.

Biomolecular dynamics and binding studies in the living cell.

PubMed

Diekmann, Stephan; Hoischen, Christian

2014-03-01

Isolation and preparation of proteins of higher organisms often is a tedious task. In the case of success, the properties of these proteins and their interactions with other proteins can be studied in vitro. If however, these proteins are modified in the cell in order to gain or change function, this is non-trivial to correctly realise in vitro. When, furthermore, the cellular function requires the interplay of more than one or two proteins, in vitro experiments for the analysis of this situation soon become complex. Instead, we thus try to obtain information on the molecular properties of proteins in the living cell. Then, the cell takes care of correct protein folding and modification. A series of molecular techniques are, and new ones become, available which allow for measuring molecular protein properties in the living cell, offering information on concentration (FCS), dynamics (FCS, RICS, FRAP), location (PALM, STED), interactions (F3H, FCCS) and protein proximities (FRET, BRET, FLIM, BiFC). Here, these techniques are presented with their advantages and drawbacks, with examples from our current kinetochore research. The review is supposed to give orientation to researchers planning to enter the field, and inform which techniques help us to gain molecular information on a multi-protein complex. We show that the field of cellular imaging is in a phase of transition: in the future, an increasing amount of physico-chemical data can be determined in the living cell. Copyright © 2013 Elsevier B.V. All rights reserved.

Molecular and genetic epidemiology of cancer in low- and medium-income countries.

PubMed

Malhotra, Jyoti

2014-01-01

Genetic and molecular factors can play an important role in an individual's cancer susceptibility and response to carcinogen exposure. Cancer susceptibility and response to carcinogen exposure can be either through inheritance of high penetrance but rare germline mutations that constitute heritable cancer syndromes, or it can be inherited as common genetic variations or polymorphisms that are associated with low to moderate risk for development of cancer. These polymorphisms can interact with environmental exposures and can influence an individual's cancer risk through multiple pathways, including affecting the rate of metabolism of carcinogens or the immune response to these toxins. Thus, these genetic polymorphisms can account for some of the geographical differences seen in cancer prevalence between different populations. This review explores the role of molecular epidemiology in the field of cancer prevention and control in low- and medium-income countries. Using data from Human Genome Project and HapMap Project, genome-wide association studies have been able to identify multiple susceptibility loci for different cancers. The field of genetic and molecular epidemiology has been further revolutionized by the discovery of newer, faster, and more efficient DNA-sequencing technologies including next-generation sequencing. The new DNA-sequencing technologies can play an important role in planning and implementation of cancer prevention and screening strategies. More research is needed in this area, especially in investigating new biomarkers and measuring gene-environment interactions. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Hydration free energies of cyanide and hydroxide ions from molecular dynamics simulations with accurate force fields

USGS Publications Warehouse

Lee, M.W.; Meuwly, M.

2013-01-01

The evaluation of hydration free energies is a sensitive test to assess force fields used in atomistic simulations. We showed recently that the vibrational relaxation times, 1D- and 2D-infrared spectroscopies for CN(-) in water can be quantitatively described from molecular dynamics (MD) simulations with multipolar force fields and slightly enlarged van der Waals radii for the C- and N-atoms. To validate such an approach, the present work investigates the solvation free energy of cyanide in water using MD simulations with accurate multipolar electrostatics. It is found that larger van der Waals radii are indeed necessary to obtain results close to the experimental values when a multipolar force field is used. For CN(-), the van der Waals ranges refined in our previous work yield hydration free energy between -72.0 and -77.2 kcal mol(-1), which is in excellent agreement with the experimental data. In addition to the cyanide ion, we also study the hydroxide ion to show that the method used here is readily applicable to similar systems. Hydration free energies are found to sensitively depend on the intermolecular interactions, while bonded interactions are less important, as expected. We also investigate in the present work the possibility of applying the multipolar force field in scoring trajectories generated using computationally inexpensive methods, which should be useful in broader parametrization studies with reduced computational resources, as scoring is much faster than the generation of the trajectories.

Large-scale compensation of errors in pairwise-additive empirical force fields: comparison of AMBER intermolecular terms with rigorous DFT-SAPT calculations.

PubMed

Zgarbová, Marie; Otyepka, Michal; Sponer, Jirí; Hobza, Pavel; Jurecka, Petr

2010-09-21

The intermolecular interaction energy components for several molecular complexes were calculated using force fields available in the AMBER suite of programs and compared with Density Functional Theory-Symmetry Adapted Perturbation Theory (DFT-SAPT) values. The extent to which such comparison is meaningful is discussed. The comparability is shown to depend strongly on the intermolecular distance, which means that comparisons made at one distance only are of limited value. At large distances the coulombic and van der Waals 1/r(6) empirical terms correspond fairly well with the DFT-SAPT electrostatics and dispersion terms, respectively. At the onset of electronic overlap the empirical values deviate from the reference values considerably. However, the errors in the force fields tend to cancel out in a systematic manner at equilibrium distances. Thus, the overall performance of the force fields displays errors an order of magnitude smaller than those of the individual interaction energy components. The repulsive 1/r(12) component of the van der Waals expression seems to be responsible for a significant part of the deviation of the force field results from the reference values. We suggest that further improvement of the force fields for intermolecular interactions would require replacement of the nonphysical 1/r(12) term by an exponential function. Dispersion anisotropy and its effects are discussed. Our analysis is intended to show that although comparing the empirical and non-empirical interaction energy components is in general problematic, it might bring insights useful for the construction of new force fields. Our results are relevant to often performed force-field-based interaction energy decompositions.

Bioinformatics and molecular modeling in glycobiology

PubMed Central

Schloissnig, Siegfried

2010-01-01

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed. PMID:20364395

Premelting, fluctuations, and coarse-graining of water-ice interfaces.

PubMed

Limmer, David T; Chandler, David

2014-11-14

Using statistical field theory supplemented with molecular dynamics simulations, we consider premelting on the surface of ice as a generic consequence of broken hydrogen bonds at the boundary between the condensed and gaseous phases. A procedure for coarse-graining molecular configurations onto a continuous scalar order parameter field is discussed, which provides a convenient representation of the interface between locally crystal-like and locally liquid-like regions. A number of interfacial properties are straightforwardly evaluated using this procedure such as the average premelting thickness and surface tension. The temperature and system size dependence of the premelting layer thickness calculated in this way confirms the characteristic logarithmic growth expected for the scalar field theory that the system is mapped onto through coarse-graining, though remains finite due to long-ranged interactions. Finally, from explicit simulations the existence of a premelting layer is shown to be insensitive to bulk lattice geometry, exposed crystal face, and curvature.

Premelting, fluctuations, and coarse-graining of water-ice interfaces

NASA Astrophysics Data System (ADS)

Limmer, David T.; Chandler, David

2014-11-01

Using statistical field theory supplemented with molecular dynamics simulations, we consider premelting on the surface of ice as a generic consequence of broken hydrogen bonds at the boundary between the condensed and gaseous phases. A procedure for coarse-graining molecular configurations onto a continuous scalar order parameter field is discussed, which provides a convenient representation of the interface between locally crystal-like and locally liquid-like regions. A number of interfacial properties are straightforwardly evaluated using this procedure such as the average premelting thickness and surface tension. The temperature and system size dependence of the premelting layer thickness calculated in this way confirms the characteristic logarithmic growth expected for the scalar field theory that the system is mapped onto through coarse-graining, though remains finite due to long-ranged interactions. Finally, from explicit simulations the existence of a premelting layer is shown to be insensitive to bulk lattice geometry, exposed crystal face, and curvature.

Magnetic field effect on the structural properties of a peptide model: Molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Housaindokht, Mohammad Reza; Moosavi, Fatemeh

2018-06-01

The effect of magnetization on the properties of a system containing a peptide model is studied by molecular dynamics simulation at a range of 298-318 K. Two mole fractions of 0.001 and 0.002 of peptide were simulated and the variation of hydrogen bond number, orientational ordering parameter, gyration radius, mean square displacement, as well as radial distribution function, were under consideration. The results show that applying magnetic field will increase the number of hydrogen bonds between water molecules by clustering them and decreases the interaction of water and peptide. This reduction may cause more available free space and enhance the movement of the peptide. As a result, the diffusion coefficient of the peptide becomes greater and its conformation changes. Orientational ordering parameter besides radius of gyration demonstrates that peptide is expanded by static magnetic field and its orientational ordering parameter is affected.

Theoretical study of asymmetric super-rotors: Alignment and orientation

NASA Astrophysics Data System (ADS)

Omiste, Juan J.

2018-02-01

We report a theoretical study of the optical centrifuge acceleration of an asymmetric top molecule interacting with an electric static field by solving the time-dependent Schrödinger equation in the rigid rotor approximation. A detailed analysis of the mixing of the angular momentum in both the molecular and the laboratory fixed frames allows us to deepen the understanding of the main features of the acceleration process, for instance, the effective angular frequency of the molecule at the end of the pulse. For the case of the SO2 molecular super-rotor, we show numerically that it rotates around one internal axis and that its dynamics is confined to the plane defined by the polarization axis of the laser, in agreement with experimental findings. Furthermore, we consider the orientation patterns induced by the dc field, showing the characteristics of their structure as a function of the strength of the static field and the initial configuration of the fields.

Polarizable atomic multipole-based force field for DOPC and POPE membrane lipids

NASA Astrophysics Data System (ADS)

Chu, Huiying; Peng, Xiangda; Li, Yan; Zhang, Yuebin; Min, Hanyi; Li, Guohui

2018-04-01

A polarizable atomic multipole-based force field for the membrane bilayer models 1,2-dioleoyl-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) has been developed. The force field adopts the same framework as the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) model, in which the charge distribution of each atom is represented by the permanent atomic monopole, dipole and quadrupole moments. Many-body polarization including the inter- and intra-molecular polarization is modelled in a consistent manner with distributed atomic polarizabilities. The van der Waals parameters were first transferred from existing AMOEBA parameters for small organic molecules and then optimised by fitting to ab initio intermolecular interaction energies between models and a water molecule. Molecular dynamics simulations of the two aqueous DOPC and POPE membrane bilayer systems, consisting of 72 model molecules, were then carried out to validate the force field parameters. Membrane width, area per lipid, volume per lipid, deuterium order parameters, electron density profile, etc. were consistent with experimental values.

Mechanics of water pore formation in lipid membrane under electric field

NASA Astrophysics Data System (ADS)

Bu, Bing; Li, Dechang; Diao, Jiajie; Ji, Baohua

2017-04-01

Transmembrane water pores are crucial for substance transport through cell membranes via membrane fusion, such as in neural communication. However, the molecular mechanism of water pore formation is not clear. In this study, we apply all-atom molecular dynamics and bias-exchange metadynamics simulations to study the process of water pore formation under an electric field. We show that water molecules can enter a membrane under an electric field and form a water pore of a few nanometers in diameter. These water molecules disturb the interactions between lipid head groups and the ordered arrangement of lipids. Following the movement of water molecules, the lipid head groups are rotated and driven into the hydrophobic region of the membrane. The reorientated lipid head groups inside the membrane form a hydrophilic surface of the water pore. This study reveals the atomic details of how an electric field influences the movement of water molecules and lipid head groups, resulting in water pore formation.

Near-Resonant Raman Amplification in the Rotational Quantum Wave Packets of Nitrogen Molecular Ions Generated by Strong Field Ionization

NASA Astrophysics Data System (ADS)

Liu, Zhaoxiang; Yao, Jinping; Chen, Jinming; Xu, Bo; Chu, Wei; Cheng, Ya

2018-02-01

The generation of laserlike narrow bandwidth emissions from nitrogen molecular ions (N2+ ) generated in intense near- and mid infrared femtosecond laser fields has aroused much interest because of the mysterious physics underlying such a phenomenon. Here, we perform a pump-probe measurement on the nonlinear interaction of rotational quantum wave packets of N2+ generated in midinfrared (e.g., at a wavelength centered at 1580 nm) femtosecond laser fields with an ultrashort probe pulse whose broad spectrum overlaps both P - and R -branch rotational transition lines between the electronic states N2+(B2Σu+,v'=0 ) and N2+(X2Σg+,v =0 ) . The results indicate the occurrence of highly efficient near-resonant stimulated Raman scattering in the quantum wave packets of N2+ ions generated in strong laser fields in the midinfrared region, of which the underlying mechanism is different from that of the air lasers generated in atmospheric environment when pumping with 800 nm intense pulses.

a Molecular Fountain

NASA Astrophysics Data System (ADS)

Cheng, Cunfeng; van der Poel, Aernout P. P.; Ubachs, Wim; Bethlem, Hendrick

2017-06-01

The resolution of any spectroscopic experiment is limited by the coherent interaction time between the probe radiation and the particle that is being studied. The introduction of cooling techniques for atoms and ions has resulted in a dramatic increase of interaction times and accuracy, it is hoped that molecular cooling techniques will lead to a similar increase. Here we demonstrate the first molecular fountain, a development which permits hitherto unattainably long interrogation times with molecules. In our experiment, beams of ammonia molecules are decelerated, trapped and cooled using inhomogeneous electric fields and subsequently launched. Using a combination of quadrupole lenses and buncher elements, the beam is shaped such that it has a large position spread and a small velocity spread (corresponding to a transverse temperature of less than 10μK and a longitudinal temperature of less than 1μK) while the molecules are in free fall, but strongly focused at the detection region. The molecules are in free fall for up to 266 milliseconds, making it possible, in principle, to perform sub-Hz measurements in molecular systems and paving the way for stringent tests of fundamental physics theories.

High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations

PubMed Central

Chen, Alan A.; García, Angel E.

2013-01-01

We report the de novo folding of three hyperstable RNA tetraloops to 1–3 Å rmsd from their experimentally determined structures using molecular dynamics simulations initialized in the unfolded state. RNA tetraloops with loop sequences UUCG, GCAA, or CUUG are hyperstable because of the formation of noncanonical loop-stabilizing interactions, and they are all faithfully reproduced to angstrom-level accuracy in replica exchange molecular dynamics simulations, including explicit solvent and ion molecules. This accuracy is accomplished using unique RNA parameters, in which biases that favor rigid, highly stacked conformations are corrected to accurately capture the inherent flexibility of ssRNA loops, accurate base stacking energetics, and purine syn-anti interconversions. In a departure from traditional quantum chemistrycentric approaches to force field optimization, our parameters are calibrated directly from thermodynamic and kinetic measurements of intra- and internucleotide structural transitions. The ability to recapitulate the signature noncanonical interactions of the three most abundant hyperstable stem loop motifs represents a significant milestone to the accurate prediction of RNA tertiary structure using unbiased all-atom molecular dynamics simulations. PMID:24043821

Molecular dynamics simulations of aqueous solutions of ethanolamines.

PubMed

López-Rendón, Roberto; Mora, Marco A; Alejandre, José; Tuckerman, Mark E

2006-08-03

We report on molecular dynamics simulations performed at constant temperature and pressure to study ethanolamines as pure components and in aqueous solutions. A new geometric integration algorithm that preserves the correct phase space volume is employed to study molecules having up to three ethanol chains. The most stable geometry, rotational barriers, and atomic charges were obtained by ab initio calculations in the gas phase. The calculated dipole moments agree well with available experimental data. The most stable conformation, due to intramolecular hydrogen bonding interactions, has a ringlike structure in one of the ethanol chains, leading to high molecular stability. All molecular dynamics simulations were performed in the liquid phase. The interaction parameters are the same for the atoms in the ethanol chains, reducing the number of variables in the potential model. Intermolecular hydrogen bonding is also analyzed, and it is shown that water associates at low water mole fractions. The force field reproduced (within 1%) the experimental liquid densities at different temperatures of pure components and aqueous solutions at 313 K. The excess and partial molar volumes are analyzed as a function of ethanolamine concentration.

Molecular dynamics simulations of acoustic absorption by a carbon nanotube

NASA Astrophysics Data System (ADS)

Ayub, M.; Zander, A. C.; Huang, D. M.; Howard, C. Q.; Cazzolato, B. S.

2018-06-01

Acoustic absorption by a carbon nanotube (CNT) was studied using molecular dynamics (MD) simulations in a molecular domain containing a monatomic gas driven by a time-varying periodic force to simulate acoustic wave propagation. Attenuation of the sound wave and the characteristics of the sound field due to interactions with the CNT were studied by evaluating the behavior of various acoustic parameters and comparing the behavior with that of the domain without the CNT present. A standing wave model was developed for the CNT-containing system to predict sound attenuation by the CNT and the results were verified against estimates of attenuation using the thermodynamic concept of exergy. This study demonstrates acoustic absorption effects of a CNT in a thermostatted MD simulation, quantifies the acoustic losses induced by the CNT, and illustrates their effects on the CNT. Overall, a platform was developed for MD simulations that can model acoustic damping induced by nanostructured materials such as CNTs, which can be used for further understanding of nanoscale acoustic loss mechanisms associated with molecular interactions between acoustic waves and nanomaterials.

Atom-bond electronegativity equalization method fused into molecular mechanics. I. A seven-site fluctuating charge and flexible body water potential function for water clusters.

PubMed

Yang, Zhong-Zhi; Wu, Yang; Zhao, Dong-Xia

2004-02-08

Recently, experimental and theoretical studies on the water system are very active and noticeable. A transferable intermolecular potential seven points approach including fluctuation charges and flexible body (ABEEM-7P) based on a combination of the atom-bond electronegativity equalization and molecular mechanics (ABEEM/MM), and its application to small water clusters are explored and tested in this paper. The consistent combination of ABEEM and molecular mechanics (MM) is to take the ABEEM charges of atoms, bonds, and lone-pair electrons into the intermolecular electrostatic interaction term in molecular mechanics. To examine the charge transfer we have used two models coming from the charge constraint types: one is a charge neutrality constraint on whole water system and the other is on each water molecule. Compared with previous water force fields, the ABEEM-7P model has two characters: (1) the ABEEM-7P model not only presents the electrostatic interaction of atoms, bonds and lone-pair electrons and their changing in respond to different ambient environment but also introduces "the hydrogen bond interaction region" in which a new parameter k(lp,H)(R(lp,H)) is used to describe the electrostatic interaction of the lone-pair electron and the hydrogen atom which can form the hydrogen bond; (2) nonrigid but flexible water body permitting the vibration of the bond length and angle is allowed due to the combination of ABEEM and molecular mechanics, and for van der Waals interaction the ABEEM-7P model takes an all atom-atom interaction, i.e., oxygen-oxygen, hydrogen-hydrogen, oxygen-hydrogen interaction into account. The ABEEM-7P model based on ABEEM/MM gives quite accurate predictions for gas-phase state properties of the small water clusters (H(2)O)(n) (n=2-6), such as optimized geometries, monomer dipole moments, vibrational frequencies, and cluster interaction energies. Due to its explicit description of charges and the hydrogen bond, the ABEEM-7P model will be applied to discuss properties of liquid water, ice, aqueous solutions, and biological systems.

Selection of Amino Acid Chirality via Neutrino Interactions with 14N in Crossed Electric and Magnetic Fields

PubMed Central

Boyd, Richard N.; Kajino, Toshitaka; Onaka, Takashi

2018-01-01

Abstract Previous work has suggested that the chirality of the amino acids could be established in the magnetic field of a nascent neutron star from a core-collapse supernova or massive collapsar. The magnetic field would orient the 14N nuclei, and the alignment of its nuclear spin with respect to those of the electron antineutrinos emitted from the collapsing star would determine the probability of destruction of the 14N nuclei by interactions with the antineutrinos. Subsequent work estimated the bulk polarization of the 14N nuclei in large rotating meteoroids in such an environment. The present work adds a crucial piece of this model by describing the details by which the selective 14N nuclear destruction would produce molecular chiral selectivity. The effects of the neutrino-induced interactions on the 14N nuclei bound in amino acids polarized in strong magnetic fields are studied. It is shown that electric fields in the reference frame of the nuclei modify the magnetic field at the nucleus, creating nuclear magnetizations that are asymmetric in chirality. The antineutrino cross sections depend on this magnetization, creating a selective destructive effect. The environmental conditions and sites in which such a selection mechanism could occur are discussed. Selective destruction of D-enantiomers results in enantiomeric excesses which may be sufficient to drive subsequent autocatalysis necessary to produce the few-percent enantiomeric excesses found in meteorites and subsequent homochirality. Molecular quantum chemical calculations were performed for alanine, and the chirality-dependent effects studied were included. A preference for left-handed molecules was found, and enantiomeric excesses as high as 0.02% were estimated for molecules in the electromagnetic conditions expected from a core-collapse supernova. Key Words: Amino acids—Supernovae—Antineutrinos—Enantiomeric excess—Chirality. Astrobiology 18, 190–206. PMID:29160728

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

PubMed Central

Pamenter, Matthew E.; Powell, Frank L.

2016-01-01

Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

Covalent intermolecular interaction of the nitric oxide dimer (NO)2

NASA Astrophysics Data System (ADS)

Zhang, Hui; Zheng, Gui-Li; Lv, Gang; Geng, Yi-Zhao; Ji, Qing

2015-09-01

Covalent bonds arise from the overlap of the electronic clouds in the internucleus region, which is a pure quantum effect and cannot be obtained in any classical way. If the intermolecular interaction is of covalent character, the result from direct applications of classical simulation methods to the molecular system would be questionable. Here, we analyze the special intermolecular interaction between two NO molecules based on quantum chemical calculation. This weak intermolecular interaction, which is of covalent character, is responsible for the formation of the NO dimer, (NO)2, in its most stable conformation, a cis conformation. The natural bond orbital (NBO) analysis gives an intuitive illustration of the formation of the dimer bonding and antibonding orbitals concomitant with the breaking of the π bonds with bond order 0.5 of the monomers. The dimer bonding is counteracted by partially filling the antibonding dimer orbital and the repulsion between those fully or nearly fully occupied nonbonding dimer orbitals that make the dimer binding rather weak. The direct molecular mechanics (MM) calculation with the UFF force fields predicts a trans conformation as the most stable state, which contradicts the result of quantum mechanics (QM). The lesson from the investigation of this special system is that for the case where intermolecular interaction is of covalent character, a specific modification of the force fields of the molecular simulation method is necessary. Project supported by the National Natural Science Foundation of China (Grant Nos. 90403007 and 10975044), the Key Subject Construction Project of Hebei Provincial Universities, China, the Research Project of Hebei Education Department, China (Grant Nos. Z2012067 and Z2011133), the National Natural Science Foundation of China (Grant No. 11147103), and the Open Project Program of State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, China (Grant No. Y5KF211CJ1).

Computer simulation and experimental self-assembly of irradiated glycine amino acid under magnetic fields: Its possible significance in prebiotic chemistry.

PubMed

Heredia, Alejandro; Colín-García, María; Puig, Teresa Pi I; Alba-Aldave, Leticia; Meléndez, Adriana; Cruz-Castañeda, Jorge A; Basiuk, Vladimir A; Ramos-Bernal, Sergio; Mendoza, Alicia Negrón

2017-12-01

Ionizing radiation may have played a relevant role in chemical reactions for prebiotic biomolecule formation on ancient Earth. Environmental conditions such as the presence of water and magnetic fields were possibly relevant in the formation of organic compounds such as amino acids. ATR-FTIR, Raman, EPR and X-ray spectroscopies provide valuable information about molecular organization of different glycine polymorphs under static magnetic fields. γ-glycine polymorph formation increases in irradiated samples interacting with static magnetic fields. The increase in γ-glycine polymorph agrees with the computer simulations. The AM1 semi-empirical simulations show a change in the catalyst behavior and dipole moment values in α and γ-glycine interaction with the static magnetic field. The simulated crystal lattice energy in α-glycine is also affected by the free radicals under the magnetic field, which decreases its stability. Therefore, solid α and γ-glycine containing free radicals under static magnetic fields might have affected the prebiotic scenario on ancient Earth by causing the oligomerization of glycine in prebiotic reactions. Copyright © 2017 Elsevier B.V. All rights reserved.

New observational insight on shock interactions toward supernovae and supernova remnants

NASA Astrophysics Data System (ADS)

Kilpatrick, Charles Donald

2016-08-01

Supernovae (SNe) are energetic explosions that signal the end of a star's life. These events and the supernova remnants (SNRs) they leave behind play a central role in stellar feedback by adding energy and momentum and metals to the interstellar medium (ISM). Emission associated with these feedback processes, especially atomic and molecular line emission as well as thermal and nonthermal continuum emission is known to be enhanced in regions of high density, such as dense circumstellar matter (CSM) around SNe and molecular clouds (MCs). In this thesis, I begin with a brief overview of the physics of SN shocks in Chapter 1, focusing on a foundation for studying pan-chromatic signatures of interactions between SNe and dense environments. In Chapter 2, I examine an unusual SN with signatures of CSM interaction in the form of narrow lines of hydrogen (Type IIn) and thermal continuum emission. This SN appears to belong to a class of Type Ia SNe that shares spectroscopic features with Type IIn SNe. I discuss the difficulties of decomposing spectra in a regime where interaction occurs between SN ejecta and CSM, potentially confusing the underlying SN type. This is followed by a discussion of rebrightening that occurred at late-time in B and V band photometry of this SN, possibly associated with clumpy or dense CSM at large distances from the progenitor. In Chapter 3, I examine synchrotron emission from Cassiopeia A, observed in the Ks band over multiple epochs. The synchrotron emission is generally diffuse over the remnant, but there is one location in the southwest portion of the remnant where it appears to be enhanced and entrained as knots of emission in the SNR ejecta. I evaluate whether the Ks band knots are dominated by synchrotron emission by comparing them to other infrared and radio imaging that is known to be dominated by synchrotron emission. Concluding that they are likely synchrotron-emitting knots, I measure the magnetic field strength and electron density required for their evolution over the ˜10 yr baseline they were observed and find B 1.3 - 5.8 mG and ne ≈ 1,000 - 15,000 cm-3. The magnetic field strengths appear enhanced beyond values required by the adiabatic strong shock limit, arguing in favor of other forms of magnetic field amplification in the shock. In Chapter 4, I again discuss Cassiopeia A and interaction between the remnant and nearby MCs as seen at mid-infrared and millimeter wavelengths. I report detection of a SNR-MC interaction and analyze its signatures in broadened molecular lines. I extend this analysis in Chapter 5 to a large survey for SNR-MC interactions in the 12CO J = 2 - 1 line. Although broadened 12CO J = 2 - 1 line emission should be detectable toward virtually all SNR-MC interactions, I find relatively few examples; therefore, the number of interactions is low. This result favors mechanisms other than supernova feedback as the basic trigger for star formation. In addition, I find no significant association between TeV gamma-ray sources and MC interactions, contrary to predictions that SNR-MC interfaces are the primary venues for cosmic ray acceleration. I end this dissertation in Chapter 6 with a brief summary of my results and two extensions of this work: examining the late-time radio light curves of CSM-interacting SNe for signatures of radio synchrotron emission and dense or clumpy CSM at large distances from the progenitor and re-observing SNR-MC interactions in 12CO J = 3 - 2 in order to verify the presence of shock-heated molecular gas and perform a census on the densities and temperatures of post-shock molecular gas.

Charging of a conducting sphere in a weakly ionized collisional plasma: Temporal dynamics and stationary state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grach, V. S., E-mail: vsgrach@app.sci-nnov.ru; Garasev, M. A.

2015-07-15

We consider the interaction of a isolated conducting sphere with a collisional weakly ionized plasma in an external field. We assume that the plasma consists of two species of ions neglecting of electrons. We take into account charging of the sphere due to sedimentation of plasma ions on it, the field of the sphere charge and the space charge, as well as recombination and molecular diffusion. The nonstationary problem of interaction of the sphere with the surrounding plasma is solved numerically. The temporal dynamics of the sphere charge and plasma perturbations is analyzed, as well as the properties of themore » stationary state. It is shown that the duration of transient period is determined by the recombination time and by the reverse conductivity of ions. The temporal dynamics of the sphere charge and plasma perturbations is determined by the intensity of recombination processes relative to the influence of the space charge field and diffusion. The stationary absolute value of the sphere charge increases linearly with the external electric field, decreases with the relative intensity of recombination processes and increases in the presence of substantial diffusion. The scales of the perturbed region in the plasma are determined by the radius of the sphere, the external field, the effect of diffusion, and the relative intensity of recombination processes. In the limiting case of the absence of molecular diffusion and a strong external field, the properties of the stationary state coincide with those obtained earlier as a result of approximate solution.« less

Electric-field-driven electron-transfer in mixed-valence molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blair, Enrique P., E-mail: enrique-blair@baylor.edu; Corcelli, Steven A., E-mail: scorcell@nd.edu; Lent, Craig S., E-mail: lent@nd.edu

2016-07-07

Molecular quantum-dot cellular automata is a computing paradigm in which digital information is encoded by the charge configuration of a mixed-valence molecule. General-purpose computing can be achieved by arranging these compounds on a substrate and exploiting intermolecular Coulombic coupling. The operation of such a device relies on nonequilibrium electron transfer (ET), whereby the time-varying electric field of one molecule induces an ET event in a neighboring molecule. The magnitude of the electric fields can be quite large because of close spatial proximity, and the induced ET rate is a measure of the nonequilibrium response of the molecule. We calculate themore » electric-field-driven ET rate for a model mixed-valence compound. The mixed-valence molecule is regarded as a two-state electronic system coupled to a molecular vibrational mode, which is, in turn, coupled to a thermal environment. Both the electronic and vibrational degrees-of-freedom are treated quantum mechanically, and the dissipative vibrational-bath interaction is modeled with the Lindblad equation. This approach captures both tunneling and nonadiabatic dynamics. Relationships between microscopic molecular properties and the driven ET rate are explored for two time-dependent applied fields: an abruptly switched field and a linearly ramped field. In both cases, the driven ET rate is only weakly temperature dependent. When the model is applied using parameters appropriate to a specific mixed-valence molecule, diferrocenylacetylene, terahertz-range ET transfer rates are predicted.« less

Architectonics: Design of Molecular Architecture for Functional Applications.

PubMed

Avinash, M B; Govindaraju, Thimmaiah

2018-02-20

The term architectonics has its roots in the architectural and philosophical (as early as 1600s) literature that refers to "the theory of structure" and "the structure of theory", respectively. The concept of architectonics has been adapted to advance the field of molecular self-assembly and termed as molecular architectonics. In essence, the methodology of organizing molecular units in the required and controlled configurations to develop advanced functional systems for materials and biological applications comprises the field of molecular architectonics. This concept of designing noncovalent systems enables to focus on different functional aspects of designer molecules for biological and nonbiological applications and also strengthens our efforts toward the mastery over the art of controlled molecular self-assemblies. Programming complex molecular interactions and assemblies for specific functions has been one of the most challenging tasks in the modern era. Meticulously ordered molecular assemblies can impart remarkable developments in several areas spanning energy, health, and environment. For example, the well-defined nano-, micro-, and macroarchitectures of functional molecules with specific molecular ordering possess potential applications in flexible electronics, photovoltaics, photonic crystals, microreactors, sensors, drug delivery, biomedicine, and superhydrophobic coatings, among others. The functional molecular architectures having unparalleled properties are widely evident in various designs of Nature. By drawing inspirations from Nature, intended molecular architectures can be designed and developed to harvest various functions, as there is an inexhaustible resource and scope. In this Account, we present exquisite designer molecules developed by our group and others with an objective to master the art of molecular recognition and self-assembly for functional applications. We demonstrate the tailor-ability of molecular self-assemblies by employing biomolecules like amino acids and nucleobases as auxiliaries. Naphthalenediimide (NDI), perylenediimide (PDI), and few other molecular systems serve as functional modules. The effects of stereochemistry and minute structural modifications in the molecular designs on the supramolecular interactions, and construction of self-assembled zero-dimensional (OD), one-dimensional (1D), and two-dimensional (2D) nano- and microarchitectures like particles, spheres, cups, bowls, fibers, belts, helical belts, supercoiled helices, sheets, fractals, and honeycomb-like arrays are discussed in extensive detail. Additionally, we present molecular systems that showcase the elegant designs of coassembly, templated assembly, hierarchical assembly, transient self-assembly, chiral denaturation, retentive helical memory, self-replication, supramolecular regulation, supramolecular speciation, supernon linearity, dynamic pathway complexity, supramolecular heterojunction, living supramolecular polymerization, and molecular machines. Finally, we describe the molecular engineering principles learnt over the years that have led to several applications, namely, organic electronics, self-cleaning, high-mechanical strength, and tissue engineering.

Specificity of molecular interactions in transient protein-protein interaction interfaces.

PubMed

Cho, Kyu-il; Lee, KiYoung; Lee, Kwang H; Kim, Dongsup; Lee, Doheon

2006-11-15

In this study, we investigate what types of interactions are specific to their biological function, and what types of interactions are persistent regardless of their functional category in transient protein-protein heterocomplexes. This is the first approach to analyze protein-protein interfaces systematically at the molecular interaction level in the context of protein functions. We perform systematic analysis at the molecular interaction level using classification and feature subset selection technique prevalent in the field of pattern recognition. To represent the physicochemical properties of protein-protein interfaces, we design 18 molecular interaction types using canonical and noncanonical interactions. Then, we construct input vector using the frequency of each interaction type in protein-protein interface. We analyze the 131 interfaces of transient protein-protein heterocomplexes in PDB: 33 protease-inhibitors, 52 antibody-antigens, 46 signaling proteins including 4 cyclin dependent kinase and 26 G-protein. Using kNN classification and feature subset selection technique, we show that there are specific interaction types based on their functional category, and such interaction types are conserved through the common binding mechanism, rather than through the sequence or structure conservation. The extracted interaction types are C(alpha)-- H...O==C interaction, cation...anion interaction, amine...amine interaction, and amine...cation interaction. With these four interaction types, we achieve the classification success rate up to 83.2% with leave-one-out cross-validation at k = 15. Of these four interaction types, C(alpha)--H...O==C shows binding specificity for protease-inhibitor complexes, while cation-anion interaction is predominant in signaling complexes. The amine ... amine and amine...cation interaction give a minor contribution to the classification accuracy. When combined with these two interactions, they increase the accuracy by 3.8%. In the case of antibody-antigen complexes, the sign is somewhat ambiguous. From the evolutionary perspective, while protease-inhibitors and sig-naling proteins have optimized their interfaces to suit their biological functions, antibody-antigen interactions are the happenstance, implying that antibody-antigen complexes do not show distinctive interaction types. Persistent interaction types such as pi...pi, amide-carbonyl, and hydroxyl-carbonyl interaction, are also investigated. Analyzing the structural orientations of the pi...pi stacking interactions, we find that herringbone shape is a major configuration in transient protein-protein interfaces. This result is different from that of protein core, where parallel-displaced configurations are the major configuration. We also analyze overall trend of amide-carbonyl and hydroxyl-carbonyl interactions. It is noticeable that nearly 82% of the interfaces have at least one hydroxyl-carbonyl interactions. (c) 2006 Wiley-Liss, Inc.

Interaction between holo transferrin and HSA-PPIX complex in the presence of lomefloxacin: An evaluation of PPIX aggregation in protein-protein interactions

NASA Astrophysics Data System (ADS)

Sattar, Zohreh; Iranfar, Hediye; Asoodeh, Ahmad; Saberi, Mohammad Reza; Mazhari, Mahboobeh; Chamani, Jamshidkhan

2012-11-01

Human serum albumin (HSA) and holo transferrin (TF) are two serum carrier proteins that are able to interact with each other, thereby altering their binding behavior toward their ligands. During the course of this study, the interaction between HSA-PPIX and TF, in the presence and absence of lomefloxacin (LMF), was for the first time investigated using different spectroscopic and molecular modeling techniques. Fluorescence spectroscopy experiments were performed in order to study conformational changes of proteins. The RLS technique was utilized to investigate the effect of LMF on J-aggregation of PPIX, which is the first report of its kind. Our findings present clear-cut evidence for the alteration of interactions between HSA and TF in the presence of PPIX and changes in drug-binding to HSA and HSA-PPIX complex upon interaction with TF. Moreover, molecular modeling studies suggested that the binding site for LMF became switched in the presence of PPIX, and that LMF bound to the site IIA of HSA. The obtained results should give new insight into research in this field and may cast some light on the dynamics of drugs in biological systems.

Source-sink interaction: a century old concept under the light of modern molecular systems biology.

PubMed

Chang, Tian-Gen; Zhu, Xin-Guang; Raines, Christine

2017-07-20

Many approaches to engineer source strength have been proposed to enhance crop yield potential. However, a well-co-ordinated source-sink relationship is required finally to realize the promised increase in crop yield potential in the farmer's field. Source-sink interaction has been intensively studied for decades, and a vast amount of knowledge about the interaction in different crops and under different environments has been accumulated. In this review, we first introduce the basic concepts of source, sink and their interactions, then summarize current understanding of how source and sink can be manipulated through both environmental control and genetic manipulations. We show that the source-sink interaction underlies the diverse responses of crops to the same perturbations and argue that development of a molecular systems model of source-sink interaction is required towards a rational manipulation of the source-sink relationship for increased yield. We finally discuss both bottom-up and top-down routes to develop such a model and emphasize that a community effort is needed for development of this model. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Evaluating experimental molecular physics studies of radiation damage in DNA*

NASA Astrophysics Data System (ADS)

Śmiałek, Małgorzata A.

2016-11-01

The field of Atomic and Molecular Physics (AMP) is a mature field exploring the spectroscopy, excitation, ionisation of atoms and molecules in all three phases. Understanding of the spectroscopy and collisional dynamics of AMP has been fundamental to the development and application of quantum mechanics and is applied across a broad range of disparate disciplines including atmospheric sciences, astrochemistry, combustion and environmental science, and in central to core technologies such as semiconductor fabrications, nanotechnology and plasma processing. In recent years the molecular physics also started significantly contributing to the area of the radiation damage at molecular level and thus cancer therapy improvement through both experimental and theoretical advances, developing new damage measurement and analysis techniques. It is therefore worth to summarise and highlight the most prominent findings from the AMP community that contribute towards better understanding of the fundamental processes in biologically-relevant systems as well as to comment on the experimental challenges that were met for more complex investigation targets. Contribution to the Topical Issue "Low-Energy Interactions related to Atmospheric and Extreme Conditions", edited by S. Ptasinska, M. Smialek-Telega, A. Milosavljevic, B. Sivaraman.

Moonlighting Proteins and Protein–Protein Interactions as Neurotherapeutic Targets in the G Protein-Coupled Receptor Field

PubMed Central

Fuxe, Kjell; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Palkovits, Miklós; Tarakanov, Alexander O; Ciruela, Francisco; Agnati, Luigi F

2014-01-01

There is serious interest in understanding the dynamics of the receptor–receptor and receptor–protein interactions in space and time and their integration in GPCR heteroreceptor complexes of the CNS. Moonlighting proteins are special multifunctional proteins because they perform multiple autonomous, often unrelated, functions without partitioning into different protein domains. Moonlighting through receptor oligomerization can be operationally defined as an allosteric receptor–receptor interaction, which leads to novel functions of at least one receptor protomer. GPCR-mediated signaling is a more complicated process than previously described as every GPCR and GPCR heteroreceptor complex requires a set of G protein interacting proteins, which interacts with the receptor in an orchestrated spatio-temporal fashion. GPCR heteroreceptor complexes with allosteric receptor–receptor interactions operating through the receptor interface have become major integrative centers at the molecular level and their receptor protomers act as moonlighting proteins. The GPCR heteroreceptor complexes in the CNS have become exciting new targets for neurotherapeutics in Parkinson's disease, schizophrenia, drug addiction, and anxiety and depression opening a new field in neuropsychopharmacology. PMID:24105074

Computer Simulations of Epoxy Adhesive Monomer Interactions with Alumina Surfaces

DTIC Science & Technology

1992-08-01

using Sybyl"’ molecular modeling software 9 on a Digital Equipment Corporation microVAXw cluster. The Tripos force field was employed in the...Ave, N, Ft Leonard Wood, MO 65473-5000 1 ATM- Libary Commander, US. Army Enginer Waterways Expenment Station, P.O. Box 631, Vicksburg, MS 39180 1 ATTN

Nucleic acids: theory and computer simulation, Y2K.

PubMed

Beveridge, D L; McConnell, K J

2000-04-01

Molecular dynamics simulations on DNA and RNA that include solvent are now being performed under realistic environmental conditions of water activity and salt. Improvements to force-fields and treatments of long-range interactions have significantly increased the reliability of simulations. New studies of sequence effects, axis bending, solvation and conformational transitions have appeared.

Understanding the physiological and molecular mechanisms of rice-microbial interactions that produce methane

USDA-ARS?s Scientific Manuscript database

The second most abundant greenhouse gas, methane, is ~25 times more potent in global warming potential than carbon dioxide, and 7-17% of atmospheric methane comes from flooded rice fields. Methane emissions can be greatly reduced by using alternate wetting and drying irrigation management and/or cul...

Dynamical properties of magnetized two-dimensional one-component plasma

NASA Astrophysics Data System (ADS)

Dubey, Girija S.; Gumbs, Godfrey; Fessatidis, Vassilios

2018-05-01

Molecular dynamics simulation are used to examine the effect of a uniform perpendicular magnetic field on a two-dimensional interacting electron system. In this simulation we include the effect of the magnetic field classically through the Lorentz force. Both the Coulomb and the magnetic forces are included directly in the electron dynamics to study their combined effect on the dynamical properties of the 2D system. Results are presented for the velocity autocorrelation function and the diffusion constants in the presence and absence of an external magnetic field. Our simulation results clearly show that the external magnetic field has an effect on the dynamical properties of the system.

Molecular dynamics simulation of highly charged proteins: Comparison of the particle-particle particle-mesh and reaction field methods for the calculation of electrostatic interactions

PubMed Central

Gargallo, Raimundo; Hünenberger, Philippe H.; Avilés, Francesc X.; Oliva, Baldomero

2003-01-01

Molecular dynamics (MD) simulations of the activation domain of porcine procarboxypeptidase B (ADBp) were performed to examine the effect of using the particle-particle particle-mesh (P3M) or the reaction field (RF) method for calculating electrostatic interactions in simulations of highly charged proteins. Several structural, thermodynamic, and dynamic observables were derived from the MD trajectories, including estimated entropies and solvation free energies and essential dynamics (ED). The P3M method leads to slightly higher atomic positional fluctuations and deviations from the crystallographic structure, along with somewhat lower values of the total energy and solvation free energy. However, the ED analysis of the system leads to nearly identical results for both simulations. Because of the strong similarity between the results, both methods appear well suited for the simulation of highly charged globular proteins in explicit solvent. However, the lower computational demand of the RF method in the present implementation represents a clear advantage over the P3M method. PMID:14500874

Nanofibre optic force transducers with sub-piconewton resolution via near-field plasmon–dielectric interactions

PubMed Central

Huang, Qian; Lee, Joon; Arce, Fernando Teran; Yoon, Ilsun; Angsantikul, Pavimol; Liu, Justin; Shi, Yuesong; Villanueva, Josh; Thamphiwatana, Soracha; Ma, Xuanyi; Zhang, Liangfang; Chen, Shaochen; Lal, Ratnesh; Sirbuly, Donald J.

2018-01-01

Ultrasensitive nanomechanical instruments, including the atomic force microscope (AFM)1–4 and optical and magnetic tweezers5–8, have helped shed new light on the complex mechanical environments of biological processes. However, it is difficult to scale down the size of these instruments due to their feedback mechanisms9, which, if overcome, would enable high-density nanomechanical probing inside materials. A variety of molecular force probes including mechanophores10, quantum dots11, fluorescent pairs12,13 and molecular rotors14–16 have been designed to measure intracellular stresses; however, fluorescence-based techniques can have short operating times due to photo-instability and it is still challenging to quantify the forces with high spatial and mechanical resolution. Here, we develop a compact nanofibre optic force transducer (NOFT) that utilizes strong near-field plasmon–dielectric interactions to measure local forces with a sensitivity of <200 fN. The NOFT system is tested by monitoring bacterial motion and heart-cell beating as well as detecting infrasound power in solution. PMID:29576804

Theoretical prediction of mutual influence between phospholipid and nanotube during their interaction

NASA Astrophysics Data System (ADS)

Glukhova, O. E.; Slepchenkov, M. M.

2016-03-01

Using hybrid quantum mechanics/molecular mechanics (QM/MM) model we carried out investigation of interaction between phospholipid and carbon nanotube during indentation of high density lipoprotein (HDL). The object of investigation is armchair carbon nanotube with various diameters range from 0.5 to 1 nm. In a coarse of molecular dynamics study it is found that phospholipid partially penetrate into the cavity of nanotube with the chirality (7,7) and diameter of 0.9 nm. However, the entire molecule does not fit into nanospace of tube (7,7), so part of the head and the second phospholipid tail remain outside the carbon nanostructures. Using semi-empirical PM6 method it is established that during the indentation process the charged structured molecule fragments forming the high-density lipoprotein create local electric field near carbon nanotube (CNT) and continuously change electronic structure of CNT. However, the tube is not destroyed because the fields do not exceed the critical values of strength. The redistribution of the electron density on atom is observed in each time point.

Force Field Accelerated Density Functional Theory Molecular Dynamics for Simulation of Reactive Systems at Extreme Conditions

NASA Astrophysics Data System (ADS)

Lindsey, Rebecca; Goldman, Nir; Fried, Laurence

Understanding chemistry at extreme conditions is crucial in fields including geochemistry, astrobiology, and alternative energy. First principles methods can provide valuable microscopic insights into such systems while circumventing the risks of physical experiments, however the time and length scales associated with chemistry at extreme conditions (ns and μm, respectively) largely preclude extension of such models to molecular dynamics. In this work, we develop a simulation approach that retains the accuracy of density functional theory (DFT) while decreasing computational effort by several orders of magnitude. We generate n-body descriptions for atomic interactions by mapping forces arising from short density functional theory (DFT) trajectories on to simple Chebyshev polynomial series. We examine the importance of including greater than 2-body interactions, model transferability to different state points, and discuss approaches to ensure smooth and reasonable model shape outside of the distance domain sampled by the DFT training set. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Manipulating Energy Flow at the Nanoscale by Coupling Plasmons of Metal Nanostructures to Resonant Molecules

NASA Astrophysics Data System (ADS)

Wiederrecht, Gary

2014-03-01

Collective hybrid excitations resulting from the coupling of metal nanostructures with organic molecules present unique opportunities for manipulating light-matter interactions at the nanoscale. In this talk, I discuss recent studies that are examples of the breadth of phenomena that are possible. First, the interactions of coupled plasmonic nanostructures with azobenzene-based polymers are described, in which the spatial features of the plasmonic near-field can be used to manipulate molecular motion. The directional molecular transport that results is shown to be useful for imaging the spatial and polarization features of the optical near-field. The modeling of this effect is described. Second, the coupling of excitonic molecular aggregates to metal nanostructures produces coherent coupling that provides added structure to the optical extinction spectra of metal nanoparticles, thereby by providing a photonic handle with which to manipulate energy flow on an ultrafast timescale. Monitoring the rate of energy flow as a function of photon energy reveals important information about the energy dissipation channels and the structural interactions between molecule and metal. Third, the strongly enhanced optical nonlinearity resulting from coupled plasmonic nanorods is described. The closely spaced nanorod material exhibits nonlocality of the optical response that has an unusually strong nonlinear dependence on incident light intensity. Electromagnetic modeling confirms the nonlocal response of the plasmonic metamaterial. The broader impact of collective hybrid excitations on nanophotonics applications is described. Use of the Center for Nanoscale Materials was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-06CH11357.

Circadian clocks in the cnidaria: environmental entrainment, molecular regulation, and organismal outputs.

PubMed

Reitzel, Adam M; Tarrant, Ann M; Levy, Oren

2013-07-01

The circadian clock is a molecular network that translates predictable environmental signals, such as light levels, into organismal responses, including behavior and physiology. Regular oscillations of the molecular components of the clock enable individuals to anticipate regularly fluctuating environmental conditions. Cnidarians play important roles in benthic and pelagic marine environments and also occupy a key evolutionary position as the likely sister group to the bilaterians. Together, these attributes make members of this phylum attractive as models for testing hypotheses on roles for circadian clocks in regulating behavior, physiology, and reproduction as well as those regarding the deep evolutionary conservation of circadian regulatory pathways in animal evolution. Here, we review and synthesize the field of cnidarian circadian biology by discussing the diverse effects of daily light cycles on cnidarians, summarizing the molecular evidence for the conservation of a bilaterian-like circadian clock in anthozoan cnidarians, and presenting new empirical data supporting the presence of a conserved feed-forward loop in the starlet sea anemone, Nematostella vectensis. Furthermore, we discuss critical gaps in our current knowledge about the cnidarian clock, including the functions directly regulated by the clock and the precise molecular interactions that drive the oscillating gene-expression patterns. We conclude that the field of cnidarian circadian biology is moving rapidly toward linking molecular mechanisms with physiology and behavior.

Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase.

PubMed

Liu, C Tony; Layfield, Joshua P; Stewart, Robert J; French, Jarrod B; Hanoian, Philip; Asbury, John B; Hammes-Schiffer, Sharon; Benkovic, Stephen J

2014-07-23

Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site. The electrostatics and degree of hydration of the microenvironments surrounding the probes are investigated with spectroscopic techniques and mixed quantum mechanical/molecular mechanical (QM/MM) calculations. Changes in the electrostatic microenvironments along the catalytic environment lead to different nitrile (CN) vibrational stretching frequencies and (13)C NMR chemical shifts. These environmental changes arise from protein conformational rearrangements during catalysis. The QM/MM calculations reproduce the experimentally measured vibrational frequency shifts of the thiocyanate probes across the catalyzed hydride transfer step, which spans the closed and occluded conformations of the enzyme. Analysis of the molecular dynamics trajectories provides insight into the conformational changes occurring between these two states and the resulting changes in classical electrostatics and specific hydrogen-bonding interactions. The electric fields along the CN axes of the probes are decomposed into contributions from specific residues, ligands, and solvent molecules that make up the microenvironments around the probes. Moreover, calculation of the electric field along the hydride donor-acceptor axis, along with decomposition of this field into specific contributions, indicates that the cofactor and substrate, as well as the enzyme, impose a substantial electric field that facilitates hydride transfer. Overall, experimental and theoretical data provide evidence for significant electrostatic changes in the active site microenvironments due to conformational motion occurring over the catalytic cycle of ecDHFR.

Probing the Electrostatics of Active Site Microenvironments along the Catalytic Cycle for Escherichia coli Dihydrofolate Reductase

PubMed Central

2015-01-01

Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site. The electrostatics and degree of hydration of the microenvironments surrounding the probes are investigated with spectroscopic techniques and mixed quantum mechanical/molecular mechanical (QM/MM) calculations. Changes in the electrostatic microenvironments along the catalytic environment lead to different nitrile (CN) vibrational stretching frequencies and 13C NMR chemical shifts. These environmental changes arise from protein conformational rearrangements during catalysis. The QM/MM calculations reproduce the experimentally measured vibrational frequency shifts of the thiocyanate probes across the catalyzed hydride transfer step, which spans the closed and occluded conformations of the enzyme. Analysis of the molecular dynamics trajectories provides insight into the conformational changes occurring between these two states and the resulting changes in classical electrostatics and specific hydrogen-bonding interactions. The electric fields along the CN axes of the probes are decomposed into contributions from specific residues, ligands, and solvent molecules that make up the microenvironments around the probes. Moreover, calculation of the electric field along the hydride donor–acceptor axis, along with decomposition of this field into specific contributions, indicates that the cofactor and substrate, as well as the enzyme, impose a substantial electric field that facilitates hydride transfer. Overall, experimental and theoretical data provide evidence for significant electrostatic changes in the active site microenvironments due to conformational motion occurring over the catalytic cycle of ecDHFR. PMID:24977791

EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

NASA Astrophysics Data System (ADS)

Weinelt, Martin; von Oppen, Felix

2012-10-01

In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on metal surfaces, focusing on electronic and vibrational spectroscopy in one case and scanning tunneling microscopy studies in the other. Original research articles describe results in many aspects of the field, including: Self-assembly, self-organization, and controlled growth of molecular layers on various substrates. Highly-ordered arrays provide model systems with extraordinary structural properties, allowing one to adjust interactions between molecules and between molecule and substrate, and can be robustly prepared from solution, an essential prerequisite for applications. Conformational or electronic switching of molecules adsorbed at metal and semiconductor surfaces. These studies highlight the elementary processes governing molecular switching at surfaces as well as the wide range of possible stimuli. Carbon-based substrates such as graphene or carbon nanotubes. These substrates are attractive due to their effective two-dimensionality which implies that switching of adsorbed molecules can effect a significant back-action on the substrate. Mechanisms of conformational switching. Several contributions study the role of electron-vibron coupling and heating in current-induced conformational switching. We hope that the collection of articles presented here will stimulate and encourage researchers in surface physics and interfacial chemistry to contribute to the still emerging field of molecular switches at surfaces. We wish to acknowledge the support and input from many colleagues in preparing this special section. A significant part of this work has been conducted in the framework of the Sonderforschungsbereich 658 Elementary Processes in Molecular Switches at Surfaces of the Deutsche Forschungsgemeinschaft, to which we are grateful for financial support. Molecular surfaces at switches contents Molecular switches at surfacesMartin Weinelt and Felix von Oppen Optically and thermally induced molecular switching processes at metal surfacesPetra Tegeder Effects of electron-vibration coupling in transport through single moleculesKatharina J Franke and Jose Ignacio Pascual Vibrational heating in single-molecule switches: an energy-dependent density-of-states approachT Brumme, R Gutierrez and G Cuniberti Reversible switching of single tin phthalocyanine molecules on the InAs(111)A surfaceC Nacci, K Kanisawa and S Fölsch Tuning the interaction between carbon nanotubes and dipole switches: the influence of the change of the nanotube-spiropyran distanceP Bluemmel, A Setaro, C Maity, S Hecht and S Reich Carbon nanotubes as substrates for molecular spiropyran-based switchesE Malic, A Setaro, P Bluemmel, Carlos F Sanz-Navarro, Pablo Ordejón, S Reich and A Knorr Ultrafast dynamics of dithienylethenes differently linked to the surface of TiO2 nanoparticlesLars Dworak, Marc Zastrow, Gehad Zeyat, Karola Rück-Braun and Josef Wachtveitl Switching the electronic properties of Co-octaethylporphyrin molecules on oxygen-covered Ni films by NO adsorptionC F Hermanns, M Bernien, A Krüger, J Miguel and W Kuch STM-switching of organic molecules on semiconductor surfaces: an above threshold density matrix model for 1,5 cyclooctadiene on Si(100)K Zenichowski, Ch Nacci, S Fölsch, J Dokić, T Klamroth and P Saalfrank A switch based on self-assembled thymineFatih Kalkan, Michael Mehlhorn and Karina Morgenstern The growth and electronic structure of azobenzene-based functional molecules on layered crystalsJ Iwicki, E Ludwig, J Buck, M Kalläne, F Köhler, R Herges, L Kipp and K Rossnagel Voltage-dependent conductance states of a single-molecule junctionY F Wang, N Néel, J Kröger, H Vázquez, M Brandbyge, B Wang and R Berndt Molecules with multiple switching units on a Au(111) surface: self-organization and single-molecule manipulationJohannes Mielke, Sofia Selvanathan, Maike Peters, Jutta Schwarz, Stefan Hecht and Leonhard Grill Preparing and regulating a bi-stable molecular switch by atomic manipulationS Sakulsermsuk, R E Palmer and P A Sloan Mixed self-assembled monolayers of azobenzene photoswitches with trifluoromethyl and cyano end groupsDaniel Brete, Daniel Przyrembel, Christian Eickhoff, Robert Carley, Wolfgang Freyer, Karsten Reuter, Cornelius Gahl and Martin Weinelt Reversible electron-induced cis-trans isomerization mediated by intermolecular interactionsCh Lotze, Y Luo, M Corso, K J Franke, R Haag and J I Pascual Transport properties of graphene functionalized with molecular switchesNiels Bode, Eros Mariani and Felix von Oppen

Superchiral Light Generation on Degenerate Achiral Surfaces

NASA Astrophysics Data System (ADS)

Vázquez-Guardado, Abraham; Chanda, Debashis

2018-03-01

A novel route of superchiral near-field generation is demonstrated based on geometrically achiral systems supporting degenerate and spatially superimposed plasmonic modes. Such systems generate a single-handed chiral near field with simultaneous zero far-field circular dichroism. The phenomenon is theoretically elucidated with a rotating dipole model, which predicts a uniform single-handed chiral near field that flips handedness solely by reversing the handedness of the source. This property allows detection of pure background free molecular chirality through near-field light-matter interaction, which is experimentally demonstrated in the precise identification of both handedness of a chiral molecule on a single substrate with about four orders of magnitude enhancement in detection sensitivity compared to its conventional volumetric counterpart.

Thermodynamic and Structural Properties of Methanol-Water Solutions Using Non-Additive Interaction Models

PubMed Central

Zhong, Yang; Warren, G. Lee; Patel, Sandeep

2014-01-01

We study bulk structural and thermodynamic properties of methanol-water solutions via molecular dynamics simulations using novel interaction potentials based on the charge equilibration (fluctuating charge) formalism to explicitly account for molecular polarization at the atomic level. The study uses the TIP4P-FQ potential for water-water interactions, and the CHARMM-based (Chemistry at HARvard Molecular Mechanics) fluctuating charge potential for methanol-methanol and methanol-water interactions. In terms of bulk solution properties, we discuss liquid densities, enthalpies of mixing, dielectric constants, self-diffusion constants, as well as structural properties related to local hydrogen bonding structure as manifested in radial distribution functions and cluster analysis. We further explore the electronic response of water and methanol in the differing local environments established by the interaction of each species predominantly with molecules of the other species. The current force field for the alcohol-water interaction performs reasonably well for most properties, with the greatest deviation from experiment observed for the excess mixing enthalpies, which are predicted to be too favorable. This is qualitatively consistent with the overestimation of the methanol-water gas-phase interaction energy for the lowest-energy conformer (methanol as proton donor). Hydration free energies for methanol in TIP4P-FQ water are predicted to be −5.6±0.2 kcal/mole, in respectable agreement with the experimental value of −5.1 kcal/mole. With respect to solution micro-structure, the present cluster analysis suggests that the micro-scale environment for concentrations where select thermodynamic quantities reach extremal values is described by a bi-percolating network structure. PMID:18074339

Quantum dynamics of light-driven chiral molecular motors.

PubMed

Yamaki, Masahiro; Nakayama, Shin-ichiro; Hoki, Kunihito; Kono, Hirohiko; Fujimura, Yuichi

2009-03-21

The results of theoretical studies on quantum dynamics of light-driven molecular motors with internal rotation are presented. Characteristic features of chiral motors driven by a non-helical, linearly polarized electric field of light are explained on the basis of symmetry argument. The rotational potential of the chiral motor is characterized by a ratchet form. The asymmetric potential determines the directional motion: the rotational direction is toward the gentle slope of the asymmetric potential. This direction is called the intuitive direction. To confirm the unidirectional rotational motion, results of quantum dynamical calculations of randomly-oriented molecular motors are presented. A theoretical design of the smallest light-driven molecular machine is presented. The smallest chiral molecular machine has an optically driven engine and a running propeller on its body. The mechanisms of transmission of driving forces from the engine to the propeller are elucidated by using a quantum dynamical treatment. The results provide a principle for control of optically-driven molecular bevel gears. Temperature effects are discussed using the density operator formalism. An effective method for ultrafast control of rotational motions in any desired direction is presented with the help of a quantum control theory. In this method, visible or UV light pulses are applied to drive the motor via an electronic excited state. A method for driving a large molecular motor consisting of an aromatic hydrocarbon is presented. The molecular motor is operated by interactions between the induced dipole of the molecular motor and the electric field of light pulses.

Molecular Modeling of Nucleic Acid Structure: Electrostatics and Solvation

PubMed Central

Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E.

2014-01-01

This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand the structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as means to sample conformational space for a better understanding of the relevance of a given model. From this discussion, the major limitations with modeling, in general, were highlighted. These are the difficult issues in sampling conformational space effectively—the multiple minima or conformational sampling problems—and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These are discussed in detail in this unit. PMID:18428877

Molecular modeling of nucleic Acid structure: electrostatics and solvation.

PubMed

Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

2014-12-19

This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit. Copyright © 2014 John Wiley & Sons, Inc.

Polymer-dielectric molecular interactions in defect-free poly(3-hexylthiophene): dependence and consequences of regioregularity on transistor charge transport properties

NASA Astrophysics Data System (ADS)

Nawaz, Ali; Cruz-Cruz, Isidro; Rego, Jessica S.; Koehler, Marlus; Gopinathan, Sreelekha P.; Kumar, Anil; Hümmelgen, Ivo A.

2017-08-01

We investigate the molecular interaction of poly(3-hexylthiophene-2,5-diyl) (P3HT) molecules with polar functional groups of the dielectric surface, and its dependence on the regioregularity of P3HT. With this aim, we consider thickness-dependent molecular order of 100% regioregular defect-free P3HT (DF-P3HT) and 93% regioregular P3HT (LT-P3HT), deposited on top of cross-linked poly(vinyl alcohol) (cr-PVA) substrates. Intimate contact of P3HT molecules and cr-PVA surface defects affects the molecular order of P3HT differently, depending on the regioregularity. Consequently, these molecular order changes on the charge transport properties of organic field-effect transistors (OFETs) are investigated using four thicknesses (20, 40, 80 and 120 nm) of P3HT. As compared to other thicknesses, μ sat for 20 nm DF-P3HT OFETs shows further improvement, while the opposite occurs for 20 nm LT-P3HT OFETs. Depending on the regioregularity (and thus the chain orientation), P3HT molecules exhibit a difference in dipole moments. Consequently, the interaction of edge-on or face-on P3HT molecules with cr-PVA surface dipoles has different contributions towards the electrostatic energetic disorder at cr-PVA/P3HT interface. This subtle difference of behavior helps one to understand the huge spread of characteristics of P3HT based transistors found in literature.

Development of concepts on the interaction of drugs with opioid receptors

NASA Astrophysics Data System (ADS)

Kuzmina, N. E.; Kuzmin, V. S.

2011-02-01

The development of concepts on the molecular mechanisms of the action of medicinal drugs on the opioid receptors is briefly surveyed. The modern point of view on the mechanism of activation of opioid receptors is given based on the data from chimeric and site-directed mutagenesis of the cloned opioid receptors and the computer-aided simulations of the reception zone and ligand-receptor complexes. Three-dimensional models of the opioid pharmacophore derived by both conventional methods and a comparative analysis of molecular fields are described in detail.

Modeling hole transport in wet and dry DNA.

PubMed

Pavanello, Michele; Adamowicz, Ludwik; Volobuyev, Maksym; Mennucci, Benedetta

2010-04-08

We present a DFT/classical molecular dynamics model of DNA charge conductivity. The model involves a temperature-driven, hole-hopping charge transfer and includes the time-dependent nonequilibrium interaction of DNA with its molecular environment. We validate our method against a variety of hole transport experiments. The method predicts a significant hole-transfer slowdown of approximately 35% from dry to wet DNA with and without electric field bias. In addition, in agreement with experiments, it also predicts an insulating behavior of (GC)(N) oligomers for 40 < N < 1000, depending on the experimental setup.

The interaction of the outflow with the molecular disk in the Active Galactic Nucleus of NGC 6951

NASA Astrophysics Data System (ADS)

May, D.; Steiner, J. E.; Ricci, T. V.; Menezes, R. B.; Andrade, I. S.

2015-02-01

Context: we present a study of the central 200 pc of NGC 6951, in the optical and NIR, taken with the Gemini North Telescope integral field spectrographs, with resolution of ~ 0''.1 Methods: we used a set of image processing techniques, as the filtering of high spatial and spectral frequencies, Richardson-Lucy deconvolution and PCA Tomography (Steiner et al. 2009) to map the distribution and kinematics of the emission lines. Results: we found a thick molecular disk, with the ionization cone highly misaligned.

Statistics of wormlike chains. II. Phase transition of polymer liquid crystals and its mixture with low molecular weight liquid crystals

NASA Astrophysics Data System (ADS)

Zhang, W. X.; Zhao, S. R.; Sun, C. P.

1997-02-01

A general self-consistent field (SCF) for the mixture of polymer and low molecular weight (LMW) molecules has been derived by variation principle. Considering a Maier-Saupe type of interaction, the analytical expressions of the SCF for polymer liquid crystals (PLCs) and the mixture of PLCs and LMW liquid crystals are obtained, from which the phase behaviors of PLCs as well as the mixture are studied. The theoretical results are in agreement with experimental results by adjusting a parameter.

Comprehensive structure-selective characterization of dissolved organic matter by reducing molecular complexity and increasing analytical dimensions.

PubMed

Li, Yan; Harir, Mourad; Lucio, Marianna; Gonsior, Michael; Koch, Boris P; Schmitt-Kopplin, Philippe; Hertkorn, Norbert

2016-12-01

Deciphering the molecular codes of dissolved organic matter (DOM) improves our understanding of its role in the global element cycles and its active involvement in ecosystem services. This study demonstrates comprehensive characterization of DOM by an initial polarity-based stepwise solid phase extraction (SPE) with single methanol elution of the cartridges, but separate collection of equal aliquots of eluate. The reduction of molecular complexity in the individual DOM fractions attenuates intermolecular interactions and substantially increases the disposable resolution of any structure selective characterization. Suwannee River DOM (SR DOM) was used to collect five distinct SPE fractions with overall 91% DOC recovery. Optical spectroscopy (UV and fluorescence spectroscopy), high-field Fourier transform ion cyclotron mass spectrometry (FTICR MS) and nuclear magnetic resonance (NMR) spectroscopy showed analogous hierarchical clustering among the five eluates corroborating the robustness of this approach. Two abundant moderately hydrophobic fractions contained most of the SR DOM compounds, with substantial proportions of aliphatics, carboxylic-rich alicyclic molecules, carbohydrates and aromatics. A minor early eluting hydrophilic fraction was highly aliphatic and presented a large diversity of alicyclic carboxylic acids, whereas the two late eluting, minor hydrophobic fractions appeared as a largely defunctionalized mixture of aliphatic molecules. Comparative mass analysis showed that fractionation of SR DOM was governed by multiple molecular interactions depending on O/C ratio, molecular weight and aromaticity. The traditional optical indices SUVA 254 and fluorescence index (FI) indicated the relative aromaticity in agreement with FTICR mass and NMR spectra; the classical fluorescent peaks A and C were observed in all four latter eluates. This versatile approach can be easily expanded to preparative scale under field conditions, and transferred to different DOM sources and SPE conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of General and Tailor Made Force Fields via X-ray Thermal Diffuse Scattering Using Molecular Dynamics and Monte Carlo Simulations of Crystalline Aspirin.

PubMed

Chan, Eric J; Neumann, Marcus A

2018-04-10

We have performed a comparison of the experimental thermal diffuse scattering (TDS) from crystalline Aspirin (form I) to that calculated from molecular dynamics (MD) simulations based on a variety of general force fields and a tailor-made force field (TMFF). A comparison is also made with Monte Carlo (MC) simulations which use a "harmonic network" approach to describe the intermolecular interactions. These comparisons were based on the hypothesis that TDS could be a useful experimental data in validation of such simulation parameter sets, especially when calculations of dynamical properties (e.g., thermodynamic free energies) from molecular crystals are concerned. Currently such a validation of force field parameters against experimental data is often limited to calculation of specific physical properties, e.g., absolute lattice energies usually at 0 K or heat capacity measurements. TDS harvested from in-house or synchrotron experiments comprises highly detailed structural information representative of the dynamical motions of the crystal lattice. Thus, TDS is a well-suited experimental data-driven means of cross validating theoretical approaches targeted at understanding dynamical properties of crystals. We found from the results of our investigation that the TMFF and COMPASS (from the commercial software "Materials Studio") parameter sets gave the best agreement with experiment. From our homologous MC simulation analysis we are able to show that force constants associated with the molecular torsion angles are likely to be a strong contributing factor for the apparent reason why these aforementioned force fields performed better.

Dust Processing in Supernova Remnants: Spitzer MIPS SED and IRS Observations

NASA Technical Reports Server (NTRS)

Hewitt, John W.; Petre, Robert; Katsuda Satoru; Andersen, M.; Rho, J.; Reach, W. T.; Bernard, J. P.

2011-01-01

We present Spitzer MIPS SED and IRS observations of 14 Galactic Supernova Remnants previously identified in the GLIMPSE survey. We find evidence for SNR/molecular cloud interaction through detection of [OI] emission, ionic lines, and emission from molecular hydrogen. Through black-body fitting of the MIPS SEDs we find the large grains to be warm, 29-66 K. The dust emission is modeled using the DUSTEM code and a three component dust model composed of populations of big grains, very small grains, and polycyclic aromatic hydrocarbons. We find the dust to be moderately heated, typically by 30-100 times the interstellar radiation field. The source of the radiation is likely hydrogen recombination, where the excitation of hydrogen occurred in the shock front. The ratio of very small grains to big grains is found for most of the molecular interacting SNRs to be higher than that found in the plane of the Milky Way, typically by a factor of 2--3. We suggest that dust shattering is responsible for the relative over-abundance of small grains, in agreement with prediction from dust destruction models. However, two of the SNRs are best fit with a very low abundance of carbon grains to silicate grains and with a very high radiation field. A likely reason for the low abundance of small carbon grains is sputtering. We find evidence for silicate emission at 20 $\\mu$m in their SEDs, indicating that they are young SNRs based on the strong radiation field necessary to reproduce the observed SEDs.

Three-dimensional structure-activity relationship modeling of cocaine binding to two monoclonal antibodies by comparative molecular field analysis.

PubMed

Paula, Stefan; Tabet, Michael R; Keenan, Susan M; Welsh, William J; Ball, W James

2003-01-17

Successful immunotherapy of cocaine addiction and overdoses requires cocaine-binding antibodies with specific properties, such as high affinity and selectivity for cocaine. We have determined the affinities of two cocaine-binding murine monoclonal antibodies (mAb: clones 3P1A6 and MM0240PA) for cocaine and its metabolites by [3H]-radioligand binding assays. mAb 3P1A6 (K(d) = 0.22 nM) displayed a 50-fold higher affinity for cocaine than mAb MM0240PA (K(d) = 11 nM) and also had a greater specificity for cocaine. For the systematic exploration of both antibodies' binding specificities, we used a set of approximately 35 cocaine analogues as structural probes by determining their relative binding affinities (RBAs) using an enzyme-linked immunosorbent competition assay. Three-dimensional quantitative structure-activity relationship (3D-QSAR) models on the basis of comparative molecular field analysis (CoMFA) techniques correlated the binding data with structural features of the ligands. The analysis indicated that despite the mAbs' differing specificities for cocaine, the relative contributions of the steric (approximately 80%) and electrostatic (approximately 20%) field interactions to ligand-binding were similar. Generated three-dimensional CoMFA contour plots then located the specific regions about cocaine where the ligand/receptor interactions occurred. While the overall binding patterns of the two mAbs had many features in common, distinct differences were observed about the phenyl ring and the methylester group of cocaine. Furthermore, using previously published data, a 3D-QSAR model was developed for cocaine binding to the dopamine reuptake transporter (DAT) that was compared to the mAb models. Although the relative steric and electrostatic field contributions were similar to those of the mAbs, the DAT cocaine-binding site showed a preference for negatively charged ligands. Besides establishing molecular level insight into the interactions that govern cocaine binding specificity by biopolymers, the three-dimensional images obtained reflect the properties of the mAbs binding pockets and provide the initial information needed for the possible design of novel antibodies with properties optimized for immunotherapy. Copyright 2003 Elsevier Science Ltd.

Fungal Innate Immunity Induced by Bacterial Microbe-Associated Molecular Patterns (MAMPs)

PubMed Central

Ipcho, Simon; Sundelin, Thomas; Erbs, Gitte; Kistler, H. Corby; Newman, Mari-Anne; Olsson, Stefan

2016-01-01

Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal–bacterial interaction at the molecular level is still in its infancy and little is known about MAMPs and their detection by fungi. Exposing Fusarium graminearum to bacterial MAMPs led to increased fungal membrane hyperpolarization, a putative defense response, and a range of transcriptional responses. The fungus reacted with a different transcript profile to each of the three tested MAMPs, although a core set of genes related to energy generation, transport, amino acid production, secondary metabolism, and especially iron uptake were detected for all three. Half of the genes related to iron uptake were predicted MirA type transporters that potentially take up bacterial siderophores. These quick responses can be viewed as a preparation for further interactions with beneficial or pathogenic bacteria, and constitute a fungal innate immune response with similarities to those of plants and animals. PMID:27172188

vmdICE: a plug-in for rapid evaluation of molecular dynamics simulations using VMD.

PubMed

Knapp, Bernhard; Lederer, Nadja; Omasits, Ulrich; Schreiner, Wolfgang

2010-12-01

Molecular dynamics (MD) is a powerful in silico method to investigate the interactions between biomolecules. It solves Newton's equations of motion for atoms over a specified period of time and yields a trajectory file, containing the different spatial arrangements of atoms during the simulation. The movements and energies of each single atom are recorded. For evaluating of these simulation trajectories with regard to biomedical implications, several methods are available. Three well-known ones are the root mean square deviation (RMSD), the root mean square fluctuation (RMSF) and solvent accessible surface area (SASA). Herein, we present a novel plug-in for the software "visual molecular dynamics" (VMD) that allows an interactive 3D representation of RMSD, RMSF, and SASA, directly on the molecule. On the one hand, our plug-in is easy to handle for inexperienced users, and on the other hand, it provides a fast and flexible graphical impression of the spatial dynamics of a system for experts in the field. © 2010 Wiley Periodicals, Inc.

Optical properties of azobenzene-functionalized self-assembled monolayers: Intermolecular coupling and many-body interactions

NASA Astrophysics Data System (ADS)

Cocchi, Caterina; Moldt, Thomas; Gahl, Cornelius; Weinelt, Martin; Draxl, Claudia

2016-12-01

In a joint theoretical and experimental work, the optical properties of azobenzene-functionalized self-assembled monolayers (SAMs) are studied at different molecular packing densities. Our results, based on density-functional and many-body perturbation theory, as well as on differential reflectance (DR) spectroscopy, shed light on the microscopic mechanisms ruling photo-absorption in these systems. While the optical excitations are intrinsically excitonic in nature, regardless of the molecular concentration, in densely packed SAMs intermolecular coupling and local-field effects are responsible for a sizable weakening of the exciton binding strength. Through a detailed analysis of the character of the electron-hole pairs, we show that distinct excitations involved in the photo-isomerization at low molecular concentrations are dramatically broadened by intermolecular interactions. Spectral shifts in the calculated DR spectra are in good agreement with the experimental results. Our findings represent an important step forward to rationalize the excited-state properties of these complex materials.

Design principles for high–pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hölzl, Christoph; Horinek, Dominik, E-mail: dominik.horinek@ur.de; Kibies, Patrick

Accurate force fields are one of the major pillars on which successful molecular dynamics simulations of complex biomolecular processes rest. They have been optimized for ambient conditions, whereas high-pressure simulations become increasingly important in pressure perturbation studies, using pressure as an independent thermodynamic variable. Here, we explore the design of non-polarizable force fields tailored to work well in the realm of kilobar pressures – while avoiding complete reparameterization. Our key is to first compute the pressure-induced electronic and structural response of a solute by combining an integral equation approach to include pressure effects on solvent structure with a quantum-chemical treatmentmore » of the solute within the embedded cluster reference interaction site model (EC-RISM) framework. Next, the solute’s response to compression is taken into account by introducing pressure-dependence into selected parameters of a well-established force field. In our proof-of-principle study, the full machinery is applied to N,N,N-trimethylamine-N-oxide (TMAO) in water being a potent osmolyte that counteracts pressure denaturation. EC-RISM theory is shown to describe well the charge redistribution upon compression of TMAO(aq) to 10 kbar, which is then embodied in force field molecular dynamics by pressure-dependent partial charges. The performance of the high pressure force field is assessed by comparing to experimental and ab initio molecular dynamics data. Beyond its broad usefulness for designing non-polarizable force fields for extreme thermodynamic conditions, a good description of the pressure-response of solutions is highly recommended when constructing and validating polarizable force fields.« less

Design principles for high-pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures.

PubMed

Hölzl, Christoph; Kibies, Patrick; Imoto, Sho; Frach, Roland; Suladze, Saba; Winter, Roland; Marx, Dominik; Horinek, Dominik; Kast, Stefan M

2016-04-14

Accurate force fields are one of the major pillars on which successful molecular dynamics simulations of complex biomolecular processes rest. They have been optimized for ambient conditions, whereas high-pressure simulations become increasingly important in pressure perturbation studies, using pressure as an independent thermodynamic variable. Here, we explore the design of non-polarizable force fields tailored to work well in the realm of kilobar pressures--while avoiding complete reparameterization. Our key is to first compute the pressure-induced electronic and structural response of a solute by combining an integral equation approach to include pressure effects on solvent structure with a quantum-chemical treatment of the solute within the embedded cluster reference interaction site model (EC-RISM) framework. Next, the solute's response to compression is taken into account by introducing pressure-dependence into selected parameters of a well-established force field. In our proof-of-principle study, the full machinery is applied to N,N,N-trimethylamine-N-oxide (TMAO) in water being a potent osmolyte that counteracts pressure denaturation. EC-RISM theory is shown to describe well the charge redistribution upon compression of TMAO(aq) to 10 kbar, which is then embodied in force field molecular dynamics by pressure-dependent partial charges. The performance of the high pressure force field is assessed by comparing to experimental and ab initio molecular dynamics data. Beyond its broad usefulness for designing non-polarizable force fields for extreme thermodynamic conditions, a good description of the pressure-response of solutions is highly recommended when constructing and validating polarizable force fields.

New diagnostic methods for laser plasma- and microwave-enhanced combustion

PubMed Central

Miles, Richard B; Michael, James B; Limbach, Christopher M; McGuire, Sean D; Chng, Tat Loon; Edwards, Matthew R; DeLuca, Nicholas J; Shneider, Mikhail N; Dogariu, Arthur

2015-01-01

The study of pulsed laser- and microwave-induced plasma interactions with atmospheric and higher pressure combusting gases requires rapid diagnostic methods that are capable of determining the mechanisms by which these interactions are taking place. New rapid diagnostics are presented here extending the capabilities of Rayleigh and Thomson scattering and resonance-enhanced multi-photon ionization (REMPI) detection and introducing femtosecond laser-induced velocity and temperature profile imaging. Spectrally filtered Rayleigh scattering provides a method for the planar imaging of temperature fields for constant pressure interactions and line imaging of velocity, temperature and density profiles. Depolarization of Rayleigh scattering provides a measure of the dissociation fraction, and multi-wavelength line imaging enables the separation of Thomson scattering from Rayleigh scattering. Radar REMPI takes advantage of high-frequency microwave scattering from the region of laser-selected species ionization to extend REMPI to atmospheric pressures and implement it as a stand-off detection method for atomic and molecular species in combusting environments. Femtosecond laser electronic excitation tagging (FLEET) generates highly excited molecular species and dissociation through the focal zone of the laser. The prompt fluorescence from excited molecular species yields temperature profiles, and the delayed fluorescence from recombining atomic fragments yields velocity profiles. PMID:26170432

Mechanism of metamifop inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in Echinochloa crus-galli

NASA Astrophysics Data System (ADS)

Xia, Xiangdong; Tang, Wenjie; He, Shun; Kang, Jing; Ma, Hongju; Li, Jianhong

2016-09-01

Acetyl-coenzyme A carboxylase (ACCase) plays crucial roles in fatty acid metabolism and is an attractive target for herbicide discovery. Metamifop is a novel ACCase-inhibiting herbicide that can be applied to control sensitive weeds in paddy fields. In this study, the effects of metamifop on the chloroplasts, ACCase activity and carboxyltransferase (CT) domain gene expression in Echinochloa crus-galli were investigated. The results showed that metamifop interacted with the CT domain of ACCase in E. crus-galli. The three-dimensional structure of the CT domain of E. crus-galli ACCase in complex with metamifop was examined by homology modelling, molecular docking and molecular dynamics (MD) simulations. Metamifop has a different mechanism of inhibiting the CT domain compared with other ACCase inhibitors as it interacted with a different region in the active site of the CT domain. The protonation of nitrogen in the oxazole ring of metamifop plays a crucial role in the interaction between metamifop and the CT domain. The binding mode of metamifop provides a foundation for elucidating the molecular mechanism of target resistance and cross-resistance among ACCase herbicides, and for designing and optimizing ACCase inhibitors.

Mesoscale computational studies of membrane bilayer remodeling by curvature-inducing proteins

PubMed Central

Ramakrishnan, N.; Sunil Kumar, P. B.; Radhakrishnan, Ravi

2014-01-01

Biological membranes constitute boundaries of cells and cell organelles. These membranes are soft fluid interfaces whose thermodynamic states are dictated by bending moduli, induced curvature fields, and thermal fluctuations. Recently, there has been a flood of experimental evidence highlighting active roles for these structures in many cellular processes ranging from trafficking of cargo to cell motility. It is believed that the local membrane curvature, which is continuously altered due to its interactions with myriad proteins and other macromolecules attached to its surface, holds the key to the emergent functionality in these cellular processes. Mechanisms at the atomic scale are dictated by protein-lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi apparatus. Mapping the relation between the protein-induced deformations at the molecular scale and the resulting mesoscale morphologies is key to bridging cellular experiments across the various length scales. In this review, we focus on the theoretical and computational methods used to understand the phenomenology underlying protein-driven membrane remodeling. Interactions at the molecular scale can be computationally probed by all atom and coarse grained molecular dynamics (MD, CGMD), as well as dissipative particle dynamics (DPD) simulations, which we only describe in passing. We choose to focus on several continuum approaches extending the Canham - Helfrich elastic energy model for membranes to include the effect of curvature-inducing proteins and explore the conformational phase space of such systems. In this description, the protein is expressed in the form of a spontaneous curvature field. The approaches include field theoretical methods limited to the small deformation regime, triangulated surfaces and particle-based computational models to investigate the large-deformation regimes observed in the natural state of many biological membranes. Applications of these methods to understand the properties of biological membranes in homogeneous and inhomogeneous environments of proteins, whose underlying curvature fields are either isotropic or anisotropic, are discussed. The diversity in the curvature fields elicits a rich variety of morphological states, including tubes, discs, branched tubes, and caveola. Mapping the thermodynamic stability of these states as a function of tuning parameters such as concentration and strength of curvature induction of the proteins is discussed. The relative stabilities of these self-organized shapes are examined through free-energy calculations. The suite of methods discussed here can be tailored to applications in specific cellular settings such as endocytosis during cargo trafficking and tubulation of filopodial structures in migrating cells, which makes these methods a powerful complement to experimental studies. PMID:25484487

Mesoscale computational studies of membrane bilayer remodeling by curvature-inducing proteins.

PubMed

Ramakrishnan, N; Sunil Kumar, P B; Radhakrishnan, Ravi

2014-10-01

Biological membranes constitute boundaries of cells and cell organelles. These membranes are soft fluid interfaces whose thermodynamic states are dictated by bending moduli, induced curvature fields, and thermal fluctuations. Recently, there has been a flood of experimental evidence highlighting active roles for these structures in many cellular processes ranging from trafficking of cargo to cell motility. It is believed that the local membrane curvature, which is continuously altered due to its interactions with myriad proteins and other macromolecules attached to its surface, holds the key to the emergent functionality in these cellular processes. Mechanisms at the atomic scale are dictated by protein-lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi apparatus. Mapping the relation between the protein-induced deformations at the molecular scale and the resulting mesoscale morphologies is key to bridging cellular experiments across the various length scales. In this review, we focus on the theoretical and computational methods used to understand the phenomenology underlying protein-driven membrane remodeling. Interactions at the molecular scale can be computationally probed by all atom and coarse grained molecular dynamics (MD, CGMD), as well as dissipative particle dynamics (DPD) simulations, which we only describe in passing. We choose to focus on several continuum approaches extending the Canham - Helfrich elastic energy model for membranes to include the effect of curvature-inducing proteins and explore the conformational phase space of such systems. In this description, the protein is expressed in the form of a spontaneous curvature field. The approaches include field theoretical methods limited to the small deformation regime, triangulated surfaces and particle-based computational models to investigate the large-deformation regimes observed in the natural state of many biological membranes. Applications of these methods to understand the properties of biological membranes in homogeneous and inhomogeneous environments of proteins, whose underlying curvature fields are either isotropic or anisotropic, are discussed. The diversity in the curvature fields elicits a rich variety of morphological states, including tubes, discs, branched tubes, and caveola. Mapping the thermodynamic stability of these states as a function of tuning parameters such as concentration and strength of curvature induction of the proteins is discussed. The relative stabilities of these self-organized shapes are examined through free-energy calculations. The suite of methods discussed here can be tailored to applications in specific cellular settings such as endocytosis during cargo trafficking and tubulation of filopodial structures in migrating cells, which makes these methods a powerful complement to experimental studies.

Mesoscale computational studies of membrane bilayer remodeling by curvature-inducing proteins

NASA Astrophysics Data System (ADS)

Ramakrishnan, N.; Sunil Kumar, P. B.; Radhakrishnan, Ravi

2014-10-01

Biological membranes constitute boundaries of cells and cell organelles. These membranes are soft fluid interfaces whose thermodynamic states are dictated by bending moduli, induced curvature fields, and thermal fluctuations. Recently, there has been a flood of experimental evidence highlighting active roles for these structures in many cellular processes ranging from trafficking of cargo to cell motility. It is believed that the local membrane curvature, which is continuously altered due to its interactions with myriad proteins and other macromolecules attached to its surface, holds the key to the emergent functionality in these cellular processes. Mechanisms at the atomic scale are dictated by protein-lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi apparatus. Mapping the relation between the protein-induced deformations at the molecular scale and the resulting mesoscale morphologies is key to bridging cellular experiments across various length scales. In this review, we focus on the theoretical and computational methods used to understand the phenomenology underlying protein-driven membrane remodeling. Interactions at the molecular scale can be computationally probed by all atom and coarse grained molecular dynamics (MD, CGMD), as well as dissipative particle dynamics (DPD) simulations, which we only describe in passing. We choose to focus on several continuum approaches extending the Canham-Helfrich elastic energy model for membranes to include the effect of curvature-inducing proteins and explore the conformational phase space of such systems. In this description, the protein is expressed in the form of a spontaneous curvature field. The approaches include field theoretical methods limited to the small deformation regime, triangulated surfaces and particle-based computational models to investigate the large-deformation regimes observed in the natural state of many biological membranes. Applications of these methods to understand the properties of biological membranes in homogeneous and inhomogeneous environments of proteins, whose underlying curvature fields are either isotropic or anisotropic, are discussed. The diversity in the curvature fields elicits a rich variety of morphological states, including tubes, discs, branched tubes, and caveola. Mapping the thermodynamic stability of these states as a function of tuning parameters such as concentration and strength of curvature induction of the proteins is discussed. The relative stabilities of these self-organized shapes are examined through free-energy calculations. The suite of methods discussed here can be tailored to applications in specific cellular settings such as endocytosis during cargo trafficking and tubulation of filopodial structures in migrating cells, which makes these methods a powerful complement to experimental studies.

Design of novel quinazolinone derivatives as inhibitors for 5HT7 receptor.

PubMed

Chitta, Aparna; Jatavath, Mohan Babu; Fatima, Sabiha; Manga, Vijjulatha

2012-02-01

To study the pharmacophore properties of quinazolinone derivatives as 5HT(7) inhibitors, 3D QSAR methodologies, namely Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were applied, partial least square (PLS) analysis was performed and QSAR models were generated. The derived model showed good statistical reliability in terms of predicting the 5HT(7) inhibitory activity of the quinazolione derivative, based on molecular property fields like steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields. This is evident from statistical parameters like q(2) (cross validated correlation coefficient) of 0.642, 0.602 and r(2) (conventional correlation coefficient) of 0.937, 0.908 for CoMFA and CoMSIA respectively. The predictive ability of the models to determine 5HT(7) antagonistic activity is validated using a test set of 26 molecules that were not included in the training set and the predictive r(2) obtained for the test set was 0.512 & 0.541. Further, the results of the derived model are illustrated by means of contour maps, which give an insight into the interaction of the drug with the receptor. The molecular fields so obtained served as the basis for the design of twenty new ligands. In addition, ADME (Adsorption, Distribution, Metabolism and Elimination) have been calculated in order to predict the relevant pharmaceutical properties, and the results are in conformity with required drug like properties.

Advanced Mass Spectrometry Technologies for the Study of Microbial Pathogenesis

PubMed Central

Moore, Jessica L.; Caprioli, Richard M.; Skaar, Eric P.

2014-01-01

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been successfully applied to the field of microbial pathogenesis with promising results, principally in diagnostic microbiology to rapidly identify bacteria based on the molecular profiles of small cell populations. Direct profiling of molecules from serum and tissue samples by MALDI MS providesa means to study the pathogen-host interaction and to discover potential markers of infection. Systematic molecular profiling across tissue sections represents a new imaging modality, enabling regiospecific molecular measurements to be made in situ, in both two- and three-dimensional analyses. Herein, we briefly summarize work that employs MALDI MS to study the pathogenesis of microbial infection. PMID:24997399

Electrostatically Tuned Self-Assembly of Branched Amphiphilic Peptides

DOE PAGES

Ting, Christina L.; Frischknecht, Amalie L.; Stevens, Mark J.; ...

2014-06-19

Electrostatics plays an important role in the self-assembly of amphiphilic peptides. To develop a molecular understanding of the role of the electrostatic interactions, we develop a coarse-grained model peptide and apply self-consistent field theory to investigate the peptide assembly into a variety of aggregate nanostructures. We find that the presence and distribution of charged groups on the hydrophilic branches of the peptide can modify the molecular configuration from extended to collapsed. This change in molecular configuration influences the packing into spherical micelles, cylindrical micelles (nanofibers), or planar bilayers. The effects of charge distribution therefore has important implications for the designmore » and utility of functional materials based on peptides.« less

Uncovering Specific Electrostatic Interactions in the Denatured States of Proteins

PubMed Central

Shen, Jana K.

2010-01-01

The stability and folding of proteins are modulated by energetically significant interactions in the denatured state that is in equilibrium with the native state. These interactions remain largely invisible to current experimental techniques, however, due to the sparse population and conformational heterogeneity of the denatured-state ensemble under folding conditions. Molecular dynamics simulations using physics-based force fields can in principle offer atomistic details of the denatured state. However, practical applications are plagued with the lack of rigorous means to validate microscopic information and deficiencies in force fields and solvent models. This study presents a method based on coupled titration and molecular dynamics sampling of the denatured state starting from the extended sequence under native conditions. The resulting denatured-state pKas allow for the prediction of experimental observables such as pH- and mutation-induced stability changes. I show the capability and use of the method by investigating the electrostatic interactions in the denatured states of wild-type and K12M mutant of NTL9 protein. This study shows that the major errors in electrostatics can be identified by validating the titration properties of the fragment peptides derived from the sequence of the intact protein. Consistent with experimental evidence, our simulations show a significantly depressed pKa for Asp8 in the denatured state of wild-type, which is due to a nonnative interaction between Asp8 and Lys12. Interestingly, the simulation also shows a nonnative interaction between Asp8 and Glu48 in the denatured state of the mutant. I believe the presented method is general and can be applied to extract and validate microscopic electrostatics of the entire folding energy landscape. PMID:20682271

Rational design of novel, fluorescent, tagged glutamic acid dendrimers with different terminal groups and in silico analysis of their properties

PubMed Central

Martinho, Nuno; Silva, Liana C; Florindo, Helena F; Brocchini, Steve; Zloh, Mire; Barata, Teresa S

2017-01-01

Dendrimers are hyperbranched polymers with a multifunctional architecture that can be tailored for the use in various biomedical applications. Peptide dendrimers are particularly relevant for drug delivery applications due to their versatility and safety profile. The overall lack of knowledge of their three-dimensional structure, conformational behavior and structure–activity relationship has slowed down their development. Fluorophores are often conjugated to dendrimers to study their interaction with biomolecules and provide information about their mechanism of action at the molecular level. However, these probes can change dendrimer surface properties and have a direct impact on their interactions with biomolecules and with lipid membranes. In this study, we have used computer-aided molecular design and molecular dynamics simulations to identify optimal topology of a poly(l-glutamic acid) (PG) backbone dendrimer that allows incorporation of fluorophores in the core with minimal availability for undesired interactions. Extensive all-atom molecular dynamic simulations with the CHARMM force field were carried out for different generations of PG dendrimers with the core modified with a fluorophore (nitrobenzoxadiazole and Oregon Green 488) and various surface groups (glutamic acid, lysine and tryptophan). Analysis of structural and topological features of all designed dendrimers provided information about their size, shape, internal distribution and dynamic behavior. We have found that four generations of a PG dendrimer are needed to ensure minimal exposure of a core-conjugated fluorophore to external environment and absence of undesired interactions regardless of the surface terminal groups. Our findings suggest that NBD-PG-G4 can provide a suitable scaffold to be used for biophysical studies of surface-modified dendrimers to provide a deeper understanding of their intermolecular interactions, mechanisms of action and trafficking in a biological system. PMID:29026301

Rational design of novel, fluorescent, tagged glutamic acid dendrimers with different terminal groups and in silico analysis of their properties.

PubMed

Martinho, Nuno; Silva, Liana C; Florindo, Helena F; Brocchini, Steve; Zloh, Mire; Barata, Teresa S

2017-01-01

Dendrimers are hyperbranched polymers with a multifunctional architecture that can be tailored for the use in various biomedical applications. Peptide dendrimers are particularly relevant for drug delivery applications due to their versatility and safety profile. The overall lack of knowledge of their three-dimensional structure, conformational behavior and structure-activity relationship has slowed down their development. Fluorophores are often conjugated to dendrimers to study their interaction with biomolecules and provide information about their mechanism of action at the molecular level. However, these probes can change dendrimer surface properties and have a direct impact on their interactions with biomolecules and with lipid membranes. In this study, we have used computer-aided molecular design and molecular dynamics simulations to identify optimal topology of a poly(l-glutamic acid) (PG) backbone dendrimer that allows incorporation of fluorophores in the core with minimal availability for undesired interactions. Extensive all-atom molecular dynamic simulations with the CHARMM force field were carried out for different generations of PG dendrimers with the core modified with a fluorophore (nitrobenzoxadiazole and Oregon Green 488) and various surface groups (glutamic acid, lysine and tryptophan). Analysis of structural and topological features of all designed dendrimers provided information about their size, shape, internal distribution and dynamic behavior. We have found that four generations of a PG dendrimer are needed to ensure minimal exposure of a core-conjugated fluorophore to external environment and absence of undesired interactions regardless of the surface terminal groups. Our findings suggest that NBD-PG-G4 can provide a suitable scaffold to be used for biophysical studies of surface-modified dendrimers to provide a deeper understanding of their intermolecular interactions, mechanisms of action and trafficking in a biological system.

Quantum chemical methods for the investigation of photoinitiated processes in biological systems: theory and applications.

PubMed

Dreuw, Andreas

2006-11-13

With the advent of modern computers and advances in the development of efficient quantum chemical computer codes, the meaningful computation of large molecular systems at a quantum mechanical level became feasible. Recent experimental effort to understand photoinitiated processes in biological systems, for instance photosynthesis or vision, at a molecular level also triggered theoretical investigations in this field. In this Minireview, standard quantum chemical methods are presented that are applicable and recently used for the calculation of excited states of photoinitiated processes in biological molecular systems. These methods comprise configuration interaction singles, the complete active space self-consistent field method, and time-dependent density functional theory and its variants. Semiempirical approaches are also covered. Their basic theoretical concepts and mathematical equations are briefly outlined, and their properties and limitations are discussed. Recent successful applications of the methods to photoinitiated processes in biological systems are described and theoretical tools for the analysis of excited states are presented.

The binding domain of the HMGB1 inhibitor carbenoxolone: Theory and experiment

NASA Astrophysics Data System (ADS)

Mollica, Luca; Curioni, Alessandro; Andreoni, Wanda; Bianchi, Marco E.; Musco, Giovanna

2008-05-01

We present a combined computational and experimental study of the interaction of the Box A of the HMGB1 protein and carbenoxolone, an inhibitor of its pro-inflammatory activity. The computational approach consists of classical molecular dynamics (MD) simulations based on the GROMOS force field with quantum-refined (QRFF) atomic charges for the ligand. Experimental data consist of fluorescence intensities, chemical shift displacements, saturation transfer differences and intermolecular Nuclear Overhauser Enhancement signals. Good agreement is found between observations and the conformation of the ligand-protein complex resulting from QRFF-MD. In contrast, simple docking procedures and MD based on the unrefined force field provide models inconsistent with experiment. The ligand-protein binding is dominated by non-directional interactions.

Control of Screening of a Charged Particle in Electrolytic Aqueous Paul Trap

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jae Hyun nmn; Krstic, Predrag S

2011-01-01

Individual charged particles could be trapped and confined in the combined radio-frequency and DC quadrupole electric field of an aqueous Paul trap. Viscosity of water improves confinement and extends the range of the trap parameters which characterize the stability of the trap. Electrolyte, if present in aqueous solution, may screen the charged particle and thus partially or fully suppress electrophoretic interaction with the applied filed, possibly reducing it to a generally much weaker dielectrophoretic interaction with an induced dipole. Applying molecular dynamics simulation we show that the quadrupole field has a different affects at the electrolyte ions and at muchmore » heavier charged particle, effectively eliminating the screening effect and reinstating the electrophoretic confinement.« less

Control Of Screening Of A Charged Particle In Electrolytic Aqueous Paul Trap

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jae Hyun; Krstic, Predrag S.

2011-06-01

Individual charged particles could be trapped and confined by the combined radio-frequency and DC quadrupole electric field of an aqueous Paul trap. Viscosity of water improves confinement and extends the range of the trap parameters which characterize the stability of the trap. Electrolyte, if present in aqueous solution, may screen the charged particle and thus partially or fully suppress electrophoretic interaction with the applied filed, possibly reducing it to a generally much weaker dielectrophoretic interaction with an induced dipole. Applying molecular dynamics simulation we show that the quadrupole field has a different effect at the electrolyte ions and at muchmore » heavier charged particle, effectively eliminating the screening by electrolyte ions and reinstating the electrophoretic confinement.« less

Spectroscopically determined force field for water dimer: physically enhanced treatment of hydrogen bonding in molecular mechanics energy functions.

PubMed

Mannfors, Berit; Palmo, Kim; Krimm, Samuel

2008-12-11

Our ab initio transformed spectroscopically determined force field (SDFF) methodology emphasizes, in addition to accurate structure and energy performance, comparable prediction of vibrational properties in order to improve reproduction of interaction forces. It is now applied to the determination of a molecular mechanics (MM) force field for the water monomer and dimer as an initial step in developing a more physically based treatment of the hydrogen bonding that not only underlies condensed-phase water but also must be important in molecular-level protein-water interactions. Essential electrical components of the SDFF for monomer water are found to be the following: an off-plane charge distribution, this distribution consisting of four off-atom charge sites in traditional lone pair (LP) but also in inverted lone pair (ILP) positions; allowance for a diffuse size to these off-atom sites; and the incorporation of charge fluxes (i.e., the change in charge with change in internal coordinate). Parametrization of such an LP/ILP model together with the SDFF analytically transformed valence force field results in essentially exact agreement with ab initio (in this case MP2/6-31++G(d,p)) structure, electrical, and vibrational properties. Although we demonstrate that the properties of this monomer electrical model together with its van der Waals and polarization interactions are transferable to the dimer, this is not sufficient in reproducing comparable dimer properties, most notably the huge increase in infrared intensity of a donor OH stretch mode. This deficiency, which can be eliminated by a large dipole-derivative-determined change in the effective charge flux of the donor hydrogen-bonded OH bond, is not accounted for by the charge flux change in this bond due to the induction effects of the acceptor electric field alone, and can only be fully removed by an added bond flux associated with the extent of overlap of the wave functions of the two molecules. We show that this overlap charge flux (OCF) emulates an actual O-H...LP-O intermolecular dipole flux, reflecting the unitary nature of the hydrogen-bonded system in the context of MM-separable molecules. The effectiveness of incorporating the OCF noncanonical character demonstrates that a distinctively QM-unique property can be substantively represented in MM energy functions.

Practical quantum mechanics-based fragment methods for predicting molecular crystal properties.

PubMed

Wen, Shuhao; Nanda, Kaushik; Huang, Yuanhang; Beran, Gregory J O

2012-06-07

Significant advances in fragment-based electronic structure methods have created a real alternative to force-field and density functional techniques in condensed-phase problems such as molecular crystals. This perspective article highlights some of the important challenges in modeling molecular crystals and discusses techniques for addressing them. First, we survey recent developments in fragment-based methods for molecular crystals. Second, we use examples from our own recent research on a fragment-based QM/MM method, the hybrid many-body interaction (HMBI) model, to analyze the physical requirements for a practical and effective molecular crystal model chemistry. We demonstrate that it is possible to predict molecular crystal lattice energies to within a couple kJ mol(-1) and lattice parameters to within a few percent in small-molecule crystals. Fragment methods provide a systematically improvable approach to making predictions in the condensed phase, which is critical to making robust predictions regarding the subtle energy differences found in molecular crystals.

Thermodynamic Characterization of Hydration Sites from Integral Equation-Derived Free Energy Densities: Application to Protein Binding Sites and Ligand Series.

PubMed

Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Lionta, Evanthia; Heil, Jochen; Kast, Stefan M

2017-07-24

Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design. Unlike molecular dynamics-based approaches, 3D RISM theory allows for fast and noise-free calculations using the same detailed level of solute-solvent interaction description. Here we correlate molecular water entities instead of mere site density maxima with local contributions to the solvation free energy using novel algorithms. Distinct water molecules and hydration sites are investigated in multiple protein-ligand X-ray structures, namely streptavidin, factor Xa, and factor VIIa, based on 3D RISM-derived free energy density fields. Our approach allows the semiquantitative assessment of whether a given structural water molecule can potentially be targeted for replacement in structure-based design. Finally, PLS-based regression models from free energy density fields used within a 3D-QSAR approach (CARMa - comparative analysis of 3D RISM Maps) are shown to be able to extract relevant information for the interpretation of structure-activity relationship (SAR) trends, as demonstrated for a series of serine protease inhibitors.

Prospects of nanoparticle-DNA binding and its implications in medical biotechnology.

PubMed

An, Hongjie; Jin, Bo

2012-01-01

Bio-nanotechnology is a new interdisciplinary R&D area that integrates engineering and physical science with biology through the development of multifunctional devices and systems, focusing biology inspired processes or their applications, in particular in medical biotechnology. DNA based nanotechnology, in many ways, has been one of the most intensively studied fields in recent years that involves the use and the creation of bio-inspired materials and their technologies for highly selective biosensing, nanoarchitecture engineering and nanoelectronics. Increasing researches have been offered to a fundamental understanding how the interactions between the nanoparticles and DNA molecules could alter DNA molecular structure and its biochemical activities. This minor review describes the mechanisms of the nanoparticle-DNA binding and molecular interactions. We present recent discoveries and research progresses how the nanoparticle-DNA binding could vary DNA molecular structure, DNA detection, and gene therapy. We report a few case studies associated with the application of the nanoparticle-DNA binding devices in medical detection and biotechnology. The potential impacts of the nanoparticles via DNA binding on toxicity of the microorganisms are briefly discussed. The nanoparticle-DNA interactions and their impact on molecular and microbial functionalities have only drown attention in recent a few years. The information presented in this review can provide useful references for further studies on biomedical science and technology. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling molecule-plasmon interactions using quantized radiation fields within time-dependent electronic structure theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nascimento, Daniel R.; DePrince, A. Eugene, E-mail: deprince@chem.fsu.edu

2015-12-07

We present a combined cavity quantum electrodynamics/ab initio electronic structure approach for simulating plasmon-molecule interactions in the time domain. The simple Jaynes-Cummings-type model Hamiltonian typically utilized in such simulations is replaced with one in which the molecular component of the coupled system is treated in a fully ab initio way, resulting in a computationally efficient description of general plasmon-molecule interactions. Mutual polarization effects are easily incorporated within a standard ground-state Hartree-Fock computation, and time-dependent simulations carry the same formal computational scaling as real-time time-dependent Hartree-Fock theory. As a proof of principle, we apply this generalized method to the emergence ofmore » a Fano-like resonance in coupled molecule-plasmon systems; this feature is quite sensitive to the nanoparticle-molecule separation and the orientation of the molecule relative to the polarization of the external electric field.« less

Resolution-Adapted All-Atomic and Coarse-Grained Model for Biomolecular Simulations.

PubMed

Shen, Lin; Hu, Hao

2014-06-10

We develop here an adaptive multiresolution method for the simulation of complex heterogeneous systems such as the protein molecules. The target molecular system is described with the atomistic structure while maintaining concurrently a mapping to the coarse-grained models. The theoretical model, or force field, used to describe the interactions between two sites is automatically adjusted in the simulation processes according to the interaction distance/strength. Therefore, all-atomic, coarse-grained, or mixed all-atomic and coarse-grained models would be used together to describe the interactions between a group of atoms and its surroundings. Because the choice of theory is made on the force field level while the sampling is always carried out in the atomic space, the new adaptive method preserves naturally the atomic structure and thermodynamic properties of the entire system throughout the simulation processes. The new method will be very useful in many biomolecular simulations where atomistic details are critically needed.

Energy and structure of bonds in the interaction of organic anions with layered double hydroxide nanosheets: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Tsukanov, A. A.; Psakhie, S. G.

2016-01-01

The application of hybrid and hierarchical nanomaterials based on layered hydroxides and oxyhydroxides of metals is a swiftly progressing field in biomedicine. Layered double hydroxides (LDH) possess a large specific surface area, significant surface electric charge and biocompatibility. Their physical and structural properties enable them to adsorb various kinds of anionic species and to transport them into cells. However, possible side effects resulting from the interaction of LDH with anions of the intercellular and intracellular medium need to be considered, since such interaction can potentially disrupt ion transport, signaling processes, apoptosis, nutrition and proliferation of living cells. In the present paper molecular dynamics is used to determine the energies of interaction of organic anions (aspartic acid, glutamic acid and bicarbonate) with a fragment of layered double hydroxide Mg/Al-LDH. The average number of hydrogen bonds between the anions and the hydroxide surface and characteristic binding configurations are determined. Possible effects of LDH on the cell resulting from binding of protein fragments and replacement of native intracellular anions with delivered anions are considered.

Protein-Carbohydrate Interactions Studied by NMR: From Molecular Recognition to Drug Design

PubMed Central

Fernández-Alonso, María del Carmen; Díaz, Dolores; Berbis, Manuel Álvaro; Marcelo, Filipa; Cañada, Javier; Jiménez-Barbero, Jesús

2012-01-01

Diseases that result from infection are, in general, a consequence of specific interactions between a pathogenic organism and the cells. The study of host-pathogen interactions has provided insights for the design of drugs with therapeutic properties. One area that has proved to be promising for such studies is the constituted by carbohydrates which participate in biological processes of paramount importance. On the one hand, carbohydrates have shown to be information carriers with similar, if not higher, importance than traditionally considered carriers as amino acids and nucleic acids. On the other hand, the knowledge on molecular recognition of sugars by lectins and other carbohydrate-binding proteins has been employed for the development of new biomedical strategies. Biophysical techniques such as X-Ray crystallography and NMR spectroscopy lead currently the investigation on this field. In this review, a description of traditional and novel NMR methodologies employed in the study of sugar-protein interactions is briefly presented in combination with a palette of NMR-based studies related to biologically and/or pharmaceutically relevant applications. PMID:23305367

Dependence of Interaction Free Energy between Solutes on an External Electrostatic Field

PubMed Central

Yang, Pei-Kun

2013-01-01

To explore the athermal effect of an external electrostatic field on the stabilities of protein conformations and the binding affinities of protein-protein/ligand interactions, the dependences of the polar and hydrophobic interactions on the external electrostatic field, −Eext, were studied using molecular dynamics (MD) simulations. By decomposing Eext into, along, and perpendicular to the direction formed by the two solutes, the effect of Eext on the interactions between these two solutes can be estimated based on the effects from these two components. Eext was applied along the direction of the electric dipole formed by two solutes with opposite charges. The attractive interaction free energy between these two solutes decreased for solutes treated as point charges. In contrast, the attractive interaction free energy between these two solutes increased, as observed by MD simulations, for Eext = 40 or 60 MV/cm. Eext was applied perpendicular to the direction of the electric dipole formed by these two solutes. The attractive interaction free energy was increased for Eext = 100 MV/cm as a result of dielectric saturation. The force on the solutes along the direction of Eext computed from MD simulations was greater than that estimated from a continuum solvent in which the solutes were treated as point charges. To explore the hydrophobic interactions, Eext was applied to a water cluster containing two neutral solutes. The repulsive force between these solutes was decreased/increased for Eext along/perpendicular to the direction of the electric dipole formed by these two solutes. PMID:23852018

Polarizable Multipole-Based Force Field for Dimethyl and Trimethyl Phosphate

PubMed Central

2015-01-01

Phosphate groups are commonly observed in biomolecules such as nucleic acids and lipids. Due to their highly charged and polarizable nature, modeling these compounds with classical force fields is challenging. Using quantum mechanical studies and liquid-phase simulations, the AMOEBA force field for dimethyl phosphate (DMP) ion and trimethyl phosphate (TMP) has been developed. On the basis of ab initio calculations, it was found that ion binding and the solution environment significantly impact both the molecular geometry and the energy differences between conformations. Atomic multipole moments are derived from MP2/cc-pVQZ calculations of methyl phosphates at several conformations with their chemical environments taken into account. Many-body polarization is handled via a Thole-style induction model using distributed atomic polarizabilities. van der Waals parameters of phosphate and oxygen atoms are determined by fitting to the quantum mechanical interaction energy curves for water with DMP or TMP. Additional stretch-torsion and angle-torsion coupling terms were introduced in order to capture asymmetry in P–O bond lengths and angles due to the generalized anomeric effect. The resulting force field for DMP and TMP is able to accurately describe both the molecular structure and conformational energy surface, including bond and angle variations with conformation, as well as interaction of both species with water and metal ions. The force field was further validated for TMP in the condensed phase by computing hydration free energy, liquid density, and heat of vaporization. The polarization behavior between liquid TMP and TMP in water is drastically different. PMID:26574325

Surface-directed molecular assembly of pentacene on monolayer graphene for high-performance organic transistors.

PubMed

Lee, Wi Hyoung; Park, Jaesung; Sim, Sung Hyun; Lim, Soojin; Kim, Kwang S; Hong, Byung Hee; Cho, Kilwon

2011-03-30

Organic electronic devices that use graphene electrodes have received considerable attention because graphene is regarded as an ideal candidate electrode material. Transfer and lithographic processes during fabrication of patterned graphene electrodes typically leave polymer residues on the graphene surfaces. However, the impact of these residues on the organic semiconductor growth mechanism on graphene surface has not been reported yet. Here, we demonstrate that polymer residues remaining on graphene surfaces induce a stand-up orientation of pentacene, thereby controlling pentacene growth such that the molecular assembly is optimal for charge transport. Thus, pentacene field-effect transistors (FETs) using source/drain monolayer graphene electrodes with polymer residues show a high field-effect mobility of 1.2 cm(2)/V s. In contrast, epitaxial growth of pentacene having molecular assembly of lying-down structure is facilitated by π-π interaction between pentacene and the clean graphene electrode without polymer residues, which adversely affects lateral charge transport at the interface between electrode and channel. Our studies provide that the obtained high field-effect mobility in pentacene FETs using monolayer graphene electrodes arises from the extrinsic effects of polymer residues as well as the intrinsic characteristics of the highly conductive, ultrathin two-dimensional monolayer graphene electrodes.

Force-field parametrization and molecular dynamics simulations of Congo red

NASA Astrophysics Data System (ADS)

Król, Marcin; Borowski, Tomasz; Roterman, Irena; Piekarska, Barbara; Stopa, Barbara; Rybarska, Joanna; Konieczny, Leszek

2004-01-01

Congo red, a diazo dye widely used in medical diagnosis, is known to form supramolecular systems in solution. Such a supramolecular system may interact with various proteins. In order to examine the nature of such complexes empirical force field parameters for the Congo red molecule were developed. The parametrization of bonding terms closely followed the methodology used in the development of the charmm22 force field, except for the calculation of charges. Point charges were calculated from a fit to a quantum mechanically derived electrostatic potential using the CHELP-BOW method. Obtained parameters were tested in a series of molecular dynamics simulations of both a single molecule and a micelle composed of Congo red molecules. It is shown that newly developed parameters define a stable minimum on the hypersurface of the potential energy and crystal and ab initio geometries and rotational barriers are well reproduced. Furthermore, rotations around C-N bonds are similar to torsional vibrations observed in crystals of diphenyl-diazene, which confirms that the flexibility of the molecule is correct. Comparison of results obtained from micelles molecular dynamics simulations with experimental data shows that the thermal dependence of micelle creation is well reproduced.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zwier, Timothy S.

The Gordon Research Conference on ATOMIC & MOLECULAR INTERACTIONS was held at Stonehill College Easton, Massachusetts, July 15-20, 2012. The Conference was well-attended with 121 participants (attendees list attached). The attendees represented the spectrum of endeavor in this field coming from academia, industry, and government laboratories, both U.S. and foreign scientists, senior researchers, young investigators, and students. Of the 121 attendees, 64 voluntarily responded to a general inquiry regarding ethnicity which appears on our registration forms. Of the 64 respondents, 11% were Minorities – 2% Hispanic, 9% Asian and 0% African American. Approximately 20% of the participants at the 2012more » meeting were women. The Gordon Research SEMINAR on ATOMIC & MOLECULAR INTERACTIONS was held at Stonehill College Easton, Massachusetts, July 14 - 15, 2012. The Conference was well-attended with 42 participants (attendees list attached). The attendees represented the spectrum of endeavor in this field coming from academia, industry, and government laboratories, both U.S. and foreign scientists, senior researchers, young investigators, and students. Of the 42 attendees, 20 voluntarily responded to a general inquiry regarding ethnicity which appears on our registration forms. Of the 20 respondents, 10% were Minorities – 0% Hispanic, 10% Asian and 0% African American. Approximately 29% of the participants at the 2012 meeting were women. In designing the formal speakers program, emphasis was placed on current unpublished research and discussion of the future target areas in this field. There was a conscious effort to stimulate lively discussion about the key issues in the field today. Time for formal presentations was limited in the interest of group discussions. In order that more scientists could communicate their most recent results, poster presentation time was scheduled. Attached is a copy of the formal schedule and speaker program and the poster program. In addition to these formal interactions, "free time" was scheduled to allow informal discussions. Such discussions are fostering new collaborations and joint efforts in the field.« less

Toward self-organization and complex matter.

PubMed

Lehn, Jean-Marie

2002-03-29

Beyond molecular chemistry based on the covalent bond, supramolecular chemistry aims at developing highly complex chemical systems from components interacting through noncovalent intermolecular forces. Over the past quarter century, supramolecular chemistry has grown into a major field and has fueled numerous developments at the interfaces with biology and physics. Some of the conceptual advances and future challenges are profiled here.

Learning Systems Biology: Conceptual Considerations toward a Web-Based Learning Platform

ERIC Educational Resources Information Center

Emmert-Streib, Frank; Dehmer, Matthias; Lyardet, Fernando

2013-01-01

Within recent years, there is an increasing need to train students, from biology and beyond, in quantitative methods that are relevant to cope with data-driven biology. Systems Biology is such a field that places a particular focus on the functional aspect of biology and molecular interacting processes. This paper deals with the conceptual design…

Device considerations for development of conductance-based biosensors

PubMed Central

Lee, Kangho; Nair, Pradeep R.; Scott, Adina; Alam, Muhammad A.; Janes, David B.

2009-01-01

Design and fabrication of electronic biosensors based on field-effect-transistor (FET) devices require understanding of interactions between semiconductor surfaces and organic biomolecules. From this perspective, we review practical considerations for electronic biosensors with emphasis on molecular passivation effects on FET device characteristics upon immobilization of organic molecules and an electrostatic model for FET-based biosensors. PMID:24753627

Techniques for Investigating Molecular Toxicology of Nanomaterials.

PubMed

Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong

2016-06-01

Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods.

Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

PubMed

Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

2017-05-01

In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Divalent Ion Parameterization Strongly Affects Conformation and Interactions of an Anionic Biomimetic Polymer.

PubMed

Daily, Michael D; Baer, Marcel D; Mundy, Christopher J

2016-03-10

The description of peptides and the use of molecular dynamics simulations to refine structures and investigate the dynamics on an atomistic scale are well developed. Through a consensus in this community over multiple decades, parameters were developed for molecular interactions that only require the sequence of amino-acids and an initial guess for the three-dimensional structure. The recent discovery of peptoids will require a retooling of the currently available interaction potentials in order to have the same level of confidence in the predicted structures and pathways as there is presently in the peptide counterparts. Here we present modeling of peptoids using a combination of ab initio molecular dynamics (AIMD) and atomistic resolution classical force field (FF) to span the relevant time and length scales. To properly account for the dominant forces that stabilize ordered structures of peptoids, namely steric-, electrostatic, and hydrophobic interactions mediated through side chain-side chain interactions in the FF model, those have to be first mapped out using high fidelity atomistic representations. A key feature here is not only to use gas phase quantum chemistry tools, but also account for solvation effects in the condensed phase through AIMD. One major challenge is to elucidate ion binding to charged or polar regions of the peptoid and its concomitant role in the creation of local order. Here, similar to proteins, a specific ion effect is observed suggesting that both the net charge and the precise chemical nature of the ion will need to be described.

Monitoring adsorption of gold nanoparticles on gold nanodisk array using dark-field hyperspectral microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Fusheng; Zenasni, Oussama; Li, Jingting; Shih, Wei-Chuan

2017-02-01

Localized surface plasmon resonance (LSPR) arises from the interaction of light with noble metal nanoparticles, which induces a collective oscillation in the free electrons. The size and shape of the metallic nanostructure significantly impact LSPR frequency and strength. Nanoplasmonic sensor has become a recent research focus due to its significant signal enhancement and robust signal transduction measured by extinction spectroscopy, fluorescence, Raman scattering, and absorption spectroscopy. Dark-field microscopy, in contrast, reports the scattered photons after light-matter interactions. In this case, the nanoparticles can be understood as dipole radiators whose free electrons oscillate in concert. Coupled with spectroscopy, this platform allows the collection of plasmonically scattered spectra from gold nanoparticles. Plasmonic coupling between electron-beam lithography patterned gold nanodisks (AuND) and colloidal gold nanoparticles (AuNP) can change the plasmonic resonance of the original entities, and can be effectively studied by dark-field hyperspectral microscopy. Typically, a pronounced redshift can be observed when plasmonic coupling occurs. When these nano-entities are functionalized with interactive surface moieties, biochemistry and molecular processes can be studied. In this paper, we will present the capability of assessing the process of immobilizing streptavidin-functionalized AuNPs on an array of biotin-terminated AuNDs. By monitoring changes in the LSPR band of AuNDs, we are able to evaluate similar processes in other molecular systems. In addition, plasmon coupling induced scattering intensity variations can be measured by an electron-multiplied charge-coupled device camera for rapid in situ monitoring. This method can potentially be useful in studying dynamic biophysical and biochemical processes in situ.

All-Atom MD Simulation of DNA Condensation Using Ab Initio Derived Force Field Parameters of Cobalt(III)-Hexammine.

PubMed

Sun, Tiedong; Mirzoev, Alexander; Korolev, Nikolay; Lyubartsev, Alexander P; Nordenskiöld, Lars

2017-08-24

It is well established that the presence of the trivalent cobalt(III)-hexammine cation (CoHex 3+ ) at submillimolar concentrations leads to bundling (condensation) of double-stranded DNA molecules, which is caused by DNA-DNA attraction induced by the multivalent counterions. However, the detailed mechanism of this process is still not fully understood. Furthermore, in all-atom molecular dynamics (MD) simulations, spontaneous aggregation of several DNA oligonucleotides in the presence of CoHex 3+ has previously not been demonstrated. In order to obtain a rigorous description of CoHex 3+ -nucleic acid interactions and CoHex 3+ -induced DNA condensation to be used in MD simulations, we have derived optimized force field parameters of the CoHex 3+ ion. They were obtained from Car-Parrinello molecular dynamics simulation of a single CoHex 3+ ion in the presence of 125 water molecules. The new set of force field parameters reproduces the experimentally known transition of DNA from B- to A-form, and qualitatively describes changes of DNA and RNA persistence lengths. We then carried out a 2 μs long atomistic simulation of four DNA oligomers each consisting of 36 base pairs in the presence of CoHex 3+ . We demonstrate that, in this system, DNA molecules display attractive interactions and aggregate into bundle-like structures. This behavior depends critically on the details of the CoHex 3+ interaction with DNA. A control simulation with a similar setup but in the presence of Mg 2+ does not induce DNA-DNA attraction, which is also in agreement with experiment.

The chemistry side of AOP: implications for toxicity ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) is a structured representation of the biological events that lead to adverse impacts following a molecular initiating event caused by chemical interaction with a macromolecule. AOPs have been proposed to facilitate toxicity extrapolation across species through understanding of species similarity in the sequence of molecular, cellular, organ and organismal level responses. However, AOPs are non-specific regarding the identity of the chemical initiators, and the range of structures for which an AOP is considered applicable has generally been poorly defined. Applicability domain has been widely understood in the field of QSAR as the response and chemical structure space in which the model makes predictions with a given reliability, and has been traditionally applied to define the similarity of query molecules within the training set. Three dimensional (3D) receptor modeling offers an approach to better define the applicability domain for selected AOPs through determination of the chemical space of the molecular initiating event. Universal 3D-QSAR models were developed for acetylcholinesterase inhibitors and estrogen receptor agonists and antagonists using a combination of fingerprint, molecular docking and structure-based pharmacophore approaches. The models were based on the critical molecular interactions within each receptor ligand binding domain, and included the key amino acid residues responsible for high binding affinity. T

Molecularly Imprinted Intelligent Scaffolds for Tissue Engineering Applications.

PubMed

Neves, Mariana I; Wechsler, Marissa E; Gomes, Manuela E; Reis, Rui L; Granja, Pedro L; Peppas, Nicholas A

2017-02-01

The development of molecularly imprinted polymers (MIPs) using biocompatible production methods enables the possibility to further exploit this technology for biomedical applications. Tissue engineering (TE) approaches use the knowledge of the wound healing process to design scaffolds capable of modulating cell behavior and promote tissue regeneration. Biomacromolecules bear great interest for TE, together with the established recognition of the extracellular matrix, as an important source of signals to cells, both promoting cell-cell and cell-matrix interactions during the healing process. This review focuses on exploring the potential of protein molecular imprinting to create bioactive scaffolds with molecular recognition for TE applications based on the most recent approaches in the field of molecular imprinting of macromolecules. Considerations regarding essential components of molecular imprinting technology will be addressed for TE purposes. Molecular imprinting of biocompatible hydrogels, namely based on natural polymers, is also reviewed here. Hydrogel scaffolds with molecular memory show great promise for regenerative therapies. The first molecular imprinting studies analyzing cell adhesion report promising results with potential applications for cell culture systems, or biomaterials for implantation with the capability for cell recruitment by selectively adsorbing desired molecules.

Mechanisms of relaxation and spin decoherence in nanomagnets

NASA Astrophysics Data System (ADS)

van Tol, Johan

Relaxation in spin systems is of great interest with respect to various possible applications like quantum information processing and storage, spintronics, and dynamic nuclear polarization (DNP). The implementation of high frequencies and fields is crucial in the study of systems with large zero-field splitting or large interactions, as for example molecular magnets and low dimensional magnetic materials. Here we will focus on the implementation of pulsed Electron Paramagnetic Resonance (ERP) at multiple frequencies of 10, 95, 120, 240, and 336 GHz, and the relaxation and decoherence processes as a function of magnetic field and temperature. Firstly, at higher frequencies the direct single-phonon spin-lattice relaxation (SLR) is considerably enhanced, and will more often than not be the dominant relaxation mechanism at low temperatures, and can be much faster than at lower fields and frequencies. In principle the measurement of the SLR rates as a function of the frequency provides a means to map the phonon density of states. Secondly, the high electron spin polarization at high fields has a strong influence on the spin fluctuations in relatively concentrated spin systems, and the contribution of the electron-electron dipolar interactions to the coherence rate can be partially quenched at low temperatures. This not only allows the study of relatively concentrated spin systems by pulsed EPR (as for example magnetic nanoparticles and molecular magnets), it enables the separation of the contribution of the fluctuations of the electron spin system from other decoherence mechanisms. Besides choice of temperature and field, several strategies in sample design, pulse sequences, or clock transitions can be employed to extend the coherence time in nanomagnets. A review will be given of the decoherence mechanisms with an attempt at a quantitative comparison of experimental rates with theory.

Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

PubMed

Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

2016-06-20

A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Supramolecular chemistry: from molecular information towards self-organization and complex matter

NASA Astrophysics Data System (ADS)

Lehn, Jean-Marie

2004-03-01

Molecular chemistry has developed a wide range of very powerful procedures for constructing ever more sophisticated molecules from atoms linked by covalent bonds. Beyond molecular chemistry lies supramolecular chemistry, which aims at developing highly complex chemical systems from components interacting via non-covalent intermolecular forces. By the appropriate manipulation of these interactions, supramolecular chemistry became progressively the chemistry of molecular information, involving the storage of information at the molecular level, in the structural features, and its retrieval, transfer, and processing at the supramolecular level, through molecular recognition processes operating via specific interactional algorithms. This has paved the way towards apprehending chemistry also as an information science. Numerous receptors capable of recognizing, i.e. selectively binding, specific substrates have been developed, based on the molecular information stored in the interacting species. Suitably functionalized receptors may perform supramolecular catalysis and selective transport processes. In combination with polymolecular organization, recognition opens ways towards the design of molecular and supramolecular devices based on functional (photoactive, electroactive, ionoactive, etc) components. A step beyond preorganization consists in the design of systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined supramolecular architectures by self-assembly from their components. Self-organization processes, directed by the molecular information stored in the components and read out at the supramolecular level through specific interactions, represent the operation of programmed chemical systems. They have been implemented for the generation of a variety of discrete functional architectures of either organic or inorganic nature. Self-organization processes also give access to advanced supramolecular materials, such as supramolecular polymers and liquid crystals, and provide an original approach to nanoscience and nanotechnology. In particular, the spontaneous but controlled generation of well-defined, functional supramolecular architectures of nanometric size through self-organization represents a means of performing programmed engineering and processing of nanomaterials. Supramolecular chemistry is intrinsically a dynamic chemistry, in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when a molecular entity contains covalent bonds that may form and break reversibly, so as to make possible a continuous change in constitution and structure by reorganization and exchange of building blocks. This behaviour defines a constitutional dynamic chemistry that allows self-organization by selection as well as by design at both the molecular and supramolecular levels. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization by selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation in a Darwinistic fashion. The merging of the features, information and programmability, dynamics and reversibility, constitution and structural diversity, points towards the emergence of adaptative and evolutionary chemistry. Together with the corresponding fields of physics and biology, it constitutes a science of informed matter, of organized, adaptative complex matter. This article was originally published in 2003 by the Israel Academy of Sciences and Humanities in the framework of its Albert Einstein Memorial Lectures series. Reprinted by permission of the Israel Academy of Sciences and Humanities.

Sampling Long- versus Short-Range Interactions Defines the Ability of Force Fields To Reproduce the Dynamics of Intrinsically Disordered Proteins.

PubMed

Mercadante, Davide; Wagner, Johannes A; Aramburu, Iker V; Lemke, Edward A; Gräter, Frauke

2017-09-12

Molecular dynamics (MD) simulations have valuably complemented experiments describing the dynamics of intrinsically disordered proteins (IDPs), particularly since the proposal of models to solve the artificial collapse of IDPs in silico. Such models suggest redefining nonbonded interactions, by either increasing water dispersion forces or adopting the Kirkwood-Buff force field. These approaches yield extended conformers that better comply with experiments, but it is unclear if they all sample the same intrachain dynamics of IDPs. We have tested this by employing MD simulations and single-molecule Förster resonance energy transfer spectroscopy to sample the dimensions of systems with different sequence compositions, namely strong and weak polyelectrolytes. For strong polyelectrolytes in which charge effects dominate, all the proposed solutions equally reproduce the expected ensemble's dimensions. For weak polyelectrolytes, at lower cutoffs, force fields abnormally alter intrachain dynamics, overestimating excluded volume over chain flexibility or reporting no difference between the dynamics of different chains. The TIP4PD water model alone can reproduce experimentally observed changes in extensions (dimensions), but not quantitatively and with only weak statistical significance. Force field limitations are reversed with increased interaction cutoffs, showing that chain dynamics are critically defined by the presence of long-range interactions. Force field analysis aside, our study provides the first insights into how long-range interactions critically define IDP dimensions and raises the question of which length range is crucial to correctly sample the overall dimensions and internal dynamics of the large group of weakly charged yet highly polar IDPs.

Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy.

PubMed

Kedrov, Alexej; Janovjak, Harald; Sapra, K Tanuj; Müller, Daniel J

2007-01-01

Molecular interactions are the basic language of biological processes. They establish the forces interacting between the building blocks of proteins and other macromolecules, thus determining their functional roles. Because molecular interactions trigger virtually every biological process, approaches to decipher their language are needed. Single-molecule force spectroscopy (SMFS) has been used to detect and characterize different types of molecular interactions that occur between and within native membrane proteins. The first experiments detected and localized molecular interactions that stabilized membrane proteins, including how these interactions were established during folding of alpha-helical secondary structure elements into the native protein and how they changed with oligomerization, temperature, and mutations. SMFS also enables investigators to detect and locate molecular interactions established during ligand and inhibitor binding. These exciting applications provide opportunities for studying the molecular forces of life. Further developments will elucidate the origins of molecular interactions encoded in their lifetimes, interaction ranges, interplay, and dynamics characteristic of biological systems.

A Hilly path through the thermodynamics and statistical mechanics of protein solutions.

PubMed

Wills, Peter R

2016-12-01

The opus of Don Winzor in the fields of physical and analytical biochemistry is a major component of that certain antipodean approach to this broad area of research that blossomed in the second half of the twentieth century. The need to formulate problems in terms of thermodynamic nonideality posed the challenge of describing a clear route from molecular interactions to the parameters that biochemists routinely measure. Mapping out this route required delving into the statistical mechanics of solutions of macromolecules, and at every turn mathematically complex, rigorous, general results that had previously been derived previously, often by Terrell Hill, came to the fore. Central to this work were the definition of the "thermodynamic activity", the pivotal position of the polynomial expansion of the osmotic pressure in terms of molar concentration and the relationship of virial coefficients to details of the forces between limited-size groups of interacting molecules. All of this was richly exploited in the task of taking account of excluded volume and electrostatic interactions, especially in the use of sedimentation equilibrium to determine values of constants for molecular association reactions. Such an approach has proved relevant to the study of molecular interactions generally, even those between the main macromolecular solute and components of the solvent, by using techniques such as exclusion and affinity chromatography as well as light scattering.

Ising versus XY anisotropy in frustrated R(2)Ti(2)O(7) compounds as "Seen" by Polarized Neutrons.

PubMed

Cao, H; Gukasov, A; Mirebeau, I; Bonville, P; Decorse, C; Dhalenne, G

2009-07-31

We studied the field induced magnetic order in R(2)Ti(2)O(7) pyrochlore compounds with either uniaxial (R=Ho, Tb) or planar (R=Er, Yb) anisotropy, by polarized neutron diffraction. The determination of the local susceptibility tensor {chi(parallel to),chi(perpendicular)} provides a universal description of the field induced structures in the paramagnetic phase (2-270 K), whatever the field value (1-7 T) and direction. Comparison of the thermal variations of chi(parallel to) and chi(perpendicular) with calculations using the rare earth crystal field shows that exchange and dipolar interactions must be taken into account. We determine the molecular field tensor in each case and show that it can be strongly anisotropic.

Calculation of the flow field in supersonic mixed-compression inlets at angle of attack using the three-dimensional method of characteristics with discrete shock wave fitting

NASA Technical Reports Server (NTRS)

Vadyak, J.; Hoffman, J. D.

1978-01-01

The influence of molecular transport is included in the computation by treating viscous and thermal diffusion terms in the governing partial differential equations as correction terms in the method of characteristics scheme. The development of a production type computer program is reported which is capable of calculating the flow field in a variety of axisymmetric mixed-compression aircraft inlets. The results agreed well with those produced by the two-dimensional method characteristics when axisymmetric flow fields are computed. For three-dimensional flow fields, the results agree well with experimental data except in regions of high viscous interaction and boundary layer removal.

Enhancing coherence in molecular spin qubits via atomic clock transitions

NASA Astrophysics Data System (ADS)

Shiddiq, Muhandis; Komijani, Dorsa; Duan, Yan; Gaita-Ariño, Alejandro; Coronado, Eugenio; Hill, Stephen

2016-03-01

Quantum computing is an emerging area within the information sciences revolving around the concept of quantum bits (qubits). A major obstacle is the extreme fragility of these qubits due to interactions with their environment that destroy their quantumness. This phenomenon, known as decoherence, is of fundamental interest. There are many competing candidates for qubits, including superconducting circuits, quantum optical cavities, ultracold atoms and spin qubits, and each has its strengths and weaknesses. When dealing with spin qubits, the strongest source of decoherence is the magnetic dipolar interaction. To minimize it, spins are typically diluted in a diamagnetic matrix. For example, this dilution can be taken to the extreme of a single phosphorus atom in silicon, whereas in molecular matrices a typical ratio is one magnetic molecule per 10,000 matrix molecules. However, there is a fundamental contradiction between reducing decoherence by dilution and allowing quantum operations via the interaction between spin qubits. To resolve this contradiction, the design and engineering of quantum hardware can benefit from a ‘bottom-up’ approach whereby the electronic structure of magnetic molecules is chemically tailored to give the desired physical behaviour. Here we present a way of enhancing coherence in solid-state molecular spin qubits without resorting to extreme dilution. It is based on the design of molecular structures with crystal field ground states possessing large tunnelling gaps that give rise to optimal operating points, or atomic clock transitions, at which the quantum spin dynamics become protected against dipolar decoherence. This approach is illustrated with a holmium molecular nanomagnet in which long coherence times (up to 8.4 microseconds at 5 kelvin) are obtained at unusually high concentrations. This finding opens new avenues for quantum computing based on molecular spin qubits.

Molecular analysis of Hsp70 mechanisms in plants and their function in response to stress.

PubMed

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

2017-04-01

Studying the strategies of improving abiotic stress tolerance is quite imperative and research under this field will increase our understanding of response mechanisms to abiotic stress such as heat. The Hsp70 is an essential regulator of protein having the tendency to maintain internal cell stability like proper folding protein and breakdown of unfolded proteins. Hsp70 holds together protein substrates to help in movement, regulation, and prevent aggregation under physical and or chemical pressure. However, this review reports the molecular mechanism of heat shock protein 70 kDa (Hsp70) action and its structural and functional analysis, research progress on the interaction of Hsp70 with other proteins and their interaction mechanisms as well as the involvement of Hsp70 in abiotic stress responses as an adaptive defense mechanism.

Molecular docking and dynamics simulations of A.niger RNase from Aspergillus niger ATCC26550: for potential prevention of human cancer.

PubMed

Kumar, Gundampati Ravi; Chikati, Rajasekhar; Pandrangi, Santhi Latha; Kandapal, Manoj; Sonkar, Kirti; Gupta, Neeraj; Mulakayala, Chaitanya; Jagannadham, Medicherla V; Kumar, Chitta Suresh; Saxena, Sunita; Das, Mira Debnath

2013-02-01

The aim of the present research was to study the anticancer effects of Aspergillus niger (A.niger) RNase. We found that RNase (A.niger RNase) significantly and dose dependently inhibited invasiveness of breast cancer cell line MDA MB 231 by 55 % (P<0.01) at 1 μM concentration. At a concentration of 2 μM, the anti invasive effect of the enzyme increased to 90 % (P<0.002). Keeping the aim to determine molecular level interactions (molecular simulations and protein docking) of human actin with A.niger RNase we extended our work in-vitro to in-silico studies. To gain better relaxation and accurate arrangement of atoms, refinement was done on the human actin and A.niger RNase by energy minimization (EM) and molecular dynamics (MD) simulations using 43A(2) force field of Gromacs96 implemented in the Gromacs 4.0.5 package, finally the interaction energies were calculated by protein-protein docking using the HEX. These in vitro and in-silico structural studies prove the effective inhibition of actin activity by A.niger RNase in neoplastic cells and thereby provide new insights for the development of novel anti cancer drugs.

Homology modeling, molecular docking and molecular dynamics studies of the catalytic domain of chitin deacetylase from Cryptococcus laurentii strain RY1.

PubMed

Sarkar, Soumyadev; Gupta, Suchetana; Chakraborty, Writachit; Senapati, Sanjib; Gachhui, Ratan

2017-11-01

This study provides structural insights into chitin deacetylase, over-expressing under nitrogen limiting condition in Cryptococcus laurentii strain RY1. The enzyme converts chitin, the second most abundant natural biopolymer, to chitosan, which offers tremendous applications in diverse fields. To elucidate the structure-function relationship of this biologically and industrially important enzyme, a homology model of the catalytic domain was constructed. The stability of the structure was assessed by molecular dynamics simulation studies. Tryptophan 151 of the domain was identified to form hydrogen bond and stacking interaction with chitin upon docking. In Silico substitution of Tryptophan (W) to Alanine (A), Phenylalanine (F) and Aspartate (D) corroborated the importance of the Tryptophan residue in interaction with the substrate. This is the first report of unravelling the structural characteristics of chitin deacetylase from Cryptococcus and understanding the approach of the enzyme towards its substrate. Our results would be helpful to perform experimental validations and apply quantum mechanics/molecular mechanics techniques to determine the detailed catalytic mechanism and enhance the industrial potency of the enzyme. Copyright © 2017 Elsevier B.V. All rights reserved.

Modelling the interactions between animal venom peptides and membrane proteins.

PubMed

Hung, Andrew; Kuyucak, Serdar; Schroeder, Christina I; Kaas, Quentin

2017-12-01

The active components of animal venoms are mostly peptide toxins, which typically target ion channels and receptors of both the central and peripheral nervous system, interfering with action potential conduction and/or synaptic transmission. The high degree of sequence conservation of their molecular targets makes a range of these toxins active at human receptors. The high selectivity and potency displayed by some of these toxins have prompted their use as pharmacological tools as well as drugs or drug leads. Molecular modelling has played an essential role in increasing our molecular-level understanding of the activity and specificity of animal toxins, as well as engineering them for biotechnological and pharmaceutical applications. This review focuses on the biological insights gained from computational and experimental studies of animal venom toxins interacting with membranes and ion channels. A host of recent X-ray crystallography and electron-microscopy structures of the toxin targets has contributed to a dramatic increase in the accuracy of the molecular models of toxin binding modes greatly advancing this exciting field of study. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Behavior of P85 and P188 Poloxamer Molecules: Computer Simulations Using United Atom Force Field.

DOE PAGES

Goliaei, Ardeshir; Lau, Edmond Y.; Adhikari, Upendra; ...

2016-05-27

To study the interaction between poloxamer molecules and lipid bilayers using molecular dynamics simulation technique with the united atom resolution, we augmented the GROMOS force field to include poloxamers. We validated the force field by calculating the radii of gyration of two poloxamers, P85 and P188, solvated in water and by considering the poloxamer density distributions at the air/water interface. The emphasis of our simulations was on the study of the interaction between poloxamers and lipid bilayer. At the water/lipid bilayer interface, we observed that both poloxamers studied, P85 and P188, behaved like surfactants: the hydrophilic blocks of poloxamers becamemore » adsorbed at the polar interface, while their hydrophobic block penetrated the interface into the aliphatic tail region of the lipid bilayer. We also observed that when P85 and P188 poloxamers interacted with damaged membranes that contained pores, the hydrophobic blocks of copolymers penetrated into the membrane in the vicinity of the pore and compressed the membrane. Lastly, due to this compression, water molecules were evacuated from the pore.« less

Advances in visual representation of molecular potentials.

PubMed

Du, Qi-Shi; Huang, Ri-Bo; Chou, Kuo-Chen

2010-06-01

The recent advances in visual representations of molecular properties in 3D space are summarized, and their applications in molecular modeling study and rational drug design are introduced. The visual representation methods provide us with detailed insights into protein-ligand interactions, and hence can play a major role in elucidating the structure or reactivity of a biomolecular system. Three newly developed computation and visualization methods for studying the physical and chemical properties of molecules are introduced, including their electrostatic potential, lipophilicity potential and excess chemical potential. The newest application examples of visual representations in structure-based rational drug are presented. The 3D electrostatic potentials, calculated using the empirical method (EM-ESP), in which the classical Coulomb equation and traditional atomic partial changes are discarded, are highly consistent with the results by the higher level quantum chemical method. The 3D lipophilicity potentials, computed by the heuristic molecular lipophilicity potential method based on the principles of quantum mechanics and statistical mechanics, are more accurate and reliable than those by using the traditional empirical methods. The 3D excess chemical potentials, derived by the reference interaction site model-hypernetted chain theory, provide a new tool for computational chemistry and molecular modeling. For structure-based drug design, the visual representations of molecular properties will play a significant role in practical applications. It is anticipated that the new advances in computational chemistry will stimulate the development of molecular modeling methods, further enriching the visual representation techniques for rational drug design, as well as other relevant fields in life science.

Ambient ionization mass spectrometry imaging for characterizing plant-microbe interactions using liquid extraction surface analysis (LESA)

NASA Astrophysics Data System (ADS)

Chu, R. K.; Anderton, C.; Weston, D. J.; Carrell, A. A.; Paša-Tolić, L.; Veličković, D.; Tfaily, M.

2017-12-01

The rhizosphere consists of a diverse community of plants, bacteria and fungi that are interacting with each other and with complex soil matrix they occupy. By studying the chemical signaling and processes that occur within this dynamic microenvironment, we will further our understanding of the symbiotic and competitive interaction within microbial communities. Field studies and bulk analyses shed light on the mechanisms by which environmental perturbations alter carbon and nitrogen cycling, but what is less clear are the intra- and interspecies molecular transformations and transactions between the different constituents within the rhizosphere. Chemical imaging by liquid extraction surface analysis mass spectrometry (LESA-MS) is a highly sensitive technique capable of providing both spatial and molecular information. Here, we examined the chemical interactions among a tripartite system of peat moss (Sphagnum fallax), cyanobacteria (Nostoc muscorium), and fungus (Trizdiaspa). We coupled LESA source to both a 15 Tesla Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS), for ultrahigh mass resolution and mass accuracy results, and a Thermo Velos-LTQ mass spectrometer, for tandem MS of selected molecules to increase confidence in molecular identifications. With LESA-MS approach we spatially probed the tripartite interactions and isolated cultures using a coordinate system that can be mapped back and overlaid onto the original image. Using this method, we mapped an array of metabolic distributions within the model sphagnum microbiome. For instance, we identified carbendazim, an anti-fungal agent, distributed within the interaction zone between the bacteria and fungi, while glyceropcholine and sucrose were localized within the sphagnum and fungus interaction zone. Further analysis will look into larger metabolites, lipids, and small proteins.

Workshop on High-Field NMR and Biological Applications

NASA Astrophysics Data System (ADS)

Scientists at the Pacific Northwest Laboratory have been working toward the establishment of a new Molecular Science Research Center (MSRC). The primary scientific thrust of this new research center is in the areas of theoretical chemistry, chemical dynamics, surface and interfacial science, and studies on the structure and interactions of biological macromolecules. The MSRC will provide important new capabilities for studies on the structure of biological macromolecules. The MSRC program includes several types of advanced spectroscopic techniques for molecular structure analysis, and a theory and modeling laboratory for molecular mechanics/dynamics calculations and graphics. It is the goal to closely integrate experimental and theoretical studies on macromolecular structure, and to join these research efforts with those of the molecular biological programs to provide new insights into the structure/function relationships of biological macromolecules. One of the areas of structural biology on which initial efforts in the MSRC will be focused is the application of high field, 2-D NMR to the study of biological macromolecules. First, there is interest in obtaining 3-D structural information on large proteins and oligonucleotides. Second, one of the primary objectives is to closely link theoretical approaches to molecular structure analysis with the results obtained in experimental research using NMR and other spectroscopies.

Model based on GRID-derived descriptors for estimating CYP3A4 enzyme stability of potential drug candidates

NASA Astrophysics Data System (ADS)

Crivori, Patrizia; Zamora, Ismael; Speed, Bill; Orrenius, Christian; Poggesi, Italo

2004-03-01

A number of computational approaches are being proposed for an early optimization of ADME (absorption, distribution, metabolism and excretion) properties to increase the success rate in drug discovery. The present study describes the development of an in silico model able to estimate, from the three-dimensional structure of a molecule, the stability of a compound with respect to the human cytochrome P450 (CYP) 3A4 enzyme activity. Stability data were obtained by measuring the amount of unchanged compound remaining after a standardized incubation with human cDNA-expressed CYP3A4. The computational method transforms the three-dimensional molecular interaction fields (MIFs) generated from the molecular structure into descriptors (VolSurf and Almond procedures). The descriptors were correlated to the experimental metabolic stability classes by a partial least squares discriminant procedure. The model was trained using a set of 1800 compounds from the Pharmacia collection and was validated using two test sets: the first one including 825 compounds from the Pharmacia collection and the second one consisting of 20 known drugs. This model correctly predicted 75% of the first and 85% of the second test set and showed a precision above 86% to correctly select metabolically stable compounds. The model appears a valuable tool in the design of virtual libraries to bias the selection toward more stable compounds. Abbreviations: ADME - absorption, distribution, metabolism and excretion; CYP - cytochrome P450; MIFs - molecular interaction fields; HTS - high throughput screening; DDI - drug-drug interactions; 3D - three-dimensional; PCA - principal components analysis; CPCA - consensus principal components analysis; PLS - partial least squares; PLSD - partial least squares discriminant; GRIND - grid independent descriptors; GRID - software originally created and developed by Professor Peter Goodford.

Circularly polarized attosecond pulse generation and applications to ultrafast magnetism

NASA Astrophysics Data System (ADS)

Bandrauk, André D.; Guo, Jing; Yuan, Kai-Jun

2017-12-01

Attosecond science is a growing new field of research and potential applications which relies on the development of attosecond light sources. Achievements in the generation and application of attosecond pulses enable to investigate electron dynamics in the nonlinear nonperturbative regime of laser-matter interactions on the electron’s natural time scale, the attosecond. In this review, we describe the generation of circularly polarized attosecond pulses and their applications to induce attosecond magnetic fields, new tools for ultrafast magnetism. Simulations are performed on aligned one-electron molecular ions by using nonperturbative nonlinear solutions of the time-dependent Schrödinger equation. We discuss how bichromatic circularly polarized laser pulses with co-rotating or counter-rotating components induce electron-parent ion recollisions, thus producing circularly polarized high-order harmonic generation, the source of circularly polarized attosecond pulses. Ultrafast quantum electron currents created by the generated attosecond pulses give rise to attosecond magnetic field pulses. The results provide a guiding principle for producing circularly polarized attosecond pulses and ultrafast magnetic fields in complex molecular systems for future research in ultrafast magneto-optics.

[Molecular fundamentals of drug interactions in the therapy of colorectal cancer].

PubMed

Regulska, Katarzyna; Stanisz, Beata; Regulski, Miłosz; Gieremek, Paulina

2014-03-04

Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs' pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

Oxidation of Sn doped Cu cluster: A first principle study

NASA Astrophysics Data System (ADS)

Parida, Ganesh; Majumder, Chiranjib

2017-05-01

Bimetallic clusters have immense potential to exhibit tunable properties in the emerging field of nano catalysis. Using plane wave based pseudopotential approach we have investigated the oxidation behavior of pure and Sn doped Cu13 clusters. The results showed significant modification of the cluster geometry upon interaction with oxygen molecule. The interaction of oxygen with Cu13, Cu12Sn1 and Cu11Sn2 clusters show dissociative chemisorption is more favorable than molecular adsorption. In addition, the adsorption energy is found to decrease with the increase in Sn concentration.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Sang D.; Borodin, Oleg; Seo, D. M.

Electrolytes with the salt lithium bis(fluorosulfonyl)imide (LiFSI) have been evaluated relative to comparable electrolytes with other lithium salts. Acetonitrile (AN) has been used as a model electrolyte solvent. The information obtained from the thermal phase behavior, solvation/ionic association interactions, quantum chemical (QC) calculations and molecular dynamics (MD) simulations (with an APPLE&P many-body polarizable force field for the LiFSI salt) of the (AN)n-LiFSI mixtures provides detailed insight into the coordination interactions of the FSI- anions and the wide variability noted in the electrolyte transport property (i.e., viscosity and ionic conductivity).

Circadian Clocks in the Cnidaria: Environmental Entrainment, Molecular Regulation, and Organismal Outputs

PubMed Central

Reitzel, Adam M.; Tarrant, Ann M.; Levy, Oren

2013-01-01

The circadian clock is a molecular network that translates predictable environmental signals, such as light levels, into organismal responses, including behavior and physiology. Regular oscillations of the molecular components of the clock enable individuals to anticipate regularly fluctuating environmental conditions. Cnidarians play important roles in benthic and pelagic marine environments and also occupy a key evolutionary position as the likely sister group to the bilaterians. Together, these attributes make members of this phylum attractive as models for testing hypotheses on roles for circadian clocks in regulating behavior, physiology, and reproduction as well as those regarding the deep evolutionary conservation of circadian regulatory pathways in animal evolution. Here, we review and synthesize the field of cnidarian circadian biology by discussing the diverse effects of daily light cycles on cnidarians, summarizing the molecular evidence for the conservation of a bilaterian-like circadian clock in anthozoan cnidarians, and presenting new empirical data supporting the presence of a conserved feed-forward loop in the starlet sea anemone, Nematostella vectensis. Furthermore, we discuss critical gaps in our current knowledge about the cnidarian clock, including the functions directly regulated by the clock and the precise molecular interactions that drive the oscillating gene-expression patterns. We conclude that the field of cnidarian circadian biology is moving rapidly toward linking molecular mechanisms with physiology and behavior. PMID:23620252

Water models based on a single potential energy surface and different molecular degrees of freedom

NASA Astrophysics Data System (ADS)

Saint-Martin, Humberto; Hernández-Cobos, Jorge; Ortega-Blake, Iván

2005-06-01

Up to now it has not been possible to neatly assess whether a deficient performance of a model is due to poor parametrization of the force field or the lack of inclusion of enough molecular properties. This work compares several molecular models in the framework of the same force field, which was designed to include many-body nonadditive effects: (a) a polarizable and flexible molecule with constraints that account for the quantal nature of the vibration [B. Hess, H. Saint-Martin, and H. J. C. Berendsen, J. Chem. Phys. 116, 9602 (2002), H. Saint-Martin, B. Hess, and H. J. C. Berendsen, J. Chem. Phys. 120, 11133 (2004)], (b) a polarizable and classically flexible molecule [H. Saint-Martin, J. Hernández-Cobos, M. I. Bernal-Uruchurtu, I. Ortega-Blake, and H. J. C. Berendsen, J. Chem. Phys. 113, 10899 (2000)], (c) a polarizable and rigid molecule, and finally (d) a nonpolarizable and rigid molecule. The goal is to determine how significant the different molecular properties are. The results indicate that all factors—nonadditivity, polarizability, and intramolecular flexibility—are important. Still, approximations can be made in order to diminish the computational cost of the simulations with a small decrease in the accuracy of the predictions, provided that those approximations are counterbalanced by the proper inclusion of an effective molecular property, that is, an average molecular geometry or an average dipole. Hence instead of building an effective force field by parametrizing it in order to reproduce the properties of a specific phase, a building approach is proposed that is based on adequately restricting the molecular flexibility and/or polarizability of a model potential fitted to unimolecular properties, pair interactions, and many-body nonadditive contributions. In this manner, the same parental model can be used to simulate the same substance under a wide range of thermodynamic conditions. An additional advantage of this approach is that, as the force field improves by the quality of the molecular calculations, all levels of modeling can be improved.

Molecular Dynamics of Hot Dense Plasmas: New Horizons

NASA Astrophysics Data System (ADS)

Graziani, Frank

2011-10-01

We describe the status of a new time-dependent simulation capability for hot dense plasmas. The backbone of this multi-institutional computational and experimental effort--the Cimarron Project--is the massively parallel molecular dynamics (MD) code ``ddcMD''. The project's focus is material conditions such as exist in inertial confinement fusion experiments, and in many stellar interiors: high temperatures, high densities, significant electromagnetic fields, mixtures of high- and low- Zelements, and non-Maxwellian particle distributions. Of particular importance is our ability to incorporate into this classical MD code key atomic, radiative, and nuclear processes, so that their interacting effects under non-ideal plasma conditions can be investigated. This talk summarizes progress in computational methodology, discusses strengths and weaknesses of quantum statistical potentials as effective interactions for MD, explains the model used for quantum events possibly occurring in a collision and highlights some significant results obtained to date. We describe the status of a new time-dependent simulation capability for hot dense plasmas. The backbone of this multi-institutional computational and experimental effort--the Cimarron Project--is the massively parallel molecular dynamics (MD) code ``ddcMD''. The project's focus is material conditions such as exist in inertial confinement fusion experiments, and in many stellar interiors: high temperatures, high densities, significant electromagnetic fields, mixtures of high- and low- Zelements, and non-Maxwellian particle distributions. Of particular importance is our ability to incorporate into this classical MD code key atomic, radiative, and nuclear processes, so that their interacting effects under non-ideal plasma conditions can be investigated. This talk summarizes progress in computational methodology, discusses strengths and weaknesses of quantum statistical potentials as effective interactions for MD, explains the model used for quantum events possibly occurring in a collision and highlights some significant results obtained to date. This work is performed under the auspices of the U. S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Molecular Environmental Science: An Assessment of Research Accomplishments, Available Synchrotron Radiation Facilities, and Needs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, G

2004-02-05

Synchrotron-based techniques are fundamental to research in ''Molecular Environmental Science'' (MES), an emerging field that involves molecular-level studies of chemical and biological processes affecting the speciation, properties, and behavior of contaminants, pollutants, and nutrients in the ecosphere. These techniques enable the study of aqueous solute complexes, poorly crystalline materials, solid-liquid interfaces, mineral-aqueous solution interactions, microbial biofilm-heavy metal interactions, heavy metal-plant interactions, complex material microstructures, and nanomaterials, all of which are important components or processes in the environment. Basic understanding of environmental materials and processes at the molecular scale is essential for risk assessment and management, and reduction of environmental pollutantsmore » at field, landscape, and global scales. One of the main purposes of this report is to illustrate the role of synchrotron radiation (SR)-based studies in environmental science and related fields and their impact on environmental problems of importance to society. A major driving force for MES research is the need to characterize, treat, and/or dispose of vast quantities of contaminated materials, including groundwater, sediments, and soils, and to process wastes, at an estimated cost exceeding 150 billion dollars through 2070. A major component of this problem derives from high-level nuclear waste. Other significant components come from mining and industrial wastes, atmospheric pollutants derived from fossil fuel consumption, agricultural pesticides and fertilizers, and the pollution problems associated with animal waste run-off, all of which have major impacts on human health and welfare. Addressing these problems requires the development of new characterization and processing technologies--efforts that require information on the chemical speciation of heavy metals, radionuclides, and xenobiotic organic compounds and their reactions with environmental materials. To achieve this goal, both fundamental and targeted studies of complex environmental systems at a molecular level are needed, and examples of both types of studies are presented herein. These examples illustrate the fact that MES SR studies have led to a revolution in our understanding of the fundamental physical and chemical aspects of natural systems. The MES SR user community has continued to experience strong growth at U.S. SR laboratories, with MES researchers comprising up to 15% of the total user base. Further growth and development of the MES community is being hindered by insufficient resources, including support personnel, materials preparation facilities, and available beam time at U.S. SR laboratories. ''EnviroSync'' recommends the following actions, in cooperation with U.S. SR laboratory directors, to meet the MES community's needs.« less

Molecular biomimetics: nanotechnology through biology.

PubMed

Sarikaya, Mehmet; Tamerler, Candan; Jen, Alex K-Y; Schulten, Klaus; Baneyx, François

2003-09-01

Proteins, through their unique and specific interactions with other macromolecules and inorganics, control structures and functions of all biological hard and soft tissues in organisms. Molecular biomimetics is an emerging field in which hybrid technologies are developed by using the tools of molecular biology and nanotechnology. Taking lessons from biology, polypeptides can now be genetically engineered to specifically bind to selected inorganic compounds for applications in nano- and biotechnology. This review discusses combinatorial biological protocols, that is, bacterial cell surface and phage-display technologies, in the selection of short sequences that have affinity to (noble) metals, semiconducting oxides and other technological compounds. These genetically engineered proteins for inorganics (GEPIs) can be used in the assembly of functional nanostructures. Based on the three fundamental principles of molecular recognition, self-assembly and DNA manipulation, we highlight successful uses of GEPI in nanotechnology.

2012 Gordon Research Conference on Cellular and Molecular Fungal Biology, Final Progress Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berman, Judith

The Gordon Research Conference on Cellular and Molecular Fungal Biology was held at Holderness School, Holderness New Hampshire, June 17 - 22, 2012. The 2012 Gordon Conference on Cellular and Molecular Fungal Biology (CMFB) will present the latest, cutting-edge research on the exciting and growing field of molecular and cellular aspects of fungal biology. Topics will range from yeast to filamentous fungi, from model systems to economically important organisms, and from saprophytes and commensals to pathogens of plants and animals. The CMFB conference will feature a wide range of topics including systems biology, cell biology and morphogenesis, organismal interactions, genomemore » organisation and regulation, pathogenesis, energy metabolism, biomass production and population genomics. The Conference was well-attended with 136 participants. Gordon Research Conferences does not permit publication of meeting proceedings.« less

Vibrational spectroscopic determination of local solvent electric field, solute-solvent electrostatic interaction energy, and their fluctuation amplitudes.

PubMed

Lee, Hochan; Lee, Gayeon; Jeon, Jonggu; Cho, Minhaeng

2012-01-12

IR probes have been extensively used to monitor local electrostatic and solvation dynamics. Particularly, their vibrational frequencies are highly sensitive to local solvent electric field around an IR probe. Here, we show that the experimentally measured vibrational frequency shifts can be inversely used to determine local electric potential distribution and solute-solvent electrostatic interaction energy. In addition, the upper limits of their fluctuation amplitudes are estimated by using the vibrational bandwidths. Applying this method to fully deuterated N-methylacetamide (NMA) in D(2)O and examining the solvatochromic effects on the amide I' and II' mode frequencies, we found that the solvent electric potential difference between O(═C) and D(-N) atoms of the peptide bond is about 5.4 V, and thus, the approximate solvent electric field produced by surrounding water molecules on the NMA is 172 MV/cm on average if the molecular geometry is taken into account. The solute-solvent electrostatic interaction energy is estimated to be -137 kJ/mol, by considering electric dipole-electric field interaction. Furthermore, their root-mean-square fluctuation amplitudes are as large as 1.6 V, 52 MV/cm, and 41 kJ/mol, respectively. We found that the water electric potential on a peptide bond is spatially nonhomogeneous and that the fluctuation in the electrostatic peptide-water interaction energy is about 10 times larger than the thermal energy at room temperature. This indicates that the peptide-solvent interactions are indeed important for the activation of chemical reactions in aqueous solution.

Electronic resonances in broadband stimulated Raman spectroscopy

NASA Astrophysics Data System (ADS)

Batignani, G.; Pontecorvo, E.; Giovannetti, G.; Ferrante, C.; Fumero, G.; Scopigno, T.

2016-01-01

Spontaneous Raman spectroscopy is a formidable tool to probe molecular vibrations. Under electronic resonance conditions, the cross section can be selectively enhanced enabling structural sensitivity to specific chromophores and reaction centers. The addition of an ultrashort, broadband femtosecond pulse to the excitation field allows for coherent stimulation of diverse molecular vibrations. Within such a scheme, vibrational spectra are engraved onto a highly directional field, and can be heterodyne detected overwhelming fluorescence and other incoherent signals. At variance with spontaneous resonance Raman, however, interpreting the spectral information is not straightforward, due to the manifold of field interactions concurring to the third order nonlinear response. Taking as an example vibrational spectra of heme proteins excited in the Soret band, we introduce a general approach to extract the stimulated Raman excitation profiles from complex spectral lineshapes. Specifically, by a quantum treatment of the matter through density matrix description of the third order nonlinear polarization, we identify the contributions which generate the Raman bands, by taking into account for the cross section of each process.

Biomolecular Force Field Parameterization via Atoms-in-Molecule Electron Density Partitioning.

PubMed

Cole, Daniel J; Vilseck, Jonah Z; Tirado-Rives, Julian; Payne, Mike C; Jorgensen, William L

2016-05-10

Molecular mechanics force fields, which are commonly used in biomolecular modeling and computer-aided drug design, typically treat nonbonded interactions using a limited library of empirical parameters that are developed for small molecules. This approach does not account for polarization in larger molecules or proteins, and the parametrization process is labor-intensive. Using linear-scaling density functional theory and atoms-in-molecule electron density partitioning, environment-specific charges and Lennard-Jones parameters are derived directly from quantum mechanical calculations for use in biomolecular modeling of organic and biomolecular systems. The proposed methods significantly reduce the number of empirical parameters needed to construct molecular mechanics force fields, naturally include polarization effects in charge and Lennard-Jones parameters, and scale well to systems comprised of thousands of atoms, including proteins. The feasibility and benefits of this approach are demonstrated by computing free energies of hydration, properties of pure liquids, and the relative binding free energies of indole and benzofuran to the L99A mutant of T4 lysozyme.

Recent Developments and Applications of the MMPBSA Method

PubMed Central

Wang, Changhao; Greene, D'Artagnan; Xiao, Li; Qi, Ruxi; Luo, Ray

2018-01-01

The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been widely applied as an efficient and reliable free energy simulation method to model molecular recognition, such as for protein-ligand binding interactions. In this review, we focus on recent developments and applications of the MMPBSA method. The methodology review covers solvation terms, the entropy term, extensions to membrane proteins and high-speed screening, and new automation toolkits. Recent applications in various important biomedical and chemical fields are also reviewed. We conclude with a few future directions aimed at making MMPBSA a more robust and efficient method. PMID:29367919

Optical signatures of coupled quantum dots.

PubMed

Stinaff, E A; Scheibner, M; Bracker, A S; Ponomarev, I V; Korenev, V L; Ware, M E; Doty, M F; Reinecke, T L; Gammon, D

2006-02-03

An asymmetric pair of coupled InAs quantum dots is tuned into resonance by applying an electric field so that a single hole forms a coherent molecular wave function. The optical spectrum shows a rich pattern of level anticrossings and crossings that can be understood as a superposition of charge and spin configurations of the two dots. Coulomb interactions shift the molecular resonance of the optically excited state (charged exciton) with respect to the ground state (single charge), enabling light-induced coupling of the quantum dots. This result demonstrates the possibility of optically coupling quantum dots for application in quantum information processing.

Optical Signatures of Coupled Quantum Dots

NASA Astrophysics Data System (ADS)

Stinaff, E. A.; Scheibner, M.; Bracker, A. S.; Ponomarev, I. V.; Korenev, V. L.; Ware, M. E.; Doty, M. F.; Reinecke, T. L.; Gammon, D.

2006-02-01

An asymmetric pair of coupled InAs quantum dots is tuned into resonance by applying an electric field so that a single hole forms a coherent molecular wave function. The optical spectrum shows a rich pattern of level anticrossings and crossings that can be understood as a superposition of charge and spin configurations of the two dots. Coulomb interactions shift the molecular resonance of the optically excited state (charged exciton) with respect to the ground state (single charge), enabling light-induced coupling of the quantum dots. This result demonstrates the possibility of optically coupling quantum dots for application in quantum information processing.

Regulation of bone by the adaptive immune system in arthritis

PubMed Central

2011-01-01

Studies on the immune regulation of osteoclasts in rheumatoid arthritis have promoted the new research field of 'osteoimmunology', which investigates the interplay between the skeletal and immune systems at the molecular level. Accumulating evidence lends support to the theory that bone destruction associated with rheumatoid arthritis is caused by the enhanced activity of osteoclasts, resulting from the activation of a unique helper T cell subset, 'Th17 cells'. Understanding the interaction between osteoclasts and the adaptive immune system in rheumatoid arthritis and the molecular mechanisms of Th17 development will lead to the development of potentially effective therapeutic strategies. PMID:21635718

Molecular simulations of carbohydrates and protein-carbohydrate interactions: motivation, issues and prospects.

PubMed

Fadda, Elisa; Woods, Robert J

2010-08-01

The characterization of the 3D structure of oligosaccharides, their conjugates and analogs is particularly challenging for traditional experimental methods. Molecular simulation methods provide a basis for interpreting sparse experimental data and for independently predicting conformational and dynamic properties of glycans. Here, we summarize and analyze the issues associated with modeling carbohydrates, with a detailed discussion of four of the most recently developed carbohydrate force fields, reviewed in terms of applicability to natural glycans, carbohydrate-protein complexes and the emerging area of glycomimetic drugs. In addition, we discuss prospectives and new applications of carbohydrate modeling in drug discovery.

Tetrazine ligation for chemical proteomics.

PubMed

Kang, Kyungtae; Park, Jongmin; Kim, Eunha

2016-01-01

Determining small molecule-target protein interaction is essential for the chemical proteomics. One of the most important keys to explore biological system in chemical proteomics field is finding first-class molecular tools. Chemical probes can provide great spatiotemporal control to elucidate biological functions of proteins as well as for interrogating biological pathways. The invention of bioorthogonal chemistry has revolutionized the field of chemical biology by providing superior chemical tools and has been widely used for investigating the dynamics and function of biomolecules in live condition. Among 20 different bioorthogonal reactions, tetrazine ligation has been spotlighted as the most advanced bioorthogonal chemistry because of their extremely faster kinetics and higher specificity than others. Therefore, tetrazine ligation has a tremendous potential to enhance the proteomic research. This review highlights the current status of tetrazine ligation reaction as a molecular tool for the chemical proteomics.

The Nature of the Dielectric Response of Methanol Revealed by the Terahertz Kerr Effect.

PubMed

Kampfrath, Tobias; Campen, R Kramer; Wolf, Martin; Sajadi, Mohsen

2018-03-15

The dielectric response of liquids in the terahertz (THz) and sub-THz frequency range arises from low-energy collective molecular motions, which are often strongly influenced by intermolecular interactions. To shed light on the microscopic origin of the THz dielectric response of the simplest alcohol, methanol, we resonantly excite this liquid with an intense THz electric-field pulse and monitor the relaxation of the induced optical birefringence. We find a unipolar THz-Kerr-effect signal which, in contrast to aprotic polar liquids, shows a weak coupling between the THz electric field and the permanent molecular dipole moment of the liquid. We assign this weak coupling to the restricted translational rather than rotational nature of the excited mode. Our approach opens a new avenue to the assignment of the dielectric spectrum of liquids to a microscopic origin.

A structural mechanics approach for the phonon dispersion analysis of graphene

NASA Astrophysics Data System (ADS)

Hou, X. H.; Deng, Z. C.; Zhang, K.

2017-04-01

A molecular structural mechanics model for the numerical simulation of phonon dispersion relations of graphene is developed by relating the C-C bond molecular potential energy to the strain energy of the equivalent beam-truss space frame. With the stiffness matrix known and further based on the periodic structure characteristics, the Bloch theorem is introduced to develop the dispersion relation of graphene sheet. Being different from the existing structural mechanics model, interactions between the fourth-nearest neighbor atoms are further simulated with beam elements to compensate the reduced stretching stiffness, where as a result not only the dispersion relations in the low frequency field are accurately achieved, but results in the high frequency field are also reasonably obtained. This work is expected to provide new opportunities for the dynamic properties analysis of graphene and future application in the engineering sector.

On the sufficiency of pairwise interactions in maximum entropy models of networks

NASA Astrophysics Data System (ADS)

Nemenman, Ilya; Merchan, Lina

Biological information processing networks consist of many components, which are coupled by an even larger number of complex multivariate interactions. However, analyses of data sets from fields as diverse as neuroscience, molecular biology, and behavior have reported that observed statistics of states of some biological networks can be approximated well by maximum entropy models with only pairwise interactions among the components. Based on simulations of random Ising spin networks with p-spin (p > 2) interactions, here we argue that this reduction in complexity can be thought of as a natural property of some densely interacting networks in certain regimes, and not necessarily as a special property of living systems. This work was supported in part by James S. McDonnell Foundation Grant No. 220020321.

A Force Balanced Fragmentation Method for ab Initio Molecular Dynamic Simulation of Protein.

PubMed

Xu, Mingyuan; Zhu, Tong; Zhang, John Z H

2018-01-01

A force balanced generalized molecular fractionation with conjugate caps (FB-GMFCC) method is proposed for ab initio molecular dynamic simulation of proteins. In this approach, the energy of the protein is computed by a linear combination of the QM energies of individual residues and molecular fragments that account for the two-body interaction of hydrogen bond between backbone peptides. The atomic forces on the caped H atoms were corrected to conserve the total force of the protein. Using this approach, ab initio molecular dynamic simulation of an Ace-(ALA) 9 -NME linear peptide showed the conservation of the total energy of the system throughout the simulation. Further a more robust 110 ps ab initio molecular dynamic simulation was performed for a protein with 56 residues and 862 atoms in explicit water. Compared with the classical force field, the ab initio molecular dynamic simulations gave better description of the geometry of peptide bonds. Although further development is still needed, the current approach is highly efficient, trivially parallel, and can be applied to ab initio molecular dynamic simulation study of large proteins.

AMOEBA 2.0: A physics-first approach to biomolecular simulations

NASA Astrophysics Data System (ADS)

Rackers, Joshua; Ponder, Jay

The goal of the AMOEBA force field project is to use classical physics to understand and predict the nature of interactions between biological molecules. While making significant advances over the past decade, the ultimate goal of predicting binding energies with ``chemical accuracy'' remains elusive. The primary source of this inaccuracy comes from the physics of how molecules interact at short range. For example, despite AMOEBA's advanced treatment of electrostatics, the force field dramatically overpredicts the electrostatic energy of DNA stacking interactions. AMOEBA 2.0 works to correct these errors by including simple, first principles physics-based terms to account for the quantum mechanical nature of these short-range molecular interactions. We have added a charge penetration term that considerably improves the description of electrostatic interactions at short range. We are reformulating the polarization term of AMOEBA in terms of basic physics assertions. And we are reevaluating the van der Waals term to match ab initio energy decompositions. These additions and changes promise to make AMOEBA more predictive. By including more physical detail of the important short-range interactions of biological molecules, we hope to move closer to the ultimate goal of true predictive power.

Coherent control of molecular alignment of homonuclear diatomic molecules by analytically designed laser pulses.

PubMed

Zou, Shiyang; Sanz, Cristina; Balint-Kurti, Gabriel G

2008-09-28

We present an analytic scheme for designing laser pulses to manipulate the field-free molecular alignment of a homonuclear diatomic molecule. The scheme is based on the use of a generalized pulse-area theorem and makes use of pulses constructed around two-photon resonant frequencies. In the proposed scheme, the populations and relative phases of the rovibrational states of the molecule are independently controlled utilizing changes in the laser intensity and in the carrier-envelope phase difference, respectively. This allows us to create the correct coherent superposition of rovibrational states needed to achieve optimal molecular alignment. The validity and efficiency of the scheme are demonstrated by explicit application to the H(2) molecule. The analytically designed laser pulses are tested by exact numerical solutions of the time-dependent Schrodinger equation including laser-molecule interactions to all orders of the field strength. The design of a sequence of pulses to further enhance molecular alignment is also discussed and tested. It is found that the rotating wave approximation used in the analytic design of the laser pulses leads to small errors in the prediction of the relative phase of the rotational states. It is further shown how these errors may be easily corrected.

Laser manipulation of atomic and molecular flows

NASA Astrophysics Data System (ADS)

Lilly, Taylor C.

The continuing advance of laser technology enables a range of broadly applicable, laser-based flow manipulation techniques. The characteristics of these laser-based flow manipulations suggest that they may augment, or be superior to, such traditional electro-mechanical methods as ionic flow control, shock tubes, and small scale wind tunnels. In this study, methodology was developed for investigating laser flow manipulation techniques, and testing their feasibility for a number of aerospace, basic physics, and micro technology applications. Theories for laser-atom and laser-molecule interactions have been under development since the advent of laser technology. The theories have yet to be adequately integrated into kinetic flow solvers. Realizing this integration would greatly enhance the scaling of laser-species interactions beyond the realm of ultra-cold atomic physics. This goal was realized in the present study. A representative numerical investigation, of laser-based neutral atomic and molecular flow manipulations, was conducted using near-resonant and non-resonant laser fields. To simulate the laser interactions over a range of laser and flow conditions, the following tools were employed: a custom collisionless gas particle trajectory code and a specifically modified version of the Direct Simulation Monte Carlo statistical kinetic solver known as SMILE. In addition to the numerical investigations, a validating experiment was conducted. The experimental results showed good agreement with the numerical simulations when experimental parameters, such as finite laser line width, were taken into account. Several areas of interest were addressed: laser induced neutral flow steering, collimation, direct flow acceleration, and neutral gas heating. Near-resonant continuous wave laser, and non-resonant pulsed laser, interactions with cesium and nitrogen were simulated. These simulations showed trends and some limitations associated with these interactions, used for flow steering and collimation. The use of one of these interactions, the induced dipole force, was extended beyond a single Gaussian laser field. The interference patterns associated with counter-propagating laser fields, or "optical lattices," were shown to be capable of both direct species acceleration and gas heating. This study resulted in predictions for a continuous, resonant laser-cesium flow with accelerations of 106 m/s2. For this circumstance, a future straightforward proof of principle experiment has been identified. To demonstrate non-resonant gas heating, a series of pulsed optical lattices were simulated interacting with neutral non-polar species. An optimum time between pulses was identified as a function of the collisional relaxation time. Using the optimum time between pulses, molecular nitrogen simulations showed an increase in gas temperature from 300 K to 2470 K at 1 atm, for 50 successive optical lattice pulses. A second proof of principle experiment was identified for future investigation.

Force Field for Water Based on Neural Network.

PubMed

Wang, Hao; Yang, Weitao

2018-05-18

We developed a novel neural network based force field for water based on training with high level ab initio theory. The force field was built based on electrostatically embedded many-body expansion method truncated at binary interactions. Many-body expansion method is a common strategy to partition the total Hamiltonian of large systems into a hierarchy of few-body terms. Neural networks were trained to represent electrostatically embedded one-body and two-body interactions, which require as input only one and two water molecule calculations at the level of ab initio electronic structure method CCSD/aug-cc-pVDZ embedded in the molecular mechanics water environment, making it efficient as a general force field construction approach. Structural and dynamic properties of liquid water calculated with our force field show good agreement with experimental results. We constructed two sets of neural network based force fields: non-polarizable and polarizable force fields. Simulation results show that the non-polarizable force field using fixed TIP3P charges has already behaved well, since polarization effects and many-body effects are implicitly included due to the electrostatic embedding scheme. Our results demonstrate that the electrostatically embedded many-body expansion combined with neural network provides a promising and systematic way to build the next generation force fields at high accuracy and low computational costs, especially for large systems.

Strong Local-Field Enhancement of the Nonlinear Soft-Mode Response in a Molecular Crystal

NASA Astrophysics Data System (ADS)

Folpini, Giulia; Reimann, Klaus; Woerner, Michael; Elsaesser, Thomas; Hoja, Johannes; Tkatchenko, Alexandre

2017-09-01

The nonlinear response of soft-mode excitations in polycrystalline acetylsalicylic acid (aspirin) is studied with two-dimensional terahertz spectroscopy. We demonstrate that the correlation of CH3 rotational modes with collective oscillations of π electrons drives the system into the nonperturbative regime of light-matter interaction, even for a moderate strength of the THz driving field on the order of 50 kV /cm . Nonlinear absorption around 1.1 THz leads to a blueshifted coherent emission at 1.7 THz, revealing the dynamic breakup of the strong electron-phonon correlations. The observed behavior is reproduced by theoretical calculations including dynamic local-field correlations.

Binding preference of carbon nanotube over proline-rich motif ligand on SH3-domain: a comparison with different force fields.

PubMed

Shi, Biyun; Zuo, Guanghong; Xiu, Peng; Zhou, Ruhong

2013-04-04

With the widespread applications of nanomaterials such as carbon nanotubes, there is a growing concern on the biosafety of these engineered nanoparticles, in particular their interactions with proteins. In molecular simulations of nanoparticle-protein interactions, the choice of empirical parameters (force fields) plays a decisive role, and thus is of great importance and should be examined carefully before wider applications. Here we compare three commonly used force fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding of a single wall carbon nanotube (SWCNT) with a native proline-rich motif (PRM) ligand on its target protein SH3 domain, a ubiquitous protein-protein interaction mediator involved in signaling and regulatory pathways. We find that the SWCNT displays a general preference over the PRM in binding with SH3 domain in all the three force fields examined, although the degree of preference can be somewhat different, with the AMBER force field showing the highest preference. The SWCNT prevents the ligand from reaching its native binding pocket by (i) occupying the binding pocket directly, and (ii) binding with the ligand itself and then being trapped together onto some off-sites. The π-π stacking interactions between the SWCNT and aromatic residues are found to play a significant role in its binding to the SH3 domain in all the three force fields. Further analyses show that even the SWCNT-ligand binding can also be relatively more stable than the native ligand-protein binding, indicating a serious potential disruption to the protein SH3 function.

TMFF-A Two-Bead Multipole Force Field for Coarse-Grained Molecular Dynamics Simulation of Protein.

PubMed

Li, Min; Liu, Fengjiao; Zhang, John Z H

2016-12-13

Coarse-grained (CG) models are desirable for studying large and complex biological systems. In this paper, we propose a new two-bead multipole force field (TMFF) in which electric multipoles up to the quadrupole are included in the CG force field. The inclusion of electric multipoles in the proposed CG force field enables a more realistic description of the anisotropic electrostatic interactions in the protein system and, thus, provides an improvement over the standard isotropic two-bead CG models. In order to test the accuracy of the new CG force field model, extensive molecular dynamics simulations were carried out for a series of benchmark protein systems. These simulation studies showed that the TMFF model can realistically reproduce the structural and dynamical properties of proteins, as demonstrated by the close agreement of the CG results with those from the corresponding all-atom simulations in terms of root-mean-square deviations (RMSDs) and root-mean-square fluctuations (RMSFs) of the protein backbones. The current two-bead model is highly coarse-grained and is 50-fold more efficient than all-atom method in MD simulation of proteins in explicit water.

Parameterization of an interfacial force field for accurate representation of peptide adsorption free energy on high-density polyethylene

PubMed Central

Abramyan, Tigran M.; Snyder, James A.; Yancey, Jeremy A.; Thyparambil, Aby A.; Wei, Yang; Stuart, Steven J.; Latour, Robert A.

2015-01-01

Interfacial force field (IFF) parameters for use with the CHARMM force field have been developed for interactions between peptides and high-density polyethylene (HDPE). Parameterization of the IFF was performed to achieve agreement between experimental and calculated adsorption free energies of small TGTG–X–GTGT host–guest peptides (T = threonine, G = glycine, and X = variable amino-acid residue) on HDPE, with ±0.5 kcal/mol agreement. This IFF parameter set consists of tuned nonbonded parameters (i.e., partial charges and Lennard–Jones parameters) for use with an in-house-modified CHARMM molecular dynamic program that enables the use of an independent set of force field parameters to control molecular behavior at a solid–liquid interface. The R correlation coefficient between the simulated and experimental peptide adsorption free energies increased from 0.00 for the standard CHARMM force field parameters to 0.88 for the tuned IFF parameters. Subsequent studies are planned to apply the tuned IFF parameter set for the simulation of protein adsorption behavior on an HDPE surface for comparison with experimental values of adsorbed protein orientation and conformation. PMID:25818122

Molecular simulation of gas adsorption and diffusion in a breathing MOF using a rigid force field.

PubMed

García-Pérez, E; Serra-Crespo, P; Hamad, S; Kapteijn, F; Gascon, J

2014-08-14

Simulation of gas adsorption in flexible porous materials is still limited by the slow progress in the development of flexible force fields. Moreover, the high computational cost of such flexible force fields may be a drawback even when they are fully developed. In this work, molecular simulations of gas adsorption and diffusion of carbon dioxide and methane in NH2-MIL-53(Al) are carried out using a linear combination of two crystallographic structures with rigid force fields. Once the interactions of carbon dioxide molecules and the bridging hydroxyls groups of the framework are optimized, an excellent match is found for simulations and experimental data for the adsorption of methane and carbon dioxide, including the stepwise uptake due to the breathing effect. In addition, diffusivities of pure components are calculated. The pore expansion by the breathing effect influences the self-diffusion mechanism and much higher diffusivities are observed at relatively high adsorbate loadings. This work demonstrates that using a rigid force field combined with a minimum number of experiments, reproduces adsorption and simulates diffusion of carbon dioxide and methane in the flexible metal-organic framework NH2-MIL-53(Al).

Osmotic Pressure Simulations of Amino Acids and Peptides Highlight Potential Routes to Protein Force Field Parameterization

PubMed Central

Miller, Mark S.; Lay, Wesley K.

2016-01-01

Recent molecular dynamics (MD) simulations of proteins have suggested that common force fields overestimate the strength of amino acid interactions in aqueous solution. In an attempt to determine the causes of these effects, we have measured the osmotic coefficients of a number of amino acids using the AMBER ff99SB-ILDN force field with two popular water models, and compared the results with available experimental data. With TIP4P-Ew water, interactions between aliphatic residues agree well with experiment, but interactions of the polar residues serine and threonine are found to be excessively attractive. For all tested amino acids, the osmotic coefficients are lower when the TIP3P water model is used. Additional simulations performed on charged amino acids indicate that the osmotic coefficients are strongly dependent on the parameters assigned to the salt ions, with a reparameterization of the sodium:carboxylate interaction reported by the Aksimentiev group significantly improving description of the osmotic coefficient for glutamate. For five neutral amino acids, we also demonstrate a decrease in solute-solute attractions using the recently reported TIP4P-D water model and using the KBFF force field. Finally, we show that for four two-residue peptides improved agreement with experiment can be achieved by re-deriving the partial charges for each peptide. PMID:27052117

Essential amino acids interacting with flavonoids: A theoretical approach

NASA Astrophysics Data System (ADS)

Codorniu-Hernández, Edelsys; Mesa-Ibirico, Ariel; Hernández-Santiesteban, Richel; Montero-Cabrera, Luis A.; Martínez-Luzardo, Francisco; Santana-Romero, Jorge L.; Borrmann, Tobias; Stohrer, Wolf-D.

The interaction of two flavonoid species (resorcinolic and fluoroglucinolic) with the 20 essential amino acids was studied by the multiple minima hypersurface (MMH) procedures, through the AM1 and PM3 semiempirical methods. Remarkable thermodynamic data related to the properties of the molecular association of these compounds were obtained, which will be of great utility for future investigations concerning the interaction of flavonoids with proteins. These results are compared with experimental and classical force field results reported in the available literature, and new evidences and criteria are shown. The hydrophilic amino acids demonstrated high affinity in the interaction with flavonoid molecules; the complexes with lysine are especially extremely stable. An affinity order for the interaction of both flavonoid species with the essential amino acids is suggested. Our theoretical results are compared with experimental evidence on flavonoid interactions with proteins of biomedical interest.

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.

PubMed

Šponer, Jiří; Bussi, Giovanni; Krepl, Miroslav; Banáš, Pavel; Bottaro, Sandro; Cunha, Richard A; Gil-Ley, Alejandro; Pinamonti, Giovanni; Poblete, Simón; Jurečka, Petr; Walter, Nils G; Otyepka, Michal

2018-04-25

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA-ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field.

Characterization and kinetics of surface functionalization and binding of biologically and chemically significant molecules

NASA Astrophysics Data System (ADS)

Steiner, Rachel

The purpose of this project is to investigate intermolecular interactions of organic molecular assemblies. By understanding the structure and physical interactions in these assemblies, we gain insights into practical applications for nanoscale systems built upon these surface structures. It is possible for organic chemists to create many forms of modified organic molecules, functionalizing them with specific reactive end groups. Through surface functionalization, enabling covalent or highly associative binding, it is possible to create ordered molecular assemblies of these molecules. Scientists can study the nature of this structure and the intermolecular interactions through spectroscopic, optical, and scattering experiments. To understand the self-assembly process in molecular systems, we preliminarily created monolayer films on silica substrates with a variety of organic molecules. In particular, we functionalized silica substrates with hydroxyl groups and covalently bound acid chloride functionalized aromatic compounds, with and without an underlying adhesion layer of 3-aminopropyltriethoxysilane. We characterized the monolayer assemblies with ellipsometry, UV-vis absorption spectroscopy, FTIR spectroscopy, and fluorescence/photoemission spectroscopy, obtaining a quantitative measure of the molecular surface coverage. In order to understand the nature of these molecular assemblies, we also pursued an in-depth kinetic study to control and optimize the monolayer formation process. Through use of UV-vis spectroscopy, we determined that the monolayer formation can best be modeled with diffusion-limited Langmuir kinetics. Specifically, we concluded that for anthracene acid chloride in dichloromethane the average diffusion coefficient was 1.6x10-7 cm2/sec. Additionally, we find we are able to achieve surface coverages of approximately 2x1014 molecules/cm2. Having established the ability to create ordered molecular assemblies, through surface functionalization, enabling covalent or highly associative binding, we continued to explore the field of molecular assemblies by studying the binding and structure of molecules to carbon nanostructures. Previous studies have shown that alkyl side chains and aromatic compounds, such as pyrene, will bind non-covalently to the sidewalls of carbon nanotubes through pi-pi interactions. We explored functionalization of carbon nanotubes and graphene by using microscopy to examine the adsorption of biomolecules onto nanotube sidewalls and graphene.

A Massively Parallel Particle Code for Rarefied Ionized and Neutral Gas Flows in Earth and Planetary Atmospheres, Ionospheres and Magnetospheres

NASA Technical Reports Server (NTRS)

Combi, Michael R.

2004-01-01

In order to understand the global structure, dynamics, and physical and chemical processes occurring in the upper atmospheres, exospheres, and ionospheres of the Earth, the other planets, comets and planetary satellites and their interactions with their outer particles and fields environs, it is often necessary to address the fundamentally non-equilibrium aspects of the physical environment. These are regions where complex chemistry, energetics, and electromagnetic field influences are important. Traditional approaches are based largely on hydrodynamic or magnetohydrodynamic MHD) formulations and are very important and highly useful. However, these methods often have limitations in rarefied physical regimes where the molecular collision rates and ion gyrofrequencies are small and where interactions with ionospheres and upper neutral atmospheres are important.

Thermodynamics of Small Alkali Metal Halide Cluster Ions: Comparison of Classical Molecular Simulations with Experiment and Quantum Chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vlcek, Lukas; Uhlik, Filip; Moucka, Filip

We evaluate the ability of selected classical molecular models to describe the thermodynamic and structural aspects of gas-phase hydration of alkali halide ions and the formation of small water clusters. To understand the effect of many-body interactions (polarization) and charge penetration effects on the accuracy of a force field, we perform Monte Carlo simulations with three rigid water models using different functional forms to account for these effects: (i) point charge non-polarizable SPC/E, (ii) Drude point charge polarizable SWM4- DP, and (iii) Drude Gaussian charge polarizable BK3. Model predictions are compared with experimental Gibbs free energies and enthalpies of ionmore » hydration, and with microscopic structural properties obtained from quantum DFT calculations. We find that all three models provide comparable predictions for pure water clusters and cation hydration, but differ significantly in their description of anion hydration. None of the investigated classical force fields can consistently and quantitatively reproduce the experimental gas phase hydration thermodynamics. The outcome of this study highlights the relation between the functional form that describes the effective intermolecular interactions and the accuracy of the resulting ion hydration properties.« less

Deconstructing Free Energies in the Law of Matching Water Affinities.

PubMed

Shi, Yu; Beck, Thomas

2017-03-09

The law of matching water affinities (LMWA) is explored in classical molecular dynamics simulations of several alkali halide ion pairs, spanning the size range from small kosmotropes to large chaotropes. The ion-ion potentials of mean force (PMFs) are computed using three methods: the local molecular field theory (LMFT), the weighted histogram analysis method (WHAM), and integration of the average force. All three methods produce the same total PMF for a given ion pair. In addition, LMFT-based partitioning into van der Waals and local and far-field electrostatic free energies and assessment of the enthalpic, entropic, and ion-water components yield insights into the origins of the observed free energy profiles in water. The results highlight the importance of local electrostatic interactions in determining the shape of the PMFs, while longer-ranged interactions enhance the overall ion-ion attraction, as expected in a dielectric continuum model. The association equilibrium constants are estimated from the smooth WHAM curves and compared to available experimental conductance data. By examining the variations in the average hydration numbers of ions with ion-ion distance, a correlation of the water structure in the hydration shells with the free energy features is found.

First report on 3D-QSAR and molecular dynamics based docking studies of GCPII inhibitors for targeted drug delivery applications

NASA Astrophysics Data System (ADS)

Pandit, Amit; Sengupta, Sagnik; Krishnan, Mena Asha; Reddy, Ramesh B.; Sharma, Rajesh; Venkatesh, Chelvam

2018-05-01

Prostate Specific Membrane Antigen (PSMA) or Glutamate carboxypeptidase II (GCPII) has been identified as an important target in diagnosis and therapy of prostate cancer. Among several types of inhibitors, urea based inhibitors are the most common and widely employed in preclinical and clinical studies. Computational studies have been carried out to uncover active sites and interaction of PSMA inhibitors with the protein by modifying the core structure of the ligand. Analysis of the literature, however, show lack of 3-D quantitative structure activity relationship (QSAR) and molecular dynamics based molecular docking study to identify structural modifications responsible for better GCPII inhibitory activity. The present study aims to fulfil this gap by analysing well known PSMA inhibitors reported in the literature with known experimental PSMA inhibition constants. Also in order to validate the in silico study, a new GCPII inhibitor 7 was designed, synthesized and experimental PSMA enzyme inhibition was evaluated by using freshly isolated PSMA protein from human cancer cell line derived from lymph node, LNCaP. 3D-QSAR CoMFA models on 58 urea based GCPII inhibitors were generated, and the best correlation was obtained in Gast-Huck charge assigning method with q2, r2 and predictive r2 values as 0.592, 0.995 and 0.842 respectively. Moreover, steric, electrostatic, and hydrogen bond donor field contribution analysis provided best statistical values from CoMSIA model (q2, r2 and predictive r2 as 0.527, 0.981 and 0.713 respectively). Contour maps study revealed that electrostatic field contribution is the major factor for discovering better binding affinity ligands. Further molecular dynamic assisted molecular docking was also performed on GCPII receptor (PDB ID 4NGM) and most active GCPII inhibitor, DCIBzL. 4NGM co-crystallised ligand, JB7 was used to validate the docking procedure and the amino acid interactions present in JB7 are compared with DCIBzL. The results suggest that Arg210, Asn257, Gly518, Tyr552, Lys699, and Tyr700 amino acid residues may play a crucial role in GCPII inhibition. Molecular Dynamics Simulation provides information about docked pose stability of DCIBzL. By combination of CoMFA-CoMSIA field analysis and docking interaction analysis studies, conclusive SAR was generated for urea based derivatives based on which GCPII inhibitor 7 was designed and chemically synthesized in our laboratory. Evaluation of GCPII inhibitory activity of 7 by performing NAALADase assay provided IC50 value of 113 nM which is in close agreement with in silico predicted value (119 nM). Thus we have successfully validated our 3D-QSAR and molecular docking based designing of GCPII inhibitors methodology through biological experiments. This conclusive SAR would be helpful to generate novel and more potent GCPII inhibitors for drug delivery applications.

Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation

PubMed Central

Wang, Wenchao; Li, Zhiyuan; Liu, Juanjuan; Yang, Xingxing; Ji, Xinmiao; Luo, Yan; Hu, Chen; Hou, Yubin; He, Qianqian; Fang, Jun; Wang, Junfeng; Liu, Qingsong; Li, Guohui; Lu, Qingyou; Zhang, Xin

2016-01-01

Static magnetic fields (SMFs) can affect cell proliferation in a cell-type and intensity-dependent way but the mechanism remains unclear. At the same time, although the diamagnetic anisotropy of proteins has been proposed decades ago, the behavior of isolated proteins in magnetic fields has not been directly observed. Here we show that SMFs can affect isolated proteins at the single molecular level in an intensity-dependent manner. We found that Epidermal Growth Factor Receptor (EGFR), a protein that is overexpressed and highly activated in multiple cancers, can be directly inhibited by SMFs. Using Liquid-phase Scanning Tunneling Microscopy (STM) to examine pure EGFR kinase domain proteins at the single molecule level in solution, we observed orientation changes of these proteins in response to SMFs. This may interrupt inter-molecular interactions between EGFR monomers, which are critical for their activation. In molecular dynamics (MD) simulations, 1-9T SMFs caused increased probability of EGFR in parallel with the magnetic field direction in an intensity-dependent manner. A superconducting ultrastrong 9T magnet reduced proliferation of CHO-EGFR cells (Chinese Hamster Ovary cells with EGFR overexpression) and EGFR-expressing cancer cell lines by ~35%, but minimally affected CHO cells. We predict that similar effects of magnetic fields can also be applied to some other proteins such as ion channels. Our paper will help clarify some dilemmas in this field and encourage further investigations in order to achieve a better understanding of the biological effects of SMFs. PMID:27223425

Targeting the cell wall of Mycobacterium tuberculosis: a molecular modeling investigation of the interaction of imipenem and meropenem with L,D-transpeptidase 2.

PubMed

Silva, José Rogério A; Bishai, William R; Govender, Thavendran; Lamichhane, Gyanu; Maguire, Glenn E M; Kruger, Hendrik G; Lameira, Jeronimo; Alves, Cláudio N

2016-01-01

The single crystal X-ray structure of the extracellular portion of the L,D-transpeptidase (ex-LdtMt2 - residues 120-408) enzyme was recently reported. It was observed that imipenem and meropenem inhibit activity of this enzyme, responsible for generating L,D-transpeptide linkages in the peptidoglycan layer of Mycobacterium tuberculosis. Imipenem is more active and isothermal titration calorimetry experiments revealed that meropenem is subjected to an entropy penalty upon binding to the enzyme. Herein, we report a molecular modeling approach to obtain a molecular view of the inhibitor/enzyme interactions. The average binding free energies for nine commercially available inhibitors were calculated using MM/GBSA and Solvation Interaction Energy (SIE) approaches and the calculated energies corresponded well with the available experimentally observed results. The method reproduces the same order of binding energies as experimentally observed for imipenem and meropenem. We have also demonstrated that SIE is a reasonably accurate and cost-effective free energy method, which can be used to predict carbapenem affinities for this enzyme. A theoretical explanation was offered for the experimental entropy penalty observed for meropenem, creating optimism that this computational model can serve as a potential computational model for other researchers in the field.

Computer Folding of RNA Tetraloops: Identification of Key Force Field Deficiencies.

PubMed

Kührová, Petra; Best, Robert B; Bottaro, Sandro; Bussi, Giovanni; Šponer, Jiří; Otyepka, Michal; Banáš, Pavel

2016-09-13

The computer-aided folding of biomolecules, particularly RNAs, is one of the most difficult challenges in computational structural biology. RNA tetraloops are fundamental RNA motifs playing key roles in RNA folding and RNA-RNA and RNA-protein interactions. Although state-of-the-art Molecular Dynamics (MD) force fields correctly describe the native state of these tetraloops as a stable free-energy basin on the microsecond time scale, enhanced sampling techniques reveal that the native state is not the global free energy minimum, suggesting yet unidentified significant imbalances in the force fields. Here, we tested our ability to fold the RNA tetraloops in various force fields and simulation settings. We employed three different enhanced sampling techniques, namely, temperature replica exchange MD (T-REMD), replica exchange with solute tempering (REST2), and well-tempered metadynamics (WT-MetaD). We aimed to separate problems caused by limited sampling from those due to force-field inaccuracies. We found that none of the contemporary force fields is able to correctly describe folding of the 5'-GAGA-3' tetraloop over a range of simulation conditions. We thus aimed to identify which terms of the force field are responsible for this poor description of TL folding. We showed that at least two different imbalances contribute to this behavior, namely, overstabilization of base-phosphate and/or sugar-phosphate interactions and underestimated stability of the hydrogen bonding interaction in base pairing. The first artifact stabilizes the unfolded ensemble, while the second one destabilizes the folded state. The former problem might be partially alleviated by reparametrization of the van der Waals parameters of the phosphate oxygens suggested by Case et al., while in order to overcome the latter effect we suggest local potentials to better capture hydrogen bonding interactions.

MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

PubMed

Caetano, Fabiana A; Dirk, Brennan S; Tam, Joshua H K; Cavanagh, P Craig; Goiko, Maria; Ferguson, Stephen S G; Pasternak, Stephen H; Dikeakos, Jimmy D; de Bruyn, John R; Heit, Bryan

2015-12-01

Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR) software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell.

A loop-gap resonator for chirality-sensitive nuclear magneto-electric resonance (NMER)

NASA Astrophysics Data System (ADS)

Garbacz, Piotr; Fischer, Peer; Krämer, Steffen

2016-09-01

Direct detection of molecular chirality is practically impossible by methods of standard nuclear magnetic resonance (NMR) that is based on interactions involving magnetic-dipole and magnetic-field operators. However, theoretical studies provide a possible direct probe of chirality by exploiting an enantiomer selective additional coupling involving magnetic-dipole, magnetic-field, and electric field operators. This offers a way for direct experimental detection of chirality by nuclear magneto-electric resonance (NMER). This method uses both resonant magnetic and electric radiofrequency (RF) fields. The weakness of the chiral interaction though requires a large electric RF field and a small transverse RF magnetic field over the sample volume, which is a non-trivial constraint. In this study, we present a detailed study of the NMER concept and a possible experimental realization based on a loop-gap resonator. For this original device, the basic principle and numerical studies as well as fabrication and measurements of the frequency dependence of the scattering parameter are reported. By simulating the NMER spin dynamics for our device and taking the 19F NMER signal of enantiomer-pure 1,1,1-trifluoropropan-2-ol, we predict a chirality induced NMER signal that accounts for 1%-5% of the standard achiral NMR signal.

Cross-talk between topological defects in different fields revealed by nematic microfluidics

PubMed Central

Giomi, Luca; Kos, Žiga; Ravnik, Miha

2017-01-01

Topological defects are singularities in material fields that play a vital role across a range of systems: from cosmic microwave background polarization to superconductors and biological materials. Although topological defects and their mutual interactions have been extensively studied, little is known about the interplay between defects in different fields—especially when they coevolve—within the same physical system. Here, using nematic microfluidics, we study the cross-talk of topological defects in two different material fields—the velocity field and the molecular orientational field. Specifically, we generate hydrodynamic stagnation points of different topological charges at the center of star-shaped microfluidic junctions, which then interact with emergent topological defects in the orientational field of the nematic director. We combine experiments and analytical and numerical calculations to show that a hydrodynamic singularity of a given topological charge can nucleate a nematic defect of equal topological charge and corroborate this by creating −1, −2, and −3 topological defects in four-, six-, and eight-arm junctions. Our work is an attempt toward understanding materials that are governed by distinctly multifield topology, where disparate topology-carrying fields are coupled and concertedly determine the material properties and response. PMID:28674012

AtomicChargeCalculator: interactive web-based calculation of atomic charges in large biomolecular complexes and drug-like molecules.

PubMed

Ionescu, Crina-Maria; Sehnal, David; Falginella, Francesco L; Pant, Purbaj; Pravda, Lukáš; Bouchal, Tomáš; Svobodová Vařeková, Radka; Geidl, Stanislav; Koča, Jaroslav

2015-01-01

Partial atomic charges are a well-established concept, useful in understanding and modeling the chemical behavior of molecules, from simple compounds, to large biomolecular complexes with many reactive sites. This paper introduces AtomicChargeCalculator (ACC), a web-based application for the calculation and analysis of atomic charges which respond to changes in molecular conformation and chemical environment. ACC relies on an empirical method to rapidly compute atomic charges with accuracy comparable to quantum mechanical approaches. Due to its efficient implementation, ACC can handle any type of molecular system, regardless of size and chemical complexity, from drug-like molecules to biomacromolecular complexes with hundreds of thousands of atoms. ACC writes out atomic charges into common molecular structure files, and offers interactive facilities for statistical analysis and comparison of the results, in both tabular and graphical form. Due to high customizability and speed, easy streamlining and the unified platform for calculation and analysis, ACC caters to all fields of life sciences, from drug design to nanocarriers. ACC is freely available via the Internet at http://ncbr.muni.cz/ACC.

Spin canting in a Dy-based single-chain magnet with dominant next-nearest-neighbor antiferromagnetic interactions

NASA Astrophysics Data System (ADS)

Bernot, K.; Luzon, J.; Caneschi, A.; Gatteschi, D.; Sessoli, R.; Bogani, L.; Vindigni, A.; Rettori, A.; Pini, M. G.

2009-04-01

We investigate theoretically and experimentally the static magnetic properties of single crystals of the molecular-based single-chain magnet of formula [Dy(hfac)3NIT(C6H4OPh)]∞ comprising alternating Dy3+ and organic radicals. The magnetic molar susceptibility χM displays a strong angular variation for sample rotations around two directions perpendicular to the chain axis. A peculiar inversion between maxima and minima in the angular dependence of χM occurs on increasing temperature. Using information regarding the monomeric building block as well as an ab initio estimation of the magnetic anisotropy of the Dy3+ ion, this “anisotropy-inversion” phenomenon can be assigned to weak one-dimensional ferromagnetism along the chain axis. This indicates that antiferromagnetic next-nearest-neighbor interactions between Dy3+ ions dominate, despite the large Dy-Dy separation, over the nearest-neighbor interactions between the radicals and the Dy3+ ions. Measurements of the field dependence of the magnetization, both along and perpendicularly to the chain, and of the angular dependence of χM in a strong magnetic field confirm such an interpretation. Transfer-matrix simulations of the experimental measurements are performed using a classical one-dimensional spin model with antiferromagnetic Heisenberg exchange interaction and noncollinear uniaxial single-ion anisotropies favoring a canted antiferromagnetic spin arrangement, with a net magnetic moment along the chain axis. The fine agreement obtained with experimental data provides estimates of the Hamiltonian parameters, essential for further study of the dynamics of rare-earth-based molecular chains.

Genetic control of root growth: from genes to networks

PubMed Central

Slovak, Radka; Ogura, Takehiko; Satbhai, Santosh B.; Ristova, Daniela; Busch, Wolfgang

2016-01-01

Background Roots are essential organs for higher plants. They provide the plant with nutrients and water, anchor the plant in the soil, and can serve as energy storage organs. One remarkable feature of roots is that they are able to adjust their growth to changing environments. This adjustment is possible through mechanisms that modulate a diverse set of root traits such as growth rate, diameter, growth direction and lateral root formation. The basis of these traits and their modulation are at the cellular level, where a multitude of genes and gene networks precisely regulate development in time and space and tune it to environmental conditions. Scope This review first describes the root system and then presents fundamental work that has shed light on the basic regulatory principles of root growth and development. It then considers emerging complexities and how they have been addressed using systems-biology approaches, and then describes and argues for a systems-genetics approach. For reasons of simplicity and conciseness, this review is mostly limited to work from the model plant Arabidopsis thaliana, in which much of the research in root growth regulation at the molecular level has been conducted. Conclusions While forward genetic approaches have identified key regulators and genetic pathways, systems-biology approaches have been successful in shedding light on complex biological processes, for instance molecular mechanisms involving the quantitative interaction of several molecular components, or the interaction of large numbers of genes. However, there are significant limitations in many of these methods for capturing dynamic processes, as well as relating these processes to genotypic and phenotypic variation. The emerging field of systems genetics promises to overcome some of these limitations by linking genotypes to complex phenotypic and molecular data using approaches from different fields, such as genetics, genomics, systems biology and phenomics. PMID:26558398

Self-consistent-field study of conduction through conjugated molecules

NASA Astrophysics Data System (ADS)

Paulsson, Magnus; Stafström, Sven

2001-07-01

Current-voltage (I-V) characteristics of individual molecules connected by metallic leads are studied theoretically. Using the Pariser-Parr-Pople quantum chemical method to model the molecule enables us to include electron-electron interactions in the Hartree approximation. The self-consistent-field method is used to calculate charging together with other properties for the total system under bias. Thereafter the Landauer formula is used to calculate the current from the transmission amplitudes. The most important parameter to understand charging is the position of the chemical potentials of the leads in relation to the molecular levels. At finite bias, the main part of the potential drop is located at the molecule-lead junctions. Also, the potential of the molecule is shown to partially follow the chemical potential closest to the highest occupied molecular orbital (HOMO). Therefore, the resonant tunneling steps in the I-V curves are smoothed giving a I-V resembling a ``Coulomb-gap.'' However, the charge of the molecule is not quantized since the molecule is small with quite strong interactions with the leads. The calculations predict an increase in the current at the bias corresponding to the energy gap of the molecule irrespective of the metals used in the leads. When the bias is increased further, charge is redistributed from the HOMO level to the lowest unoccupied molecular orbital of the molecule. This gives a step in the I-V curves and a corresponding change in the potential profile over the molecule. Calculations were mainly performed on polyene molecules. Molecules asymmetrically coupled to the leads model the I-V curves for molecules contacted by a scanning tunneling microscopy tip. I-V curves for pentapyrrole and another molecule that show negative differential conductance are also analyzed. The charging of these two systems depends on the shape of the molecular wave functions.

Nonlinear two-dimensional terahertz photon echo and rotational spectroscopy in the gas phase.

PubMed

Lu, Jian; Zhang, Yaqing; Hwang, Harold Y; Ofori-Okai, Benjamin K; Fleischer, Sharly; Nelson, Keith A

2016-10-18

Ultrafast 2D spectroscopy uses correlated multiple light-matter interactions for retrieving dynamic features that may otherwise be hidden under the linear spectrum; its extension to the terahertz regime of the electromagnetic spectrum, where a rich variety of material degrees of freedom reside, remains an experimental challenge. We report a demonstration of ultrafast 2D terahertz spectroscopy of gas-phase molecular rotors at room temperature. Using time-delayed terahertz pulse pairs, we observe photon echoes and other nonlinear signals resulting from molecular dipole orientation induced by multiple terahertz field-dipole interactions. The nonlinear time domain orientation signals are mapped into the frequency domain in 2D rotational spectra that reveal J-state-resolved nonlinear rotational dynamics. The approach enables direct observation of correlated rotational transitions and may reveal rotational coupling and relaxation pathways in the ground electronic and vibrational state.

Carbon Nanotube Based Groundwater Remediation: The Case of Trichloroethylene.

PubMed

Jha, Kshitij C; Liu, Zhuonan; Vijwani, Hema; Nadagouda, Mallikarjuna; Mukhopadhyay, Sharmila M; Tsige, Mesfin

2016-07-21

Adsorption of chlorinated organic contaminants (COCs) on carbon nanotubes (CNTs) has been gaining ground as a remedial platform for groundwater treatment. Applications depend on our mechanistic understanding of COC adsorption on CNTs. This paper lays out the nature of competing interactions at play in hybrid, membrane, and pure CNT based systems and presents results with the perspective of existing gaps in design strategies. First, current remediation approaches to trichloroethylene (TCE), the most ubiquitous of the COCs, is presented along with examination of forces contributing to adsorption of analogous contaminants at the molecular level. Second, we present results on TCE adsorption and remediation on pure and hybrid CNT systems with a stress on the specific nature of substrate and molecular architecture that would contribute to competitive adsorption. The delineation of intermolecular interactions that contribute to efficient remediation is needed for custom, scalable field design of purification systems for a wide range of contaminants.

Insight into the C-F bond mechanism of molecular analogs for antibacterial drug design.

PubMed

Liu, Junna; Lv, Biyu; Liu, Huaqing; Li, Xin; Yin, Weiping

2018-06-01

The activities of biological molecules usually rely on both of intra-molecular and intermolecular interactions between their function groups. These interactions include interonic attraction theory, Van der Waal's forces and the function of geometry on the individual molecules, whether they are naturally or synthetic. The purpose of this study was to evaluate the antibacterial activity of C-F bond compound using combination of experiments verification and theoretical calculation. We target on the insect natural products from the maggots of Chrysomyis megacephala Fabricius. Based on density functional theory(DFT) and B3LYP method, a theoretical study of the C-F bond on fluoride was designed to explore compounds 2 and 4 antibacterial structure-activity relationship. With the progress in DFT, first-principle calculation based on DFT has gradually become a routine method for drug design, quantum chemistry and other science fields.

Lattice dynamical and dielectric properties of L-amino acids

NASA Astrophysics Data System (ADS)

Tulip, P. R.; Clark, S. J.

2006-08-01

We present the results of ab initio calculations of the lattice dynamical and dielectric properties of the L-amino acids L-alanine, L-leucine, and L-isoleucine. Normal-mode frequencies and dielectric permittivity tensors are obtained using density-functional perturbation theory implemented within the plane-wave pseudopotential approximation. IR spectra are calculated and are used to analyze the effects of intermolecular interactions and zwitterionization upon the lattice dynamics. It is found that vibronic modes associated with the carboxy and amino functional groups undergo modification from their free-molecule values due to the presence of hydrogen bonds. The role of macroscopic electric fields set up by zone-center normal modes in the lattice dynamics is investigated by analysis of the Born effective charge. Calculated permittivity tensors are found to be greater than would be obtained by a naive use of the isolated molecular values, indicating the role of intermolecular interactions in increasing molecular polarizability.

Nuclear quadrupole resonance lineshape analysis for different motional models: Stochastic Liouville approach

NASA Astrophysics Data System (ADS)

Kruk, D.; Earle, K. A.; Mielczarek, A.; Kubica, A.; Milewska, A.; Moscicki, J.

2011-12-01

A general theory of lineshapes in nuclear quadrupole resonance (NQR), based on the stochastic Liouville equation, is presented. The description is valid for arbitrary motional conditions (particularly beyond the valid range of perturbation approaches) and interaction strengths. It can be applied to the computation of NQR spectra for any spin quantum number and for any applied magnetic field. The treatment presented here is an adaptation of the "Swedish slow motion theory," [T. Nilsson and J. Kowalewski, J. Magn. Reson. 146, 345 (2000), 10.1006/jmre.2000.2125] originally formulated for paramagnetic systems, to NQR spectral analysis. The description is formulated for simple (Brownian) diffusion, free diffusion, and jump diffusion models. The two latter models account for molecular cooperativity effects in dense systems (such as liquids of high viscosity or molecular glasses). The sensitivity of NQR slow motion spectra to the mechanism of the motional processes modulating the nuclear quadrupole interaction is discussed.

Molecular Ecology of Hypersaline Microbial Mats: Current Insights and New Directions.

PubMed

Wong, Hon Lun; Ahmed-Cox, Aria; Burns, Brendan Paul

2016-01-05

Microbial mats are unique geobiological ecosystems that form as a result of complex communities of microorganisms interacting with each other and their physical environment. Both the microorganisms present and the network of metabolic interactions govern ecosystem function therein. These systems are often found in a range of extreme environments, and those found in elevated salinity have been particularly well studied. The purpose of this review is to briefly describe the molecular ecology of select model hypersaline mat systems (Guerrero Negro, Shark Bay, S'Avall, and Kiritimati Atoll), and any potentially modulating effects caused by salinity to community structure. In addition, we discuss several emerging issues in the field (linking function to newly discovered phyla and microbial dark matter), which illustrate the changing paradigm that is seen as technology has rapidly advanced in the study of these extreme and evolutionally significant ecosystems.

Sig2BioPAX: Java tool for converting flat files to BioPAX Level 3 format.

PubMed

Webb, Ryan L; Ma'ayan, Avi

2011-03-21

The World Wide Web plays a critical role in enabling molecular, cell, systems and computational biologists to exchange, search, visualize, integrate, and analyze experimental data. Such efforts can be further enhanced through the development of semantic web concepts. The semantic web idea is to enable machines to understand data through the development of protocol free data exchange formats such as Resource Description Framework (RDF) and the Web Ontology Language (OWL). These standards provide formal descriptors of objects, object properties and their relationships within a specific knowledge domain. However, the overhead of converting datasets typically stored in data tables such as Excel, text or PDF into RDF or OWL formats is not trivial for non-specialists and as such produces a barrier to seamless data exchange between researchers, databases and analysis tools. This problem is particularly of importance in the field of network systems biology where biochemical interactions between genes and their protein products are abstracted to networks. For the purpose of converting biochemical interactions into the BioPAX format, which is the leading standard developed by the computational systems biology community, we developed an open-source command line tool that takes as input tabular data describing different types of molecular biochemical interactions. The tool converts such interactions into the BioPAX level 3 OWL format. We used the tool to convert several existing and new mammalian networks of protein interactions, signalling pathways, and transcriptional regulatory networks into BioPAX. Some of these networks were deposited into PathwayCommons, a repository for consolidating and organizing biochemical networks. The software tool Sig2BioPAX is a resource that enables experimental and computational systems biologists to contribute their identified networks and pathways of molecular interactions for integration and reuse with the rest of the research community.

Interactive Molecular Graphics for Augmented Reality Using HoloLens.

PubMed

Müller, Christoph; Krone, Michael; Huber, Markus; Biener, Verena; Herr, Dominik; Koch, Steffen; Reina, Guido; Weiskopf, Daniel; Ertl, Thomas

2018-06-13

Immersive technologies like stereo rendering, virtual reality, or augmented reality (AR) are often used in the field of molecular visualisation. Modern, comparably lightweight and affordable AR headsets like Microsoft's HoloLens open up new possibilities for immersive analytics in molecular visualisation. A crucial factor for a comprehensive analysis of molecular data in AR is the rendering speed. HoloLens, however, has limited hardware capabilities due to requirements like battery life, fanless cooling and weight. Consequently, insights from best practises for powerful desktop hardware may not be transferable. Therefore, we evaluate the capabilities of the HoloLens hardware for modern, GPU-enabled, high-quality rendering methods for the space-filling model commonly used in molecular visualisation. We also assess the scalability for large molecular data sets. Based on the results, we discuss ideas and possibilities for immersive molecular analytics. Besides more obvious benefits like the stereoscopic rendering offered by the device, this specifically includes natural user interfaces that use physical navigation instead of the traditional virtual one. Furthermore, we consider different scenarios for such an immersive system, ranging from educational use to collaborative scenarios.

Radical-lanthanide ferromagnetic interaction in a T bIII bis-phthalocyaninato complex

NASA Astrophysics Data System (ADS)

Komijani, Dorsa; Ghirri, Alberto; Bonizzoni, Claudio; Klyatskaya, Svetlana; Moreno-Pineda, Eufemio; Ruben, Mario; Soncini, Alessandro; Affronte, Marco; Hill, Stephen

2018-02-01

Recent studies have highlighted the importance of organic ligands in the field of molecular spintronics, via which delocalized electron-spin density can mediate magnetic coupling to otherwise localized 4 f moments of lanthanide ions, which show tremendous potential for single-molecule device applications. To this end, high-field/high-frequency electron paramagnetic resonance (EPR) spectroscopy is employed to study a neutral terbium bis-phthalocyaninato metalorganic complex, [TbPc2 ] 0, with the aim of understanding the magnetic interaction between the Ising-like moment of the lanthanide ion and the unpaired spin density on the coordinating organic radical ligand. The measurements were performed on a previously unknown [TbPc2 ] 0 structural phase crystallizing in the Pnma space group. EPR measurements on powder samples of [TbPc2 ] 0 reveal an anisotropic spectrum, which is attributed to the spin-1/2 radical coupled weakly to the EPR-silent T bIII ion. Extensive double-axis rotation studies on a single crystal reveal two independent spin-1/2 signals with differently oriented (albeit identical) uniaxial g -tensors, in complete agreement with x-ray structural studies that indicate two molecular orientations within the unit cell. The easy-axis nature of the radical EPR spectra thus reflects the coupling to the Ising-like T bIII moment. This is corroborated by studies of the isostructural [YPc2 ] 0 analog (where Y is nonmagnetic yttrium), which gives a completely isotropic radical EPR signal. The experimental results for the terbium complex are well explained on the basis of an effective model that introduces a weak ferromagnetic Heisenberg coupling between an isotropic spin-1/2 and an anisotropic spin-orbital moment, J =6 , that mimics the known, strong easy-axis Tb ⋯P c2 crystal-field interaction.

Molecular evidence of facultative intraguild predation by Monochamus titillator larvae (Coleoptera: Cerambycidae) on members of the southern pine beetle guild.

PubMed

Schoeller, Erich N; Husseneder, Claudia; Allison, Jeremy D

2012-11-01

The southern pine bark beetle guild (SPBG) is arguably the most destructive group of forest insects in the southeastern USA. This guild contains five species of bark beetles (Coleoptera: Curculionidae: Scolytinae): Dendroctonus frontalis, Dendroctonus terebrans, Ips avulsus, Ips calligraphus, and Ips grandicollis. A diverse community of illicit receivers is attracted to pheromones emitted by the SPBG, including the woodborers Monochamus carolinensis and Monochamus titillator (Coleoptera: Cerambycidae). These woodborers have been traditionally classified as resource competitors; however, laboratory assays suggest that larval M. carolinensis may be facultative intraguild predators of SPBG larvae. This study used polymerase chain reaction (PCR)-based molecular gut content analyses to characterize subcortical interactions between M. titillator and members of the SPBG. The half-lives of SPBG DNA were estimated in the laboratory prior to examining these interactions in the field. A total of 271 field-collected M. titillator larvae were analyzed and 26 (9.6 %) tested positive for DNA of members of the SPBG. Of these larvae, 25 (96.2 %) tested positive for I. grandicollis and one (3.8 %) for I. calligraphus. Failure to detect D. terebrans and D. frontalis was likely due to their absence in the field. I. avulsus was present, but primers developed using adult tissues failed to amplify larval tissue. Results from this study support the hypothesis that larval Monochamus spp. are facultative intraguild predators of bark beetle larvae. Additionally, this study demonstrates the capabilities of PCR in elucidating the interactions of cryptic forest insects and provides a tool to better understand mechanisms driving southern pine beetle guild population fluctuations.

Molecular dynamics of β-hairpin models of epigenetic recognition motifs.

PubMed

Zheng, Xiange; Wu, Chuanjie; Ponder, Jay W; Marshall, Garland R

2012-09-26

The conformations and stabilities of the β-hairpin model peptides of Waters (Riemen, A. J.; Waters, M. L. Biochemistry 2009, 48, 1525; Hughes, R. M.; Benshoff, M. L.; Waters, M. L. Chemistry 2007, 13, 5753) have been experimentally characterized as a function of lysine ε-methylation. These models were developed to explore molecular recognition of known epigenetic recognition motifs. This system offered an opportunity to computationally examine the role of cation-π interactions, desolvation of the ε-methylated ammonium groups, and aromatic/aromatic interactions on the observed differences in NMR spectra. AMOEBA, a second-generation force field (Ponder, J. W.; Wu, C.; Ren, P.; Pande, V. S.; Chodera, J. D.; Schnieders, M. J.; Haque, I.; Mobley, D. L.; Lambrecht, D. S.; DiStasio, R. A., Jr.; Head-Gordon, M.; Clark, G. N.; Johnson, M. E.; Head-Gordon, T. J. Phys. Chem. B 2010, 114, 2549), was chosen as it includes both multipole electrostatics and polarizability thought to be essential to accurately characterize such interactions. Independent parametrization of ε-methylated amines was required from which aqueous solvation free energies were estimated and shown to agree with literature values. Molecular dynamics simulations (100 ns) using the derived parameters with model peptides, such as Ac-R-W-V-W-V-N-G-Orn-K(Me)(n)-I-L-Q-NH(2), where n = 0, 1, 2, or 3, were conducted in explicit solvent. Distances between the centers of the indole rings of the two-tryptophan residues, 2 and 4, and the ε-methylated ammonium group on Lys-9 as well as the distance between the N- and C-termini were monitored to estimate the strength and orientation of the cation-π and aromatic/aromatic interactions. In agreement with the experimental data, the stability of the β-hairpin increased significantly with lysine ε-methylation. The ability of MD simulations to reproduce the observed NOEs for the four peptides was further estimated for the monopole-based force fields, AMBER, CHARMM, and OPLSAA. AMOEBA correctly predicted over 80% of the observed NOEs for all 4 peptides, while the three-monopole force fields were 40-50% predictive in only 2 cases and approximately 10% in the other 10 examples. Preliminary analysis suggests that the decreased cost of desolvation of the substituted ammonium group significantly compensated for the reduced cation-π interaction resulting from the increased separation due to steric bulk of the ε-methylated amines.

Soft matter interactions at the molecular scale: interaction forces and energies between single hydrophobic model peptides.

PubMed

Stock, Philipp; Utzig, Thomas; Valtiner, Markus

2017-02-08

In all realms of soft matter research a fundamental understanding of the structure/property relationships based on molecular interactions is crucial for developing a framework for the targeted design of soft materials. However, a molecular picture is often difficult to ascertain and yet essential for understanding the many different competing interactions at play, including entropies and cooperativities, hydration effects, and the enormous design space of soft matter. Here, we characterized for the first time the interaction between single hydrophobic molecules quantitatively using atomic force microscopy, and demonstrated that single molecular hydrophobic interaction free energies are dominated by the area of the smallest interacting hydrophobe. The interaction free energy amounts to 3-4 kT per hydrophobic unit. Also, we find that the transition state of the hydrophobic interactions is located at 3 Å with respect to the ground state, based on Bell-Evans theory. Our results provide a new path for understanding the nature of hydrophobic interactions at the single molecular scale. Our approach enables us to systematically vary hydrophobic and any other interaction type by utilizing peptide chemistry providing a strategic advancement to unravel molecular surface and soft matter interactions at the single molecular scale.

BMRF-Net: a software tool for identification of protein interaction subnetworks by a bagging Markov random field-based method.

PubMed

Shi, Xu; Barnes, Robert O; Chen, Li; Shajahan-Haq, Ayesha N; Hilakivi-Clarke, Leena; Clarke, Robert; Wang, Yue; Xuan, Jianhua

2015-07-15

Identification of protein interaction subnetworks is an important step to help us understand complex molecular mechanisms in cancer. In this paper, we develop a BMRF-Net package, implemented in Java and C++, to identify protein interaction subnetworks based on a bagging Markov random field (BMRF) framework. By integrating gene expression data and protein-protein interaction data, this software tool can be used to identify biologically meaningful subnetworks. A user friendly graphic user interface is developed as a Cytoscape plugin for the BMRF-Net software to deal with the input/output interface. The detailed structure of the identified networks can be visualized in Cytoscape conveniently. The BMRF-Net package has been applied to breast cancer data to identify significant subnetworks related to breast cancer recurrence. The BMRF-Net package is available at http://sourceforge.net/projects/bmrfcjava/. The package is tested under Ubuntu 12.04 (64-bit), Java 7, glibc 2.15 and Cytoscape 3.1.0. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Protein complexes, big data, machine learning and integrative proteomics: lessons learned over a decade of systematic analysis of protein interaction networks.

PubMed

Havugimana, Pierre C; Hu, Pingzhao; Emili, Andrew

2017-10-01

Elucidation of the networks of physical (functional) interactions present in cells and tissues is fundamental for understanding the molecular organization of biological systems, the mechanistic basis of essential and disease-related processes, and for functional annotation of previously uncharacterized proteins (via guilt-by-association or -correlation). After a decade in the field, we felt it timely to document our own experiences in the systematic analysis of protein interaction networks. Areas covered: Researchers worldwide have contributed innovative experimental and computational approaches that have driven the rapidly evolving field of 'functional proteomics'. These include mass spectrometry-based methods to characterize macromolecular complexes on a global-scale and sophisticated data analysis tools - most notably machine learning - that allow for the generation of high-quality protein association maps. Expert commentary: Here, we recount some key lessons learned, with an emphasis on successful workflows, and challenges, arising from our own and other groups' ongoing efforts to generate, interpret and report proteome-scale interaction networks in increasingly diverse biological contexts.

Magnetic properties of a quasi-two-dimensional S =1/2 Heisenberg antiferromagnet with distorted square lattice

NASA Astrophysics Data System (ADS)

Yamaguchi, Hironori; Tamekuni, Yusuke; Iwasaki, Yoshiki; Otsuka, Rei; Hosokoshi, Yuko; Kida, Takanori; Hagiwara, Masayuki

2017-06-01

We successfully synthesize single crystals of the verdazyl radical α -2 ,3 ,5 -Cl3 -V. Ab initio molecular orbital calculations indicate that the two dominant antiferromagnetic interactions, J1 and J2 (α =J2/J1≃0.56 ), form an S =1 /2 distorted square lattice. We explain the magnetic properties based on the S =1 /2 square lattice Heisenberg antiferromagnet using the quantum Monte Carlo method, and examine the effects of the lattice distortion and the interplane interaction contribution. In the low-temperature regions below 6.4 K, we observe anisotropic magnetic behavior accompanied by a phase transition to a magnetically ordered state. The electron spin resonance signals exhibit anisotropic behavior in the temperature dependence of the resonance field and the linewidth. We explain the frequency dependence of the resonance fields in the ordered phase using a mean-field approximation with out-of-plane easy-axis anisotropy, which causes a spin-flop phase transition at approximately 0.4 T for the field perpendicular to the plane. Furthermore, the anisotropic dipole field provides supporting information regarding the presence of the easy-axis anisotropy. These results demonstrate that the lattice distortion, anisotropy, and interplane interaction of this model are sufficiently small that they do not affect the intrinsic behavior of the S =1 /2 square lattice Heisenberg antiferromagnet.

Mean-field density functional theory of a nanoconfined classical, three-dimensional Heisenberg fluid. I. The role of molecular anchoring

NASA Astrophysics Data System (ADS)

Cattes, Stefanie M.; Gubbins, Keith E.; Schoen, Martin

2016-05-01

In this work, we employ classical density functional theory (DFT) to investigate for the first time equilibrium properties of a Heisenberg fluid confined to nanoscopic slit pores of variable width. Within DFT pair correlations are treated at modified mean-field level. We consider three types of walls: hard ones, where the fluid-wall potential becomes infinite upon molecular contact but vanishes otherwise, and hard walls with superimposed short-range attraction with and without explicit orientation dependence. To model the distance dependence of the attractions, we employ a Yukawa potential. The orientation dependence is realized through anchoring of molecules at the substrates, i.e., an energetic discrimination of specific molecular orientations. If the walls are hard or attractive without specific anchoring, the results are "quasi-bulk"-like in that they can be linked to a confinement-induced reduction of the bulk mean field. In these cases, the precise nature of the walls is completely irrelevant at coexistence. Only for specific anchoring nontrivial features arise, because then the fluid-wall interaction potential affects the orientation distribution function in a nontrivial way and thus appears explicitly in the Euler-Lagrange equations to be solved for minima of the grand potential of coexisting phases.

The Physics of Molecular Shocks in Star-Forming Regions

NASA Technical Reports Server (NTRS)

Hollenbach, David; Cuzzi, Jeffrey (Technical Monitor)

1996-01-01

Molecular shocks are produced by the impact of the supersonic infall of gas and dust onto protostars and by the interaction of the supersonic outflow from the protostar with the circumstellar material. Infalling gas creates an accretion shock around the circumstellar disk which emits a unique infrared spectrum and which processes the interstellar dust as it enters the disk. The winds and jets from protostars also impact the disk, the infalling material, and the ambient molecular cloud core creating shocks whose spectrum and morphology diagnose the mass loss processes of the protostar and the orientation and structure of the star forming system. We discuss the physics of these shocks, the model spectra derived from theoretical models, and comparisons with observations of H2O masers, H2 emission, as well as other shocks tracers. We show the strong effect of magnetic fields on molecular shock structure, and elucidate the chemical changes induced by the shock heating and compression.

Transitioning NWChem to the Next Generation of Manycore Machines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bylaska, Eric J.; Apra, Edoardo; Kowalski, Karol

The NorthWest Chemistry (NWChem) modeling software is a popular molecular chemistry simulation software that was designed from the start to work on massively parallel processing supercomputers[6, 28, 49]. It contains an umbrella of modules that today includes Self Consistent Field (SCF), second order Mller-Plesset perturbation theory (MP2), Coupled Cluster, multi-conguration selfconsistent eld (MCSCF), selected conguration interaction (CI), tensor contraction engine (TCE) many body methods, density functional theory (DFT), time-dependent density functional theory (TDDFT), real time time-dependent density functional theory, pseudopotential plane-wave density functional theory (PSPW), band structure (BAND), ab initio molecular dynamics, Car-Parrinello molecular dynamics, classical molecular dynamics (MD), QM/MM,more » AIMD/MM, GIAO NMR, COSMO, COSMO-SMD, and RISM solvation models, free energy simulations, reaction path optimization, parallel in time, among other capabilities[ 22]. Moreover new capabilities continue to be added with each new release.« less

Hybrid molecular-colloidal liquid crystals.

PubMed

Mundoor, Haridas; Park, Sungoh; Senyuk, Bohdan; Wensink, Henricus H; Smalyukh, Ivan I

2018-05-18

Order and fluidity often coexist, with examples ranging from biological membranes to liquid crystals, but the symmetry of these soft-matter systems is typically higher than that of the constituent building blocks. We dispersed micrometer-long inorganic colloidal rods in a nematic liquid crystalline fluid of molecular rods. Both types of uniaxial building blocks, while freely diffusing, interact to form an orthorhombic nematic fluid, in which like-sized rods are roughly parallel to each other and the molecular ordering direction is orthogonal to that of colloidal rods. A coarse-grained model explains the experimental temperature-concentration phase diagram with one biaxial and two uniaxial nematic phases, as well as the orientational distributions of rods. Displaying properties of biaxial optical crystals, these hybrid molecular-colloidal fluids can be switched by electric and magnetic fields. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Two-dimensional infrared spectroscopy of vibrational polaritons.

PubMed

Xiang, Bo; Ribeiro, Raphael F; Dunkelberger, Adam D; Wang, Jiaxi; Li, Yingmin; Simpkins, Blake S; Owrutsky, Jeffrey C; Yuen-Zhou, Joel; Xiong, Wei

2018-05-08

We report experimental 2D infrared (2D IR) spectra of coherent light-matter excitations--molecular vibrational polaritons. The application of advanced 2D IR spectroscopy to vibrational polaritons challenges and advances our understanding in both fields. First, the 2D IR spectra of polaritons differ drastically from free uncoupled excitations and a new interpretation is needed. Second, 2D IR uniquely resolves excitation of hybrid light-matter polaritons and unexpected dark states in a state-selective manner, revealing otherwise hidden interactions between them. Moreover, 2D IR signals highlight the impact of molecular anharmonicities which are applicable to virtually all molecular systems. A quantum-mechanical model is developed which incorporates both nuclear and electrical anharmonicities and provides the basis for interpreting this class of 2D IR spectra. This work lays the foundation for investigating phenomena of nonlinear photonics and chemistry of molecular vibrational polaritons which cannot be probed with traditional linear spectroscopy.

Molecular engineering of antibodies for therapeutic and diagnostic purposes

PubMed Central

Ducancel, Frédéric; Muller, Bruno H.

2012-01-01

During the past ten years, monoclonal antibodies (mAbs) have taken center stage in the field of targeted therapy and diagnosis. This increased interest in mAbs is due to their binding accuracy (affinity and specificity) together with the original molecular and structural rules that govern interactions with their cognate antigen. In addition, the effector properties of antibodies constitute a second major advantage associated with their clinical use. The development of molecular and structural engineering and more recently of in vitro evolution of antibodies has opened up new perspectives in the de novo design of antibodies more adapted to clinical and diagnostic use. Thus, efforts are regularly made by researchers to improve or modulate antibody recognition properties, to adapt their pharmacokinetics, engineer their stability, and control their immunogenicity. This review presents the latest molecular engineering results on mAbs with therapeutic and diagnostic applications. PMID:22684311

Binding site exploration of CCR5 using in silico methodologies: a 3D-QSAR approach.

PubMed

Gadhe, Changdev G; Kothandan, Gugan; Cho, Seung Joo

2013-01-01

Chemokine receptor 5 (CCR5) is an important receptor used by human immunodeficiency virus type 1 (HIV-1) to gain viral entry into host cell. In this study, we used a combined approach of comparative modeling, molecular docking, and three dimensional quantitative structure activity relationship (3D-QSAR) analyses to elucidate detailed interaction of CCR5 with their inhibitors. Docking study of the most potent inhibitor from a series of compounds was done to derive the bioactive conformation. Parameters such as random selection, rational selection, different charges and grid spacing were utilized in the model development to check their performance on the model predictivity. Final comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were chosen based on the rational selection method, Gasteiger-Hückel charges and a grid spacing of 0.5 Å. Rational model for CoMFA (q(2) = 0.722, r(2) = 0.884, Q(2) = 0.669) and CoMSIA (q(2) = 0.712, r(2) = 0.825, Q(2) = 0.522) was obtained with good statistics. Mapping of contour maps onto CCR5 interface led us to better understand of the ligand-protein interaction. Docking analysis revealed that the Glu283 is crucial for interaction. Two new amino acid residues, Tyr89 and Thr167 were identified as important in ligand-protein interaction. No site directed mutagenesis studies on these residues have been reported.

Modeling of molecular diffusion and thermal conduction with multi-particle interaction in compressible turbulence

NASA Astrophysics Data System (ADS)

Tai, Y.; Watanabe, T.; Nagata, K.

2018-03-01

A mixing volume model (MVM) originally proposed for molecular diffusion in incompressible flows is extended as a model for molecular diffusion and thermal conduction in compressible turbulence. The model, established for implementation in Lagrangian simulations, is based on the interactions among spatially distributed notional particles within a finite volume. The MVM is tested with the direct numerical simulation of compressible planar jets with the jet Mach number ranging from 0.6 to 2.6. The MVM well predicts molecular diffusion and thermal conduction for a wide range of the size of mixing volume and the number of mixing particles. In the transitional region of the jet, where the scalar field exhibits a sharp jump at the edge of the shear layer, a smaller mixing volume is required for an accurate prediction of mean effects of molecular diffusion. The mixing time scale in the model is defined as the time scale of diffusive effects at a length scale of the mixing volume. The mixing time scale is well correlated for passive scalar and temperature. Probability density functions of the mixing time scale are similar for molecular diffusion and thermal conduction when the mixing volume is larger than a dissipative scale because the mixing time scale at small scales is easily affected by different distributions of intermittent small-scale structures between passive scalar and temperature. The MVM with an assumption of equal mixing time scales for molecular diffusion and thermal conduction is useful in the modeling of the thermal conduction when the modeling of the dissipation rate of temperature fluctuations is difficult.

Spin interactions in InAs quantum dots

NASA Astrophysics Data System (ADS)

Doty, M. F.; Ware, M. E.; Stinaff, E. A.; Scheibner, M.; Bracker, A. S.; Gammon, D.; Ponomarev, I. V.; Reinecke, T. L.; Korenev, V. L.

2006-03-01

Fine structure splittings in optical spectra of self-assembled InAs quantum dots (QDs) generally arise from spin interactions between particles confined in the dots. We present experimental studies of the fine structure that arises from multiple charges confined in a single dot [1] or in molecular orbitals of coupled pairs of dots. To probe the underlying spin interactions we inject particles with a known spin orientation (by using polarized light to perform photoluminescence excitation spectroscopy experiments) or use a magnetic field to orient and/or mix the spin states. We develop a model of the spin interactions that aids in the development of quantum information processing applications based on controllable interactions between spins confined to QDs. [1] Polarized Fine Structure in the Photoluminescence Excitation Spectrum of a Negatively Charged Quantum Dot, Phys. Rev. Lett. 95, 177403 (2005)

Comparison of Chain Conformation of Poly(vinyl alcohol) in Solutions and Melts from Quantum Chemistry Based Molecular Dynamics Simulations

NASA Technical Reports Server (NTRS)

Jaffe, Richard; Han, Jie; Matsuda, Tsunetoshi; Yoon, Do; Langhoff, Stephen R. (Technical Monitor)

1997-01-01

Confirmations of 2,4-dihydroxypentane (DHP), a model molecule for poly(vinyl alcohol), have been studied by quantum chemistry (QC) calculations and molecular dynamics (MD) simulations. QC calculations at the 6-311G MP2 level show the meso tt conformer to be lowest in energy followed by the racemic tg, due to intramolecular hydrogen bond between the hydroxy groups. The Dreiding force field has been modified to reproduce the QC conformer energies for DHP. MD simulations using this force field have been carried out for DHP molecules in the gas phase, melt, and CHCl3 and water solutions. Extensive intramolecular hydrogen bonding is observed for the gas phase and CHCl3 solution, but not for the melt or aqueous solution, Such a condensed phase effect due to intermolecular interactions results in a drastic change in chain conformations, in agreement with experiments.

Ultrafast and nonlinear surface-enhanced Raman spectroscopy.

PubMed

Gruenke, Natalie L; Cardinal, M Fernanda; McAnally, Michael O; Frontiera, Renee R; Schatz, George C; Van Duyne, Richard P

2016-04-21

Ultrafast surface-enhanced Raman spectroscopy (SERS) has the potential to study molecular dynamics near plasmonic surfaces to better understand plasmon-mediated chemical reactions such as plasmonically-enhanced photocatalytic or photovoltaic processes. This review discusses the combination of ultrafast Raman spectroscopic techniques with plasmonic substrates for high temporal resolution, high sensitivity, and high spatial resolution vibrational spectroscopy. First, we introduce background information relevant to ultrafast SERS: the mechanisms of surface enhancement in Raman scattering, the characterization of plasmonic materials with ultrafast techniques, and early complementary techniques to study molecule-plasmon interactions. We then discuss recent advances in surface-enhanced Raman spectroscopies with ultrafast pulses with a focus on the study of molecule-plasmon coupling and molecular dynamics with high sensitivity. We also highlight the challenges faced by this field by the potential damage caused by concentrated, highly energetic pulsed fields in plasmonic hotspots, and finally the potential for future ultrafast SERS studies.

Nonlinear terahertz coherent excitation of vibrational modes of liquids.

PubMed

Allodi, Marco A; Finneran, Ian A; Blake, Geoffrey A

2015-12-21

We report the first coherent excitation of intramolecular vibrational modes via the nonlinear interaction of a TeraHertz (THz) light field with molecular liquids. A terahertz-terahertz-Raman pulse sequence prepares the coherences with a broadband, high-energy, (sub)picosecond terahertz pulse, that are then measured in a terahertz Kerr effect spectrometer via phase-sensitive, heterodyne detection with an optical pulse. The spectrometer reported here has broader terahertz frequency coverage, and an increased sensitivity relative to previously reported terahertz Kerr effect experiments. Vibrational coherences are observed in liquid diiodomethane at 3.66 THz (122 cm(-1)), and in carbon tetrachloride at 6.50 THz (217 cm(-1)), in exact agreement with literature values of those intramolecular modes. This work opens the door to 2D spectroscopies, nonlinear in terahertz field, that can study the dynamics of condensed-phase molecular systems, as well as coherent control at terahertz frequencies.

Development of a Polarizable Force Field for Molecular Dynamics Simulations of Poly (Ethylene Oxide) in Aqueous Solution.

PubMed

Starovoytov, Oleg N; Borodin, Oleg; Bedrov, Dmitry; Smith, Grant D

2011-06-14

We have developed a quantum chemistry-based polarizable potential for poly(ethylene oxide) (PEO) in aqueous solution based on the APPLE&P polarizable ether and the SWM4-DP polarizable water models. Ether-water interactions were parametrized to reproduce the binding energy of water with 1,2-dimethoxyethane (DME) determined from high-level quantum chemistry calculations. Simulations of DME-water and PEO-water solutions at room temperature using the new polarizable potentials yielded thermodynamic properties in good agreement with experimental results. The predicted miscibility of PEO and water as a function of the temperature was found to be strongly correlated with the predicted free energy of solvation of DME. The developed nonbonded force field parameters were found to be transferrable to poly(propylene oxide) (PPO), as confirmed by capturing, at least qualitatively, the miscibility of PPO in water as a function of the molecular weight.

Application of epigenetic markers in molecular breeding of the swine.

PubMed

Zhang, Ke; Feng, Guang-de; Zhang, Bao-yun; Xiang, Wei; Chen, Long; Yang, Fang; Chu, Ming-xing; Wang, Ping-qing

2016-07-20

Livestock phenotypes are determined by the interaction of a variety of factors, including the genome, the epigenome and the environment. Epigenetics refers to gene expression changes without DNA sequence alterations. Epigenetic markers mainly include DNA methylation, histone modifications, non-coding RNAs, and imprinting genes. More and more researches show that epigenetic markers play an important role in the traits of pigs by modulating phenotype changes via gene expression. However, the role of epigenetic markers has caught little attention in swine breeding. The mechanism that influences important traits of swine has not been analyzed in detail, and it still lacks adequate scientific basis for practical applications. From the aspects of nutrition, diseases, important economic traits and trans-generational inheritance, we summarize the research, application prospects and challenges in the field of utilizing epigenetic markers in molecular breeding of pigs, thus providing a more comprehensive theoretical basis to promote more rapid research development in this field.

Excitation and decay of aluminum bulk plasmons at the aluminum/copper phthalocyanine interface

NASA Astrophysics Data System (ADS)

Di Filippo, Gianluca; Sbroscia, Marco; Stefani, Giovanni; Bartynski, Robert A.; Ruocco, Alessandro

2018-06-01

We present the results of an experiment aimed at studying the archetypal properties of the aluminum bulk plasmon at an organic/metal interface. Electron-electron coincidence spectroscopy is used to determine the contribution of aluminum bulk plasmon decay to the ionization of a thin copper phthalocyanine film. The latter directly depends on the amplitude of the bulk plasmon electric field (generated in the metal substrate) protruding inside the molecular overlayer. The emission of low-energy electrons from the clean substrate is dominated by plasmon-assisted ionization events. These events are not observed when the molecules are adsorbed onto the surface. Our findings suggest that, for the considered system, the bulk plasmon wave is confined within the medium in which it is generated and the interaction of the plasmon field with electrons located in the molecular overlayer does not lead to the emission of low-energy electrons.

Probing long-range carrier-pair spin–spin interactions in a conjugated polymer by detuning of electrically detected spin beating

PubMed Central

van Schooten, Kipp J.; Baird, Douglas L.; Limes, Mark E.; Lupton, John M.; Boehme, Christoph

2015-01-01

Weakly coupled electron spin pairs that experience weak spin–orbit interaction can control electronic transitions in molecular and solid-state systems. Known to determine radical pair reactions, they have been invoked to explain phenomena ranging from avian magnetoreception to spin-dependent charge-carrier recombination and transport. Spin pairs exhibit persistent spin coherence, allowing minute magnetic fields to perturb spin precession and thus recombination rates and photoreaction yields, giving rise to a range of magneto-optoelectronic effects in devices. Little is known, however, about interparticle magnetic interactions within such pairs. Here we present pulsed electrically detected electron spin resonance experiments on poly(styrene-sulfonate)-doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) devices, which show how interparticle spin–spin interactions (magnetic-dipolar and spin-exchange) between charge-carrier spin pairs can be probed through the detuning of spin-Rabi oscillations. The deviation from uncoupled precession frequencies quantifies both the exchange (<30 neV) and dipolar (23.5±1.5 neV) interaction energies responsible for the pair's zero-field splitting, implying quantum mechanical entanglement of charge-carrier spins over distances of 2.1±0.1 nm. PMID:25868686

Probing long-range carrier-pair spin–spin interactions in a conjugated polymer by detuning of electrically detected spin beating

DOE PAGES

van Schooten, Kipp J.; Baird, Douglas L.; Limes, Mark E.; ...

2015-04-14

Here, weakly coupled electron spin pairs that experience weak spin–orbit interaction can control electronic transitions in molecular and solid-state systems. Known to determine radical pair reactions, they have been invoked to explain phenomena ranging from avian magnetoreception to spin-dependent charge-carrier recombination and transport. Spin pairs exhibit persistent spin coherence, allowing minute magnetic fields to perturb spin precession and thus recombination rates and photoreaction yields, giving rise to a range of magneto-optoelectronic effects in devices. Little is known, however, about interparticle magnetic interactions within such pairs. Here we present pulsed electrically detected electron spin resonance experiments on poly(styrene-sulfonate)-doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) devices,more » which show how interparticle spin–spin interactions (magnetic-dipolar and spin-exchange) between charge-carrier spin pairs can be probed through the detuning of spin-Rabi oscillations. The deviation from uncoupled precession frequencies quantifies both the exchange (<30 neV) and dipolar (23.5±1.5 neV) interaction energies responsible for the pair’s zero-field splitting, implying quantum mechanical entanglement of charge-carrier spins over distances of 2.1±0.1 nm.« less

Biotic interactions as drivers of algal origin and evolution.

PubMed

Brodie, Juliet; Ball, Steven G; Bouget, François-Yves; Chan, Cheong Xin; De Clerck, Olivier; Cock, J Mark; Gachon, Claire; Grossman, Arthur R; Mock, Thomas; Raven, John A; Saha, Mahasweta; Smith, Alison G; Vardi, Assaf; Yoon, Hwan Su; Bhattacharya, Debashish

2017-11-01

Contents 670 I. 671 II. 671 III. 676 IV. 678 678 References 678 SUMMARY: Biotic interactions underlie life's diversity and are the lynchpin to understanding its complexity and resilience within an ecological niche. Algal biologists have embraced this paradigm, and studies building on the explosive growth in omics and cell biology methods have facilitated the in-depth analysis of nonmodel organisms and communities from a variety of ecosystems. In turn, these advances have enabled a major revision of our understanding of the origin and evolution of photosynthesis in eukaryotes, bacterial-algal interactions, control of massive algal blooms in the ocean, and the maintenance and degradation of coral reefs. Here, we review some of the most exciting developments in the field of algal biotic interactions and identify challenges for scientists in the coming years. We foresee the development of an algal knowledgebase that integrates ecosystem-wide omics data and the development of molecular tools/resources to perform functional analyses of individuals in isolation and in populations. These assets will allow us to move beyond mechanistic studies of a single species towards understanding the interactions amongst algae and other organisms in both the laboratory and the field. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Ferrotoroidic ground state in a heterometallic {CrIIIDyIII6} complex displaying slow magnetic relaxation.

PubMed

Vignesh, Kuduva R; Soncini, Alessandro; Langley, Stuart K; Wernsdorfer, Wolfgang; Murray, Keith S; Rajaraman, Gopalan

2017-10-18

Toroidal quantum states are most promising for building quantum computing and information storage devices, as they are insensitive to homogeneous magnetic fields, but interact with charge and spin currents, allowing this moment to be manipulated purely by electrical means. Coupling molecular toroids into larger toroidal moments via ferrotoroidic interactions can be pivotal not only to enhance ground state toroidicity, but also to develop materials displaying ferrotoroidic ordered phases, which sustain linear magneto-electric coupling and multiferroic behavior. However, engineering ferrotoroidic coupling is known to be a challenging task. Here we have isolated a {Cr III Dy III 6 } complex that exhibits the much sought-after ferrotoroidic ground state with an enhanced toroidal moment, solely arising from intramolecular dipolar interactions. Moreover, a theoretical analysis of the observed sub-Kelvin zero-field hysteretic spin dynamics of {Cr III Dy III 6 } reveals the pivotal role played by ferrotoroidic states in slowing down the magnetic relaxation, in spite of large calculated single-ion quantum tunneling rates.

Subsystem density-functional theory as an effective tool for modeling ground and excited states, their dynamics and many-body interactions.

PubMed

Krishtal, Alisa; Sinha, Debalina; Genova, Alessandro; Pavanello, Michele

2015-05-13

Subsystem density-functional theory (DFT) is an emerging technique for calculating the electronic structure of complex molecular and condensed phase systems. In this topical review, we focus on some recent advances in this field related to the computation of condensed phase systems, their excited states, and the evaluation of many-body interactions between the subsystems. As subsystem DFT is in principle an exact theory, any advance in this field can have a dual role. One is the possible applicability of a resulting method in practical calculations. The other is the possibility of shedding light on some quantum-mechanical phenomenon which is more easily treated by subdividing a supersystem into subsystems. An example of the latter is many-body interactions. In the discussion, we present some recent work from our research group as well as some new results, casting them in the current state-of-the-art in this review as comprehensively as possible.

π -Stacking interactions in YFP, quantum mechanics and force field evaluations in the S0 and S1 states

NASA Astrophysics Data System (ADS)

Merabti, Karim Elhadj; Azizi, Sihem; Ridard, Jacqueline; Lévy, Bernard; Demachy, Isabelle

2017-08-01

We study the π -stacking interaction between the chromophore and Tyr203 in the Yellow Fluorescent Protein (YFP) in order to (i) evaluate the contribution of the internal interaction energy of the isolated Chromophore-Tyrosine complex (Eint) to the 26 nm red shift observed from GFP to YFP, (ii) compare the effects of Eint and of the proteic environment. To that end, we perform quantum mechanical and force field (ff) calculations of the isolated complex in S0 and S1 states on a large sample of geometries, together with molecular dynamics simulations and potential of mean force analysis. The calculated absorption wavelengths are found red shifted with respect to the isolated chromophore by 12-19 nm, that represents a large part of the GFP-YFP shift. We find that the effect of the protein is determinant on the dynamics of the complex while the error that results from using a classicalff is of limited effect.

Phenolic Polymer Solvation in Water and Ethylene Glycol, II: Ab Initio Computations.

PubMed

Bauschlicher, Charles W; Bucholz, Eric W; Haskins, Justin B; Monk, Joshua D; Lawson, John W

2017-04-06

Ab initio techniques are used to study the interaction of ethylene glycol and water with a phenolic polymer. The water bonds more strongly with the phenolic OH than with the ring. The phenolic OH groups can form hydrogen bonds between themselves. For more than one water molecule, there is a competition between water-water and water-phenolic interactions. Ethylene glycol shows the same effects as those of water, but the potential energy surface is further complicated by CH 2 -phenolic interactions, different conformers of ethylene glycol, and two OH groups on each molecule. Thus, the ethylene glycol-phenolic potential is more complicated than the water-phenolic potential. The results of the ab initio calculations are compared to those obtained using a force field. These calibration studies show that the water system is easier to describe than the ethylene glycol system. The calibration studies confirm the reliability of force fields used in our companion molecular dynamics study of a phenolic polymer in water and ethylene solutions.

Atomic Spectral Methods for Ab Initio Molecular Electronic Energy Surfaces: Transitioning From Small-Molecule to Biomolecular-Suitable Approaches.

PubMed

Mills, Jeffrey D; Ben-Nun, Michal; Rollin, Kyle; Bromley, Michael W J; Li, Jiabo; Hinde, Robert J; Winstead, Carl L; Sheehy, Jeffrey A; Boatz, Jerry A; Langhoff, Peter W

2016-08-25

Continuing attention has addressed incorportation of the electronically dynamical attributes of biomolecules in the largely static first-generation molecular-mechanical force fields commonly employed in molecular-dynamics simulations. We describe here a universal quantum-mechanical approach to calculations of the electronic energy surfaces of both small molecules and large aggregates on a common basis which can include such electronic attributes, and which also seems well-suited to adaptation in ab initio molecular-dynamics applications. In contrast to the more familiar orbital-product-based methodologies employed in traditional small-molecule computational quantum chemistry, the present approach is based on an "ex-post-facto" method in which Hamiltonian matrices are evaluated prior to wave function antisymmetrization, implemented here in the support of a Hilbert space of orthonormal products of many-electron atomic spectral eigenstates familiar from the van der Waals theory of long-range interactions. The general theory in its various forms incorporates the early semiempirical atoms- and diatomics-in-molecules approaches of Moffitt, Ellison, Tully, Kuntz, and others in a comprehensive mathematical setting, and generalizes the developments of Eisenschitz, London, Claverie, and others addressing electron permutation symmetry adaptation issues, completing these early attempts to treat van der Waals and chemical forces on a common basis. Exact expressions are obtained for molecular Hamiltonian matrices and for associated energy eigenvalues as sums of separate atomic and interaction-energy terms, similar in this respect to the forms of classical force fields. The latter representation is seen to also provide a long-missing general definition of the energies of individual atoms and of their interactions within molecules and matter free from subjective additional constraints. A computer code suite is described for calculations of the many-electron atomic eigenspectra and the pairwise-atomic Hamiltonian matrices required for practical applications. These matrices can be retained as functions of scalar atomic-pair separations and employed in assembling aggregate Hamiltonian matrices, with Wigner rotation matrices providing analytical representations of their angular degrees of freedom. In this way, ab initio potential energy surfaces are obtained in the complete absence of repeated evaluations and transformations of the one- and two-electron integrals at different molecular geometries required in most ab inito molecular calculations, with large Hamiltonian matrix assembly simplified and explicit diagonalizations avoided employing partitioning and Brillouin-Wigner or Rayleigh-Schrödinger perturbation theory. Illustrative applications of the important components of the formalism, selected aspects of the scaling of the approach, and aspects of "on-the-fly" interfaces with Monte Carlo and molecular-dynamics methods are described in anticipation of subsequent applications to biomolecules and other large aggregates.

Molecular Modeling of Thermodynamic and Transport Properties for CO 2 and Aqueous Brines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Hao; Economou, Ioannis G.; Panagiotopoulos, Athanassios Z.

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models formore » water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2, and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2-rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion–ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Lastly, another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.« less

Molecular Modeling of Thermodynamic and Transport Properties for CO2 and Aqueous Brines.

PubMed

Jiang, Hao; Economou, Ioannis G; Panagiotopoulos, Athanassios Z

2017-04-18

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models for water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2 , and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2 -rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion-ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.

Molecular Modeling of Thermodynamic and Transport Properties for CO 2 and Aqueous Brines

DOE PAGES

Jiang, Hao; Economou, Ioannis G.; Panagiotopoulos, Athanassios Z.

2017-02-24

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models formore » water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2, and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2-rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion–ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Lastly, another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.« less

The diverse and expanding role of mass spectrometry in structural and molecular biology.

PubMed

Lössl, Philip; van de Waterbeemd, Michiel; Heck, Albert Jr

2016-12-15

The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-deuterium exchange-MS, nowadays enable the characterization of biomolecular structures, functions, and interactions. In particular, we focus on the role of mass spectrometry in integrated structural and molecular biology investigations of biological macromolecular complexes and cellular machineries, highlighting work on CRISPR-Cas systems and eukaryotic transcription complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Applications of molecular modeling in coal research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carlson, G.A.; Faulon, J.L.

Over the past several years, molecular modeling has been applied to study various characteristics of coal molecular structures. Powerful workstations coupled with molecular force-field-based software packages have been used to study coal and coal-related molecules. Early work involved determination of the minimum-energy three-dimensional conformations of various published coal structures (Given, Wiser, Solomon and Shinn), and the dominant role of van der Waals and hydrogen bonding forces in defining the energy-minimized structures. These studies have been extended to explore various physical properties of coal structures, including density, microporosity, surface area, and fractal dimension. Other studies have related structural characteristics to cross-linkmore » density and have explored small molecule interactions with coal. Finally, recent studies using a structural elucidation (molecular builder) technique have constructed statistically diverse coal structures based on quantitative and qualitative data on coal and its decomposition products. This technique is also being applied to study coalification processes based on postulated coalification chemistry.« less

John H. Dillon Medal Lecture: Magnetic Field Directed Self-Assembly of Block Copolymers and Surfactant Mesophases

NASA Astrophysics Data System (ADS)

Osuji, Chinedum

2015-03-01

Molecular self-assembly of block copolymers and small molecule surfactants gives rise to a rich phase behavior as a function of temperature, composition, and other variables. We consider the directed self-assembly of such soft mesophases using magnetic fields, principally through the use of in situ x-ray scattering studies. Field alignment is predicated on a sufficiently large product of magnetic anisotropy and grain size to produce magnetostatic interactions which are substantive relative to thermal forces. We examine the role of field strength on the phase behavior and alignment dynamics of a series of soft mesophases, outlining the possibility to readily create highly ordered functional materials over macroscopic length scales. We show that magnetic fields as large as 10 T have little discernable impact on the stability of block copolymer systems considered, with shifts in order-disorder transition temperatures of roughly 5 mK or smaller. Consequently, directed self-assembly in these systems proceeds by nucleation of randomly aligned grains which thereafter rotate into registry with the field. We highlight the tradeoff between decreasing mobility and increasing anisotropic field interaction that dictates alignment kinetics while transiting from a high temperature disordered state to an ordered system at lower temperatures. NSF support through DMR-0847534 is gratefully acknowledged.

Large-scale molecular dynamics simulation of DNA: implementation and validation of the AMBER98 force field in LAMMPS.

PubMed

Grindon, Christina; Harris, Sarah; Evans, Tom; Novik, Keir; Coveney, Peter; Laughton, Charles

2004-07-15

Molecular modelling played a central role in the discovery of the structure of DNA by Watson and Crick. Today, such modelling is done on computers: the more powerful these computers are, the more detailed and extensive can be the study of the dynamics of such biological macromolecules. To fully harness the power of modern massively parallel computers, however, we need to develop and deploy algorithms which can exploit the structure of such hardware. The Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) is a scalable molecular dynamics code including long-range Coulomb interactions, which has been specifically designed to function efficiently on parallel platforms. Here we describe the implementation of the AMBER98 force field in LAMMPS and its validation for molecular dynamics investigations of DNA structure and flexibility against the benchmark of results obtained with the long-established code AMBER6 (Assisted Model Building with Energy Refinement, version 6). Extended molecular dynamics simulations on the hydrated DNA dodecamer d(CTTTTGCAAAAG)(2), which has previously been the subject of extensive dynamical analysis using AMBER6, show that it is possible to obtain excellent agreement in terms of static, dynamic and thermodynamic parameters between AMBER6 and LAMMPS. In comparison with AMBER6, LAMMPS shows greatly improved scalability in massively parallel environments, opening up the possibility of efficient simulations of order-of-magnitude larger systems and/or for order-of-magnitude greater simulation times.