Science.gov

Sample records for dynamic molecular interactions

  1. Interactive molecular dynamics

    NASA Astrophysics Data System (ADS)

    Schroeder, Daniel V.

    2015-03-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in html5 and javascript for running within any modern Web browser, is provided as an online supplement.

  2. Theoretical analysis of dynamic processes for interacting molecular motors

    NASA Astrophysics Data System (ADS)

    Teimouri, Hamid; Kolomeisky, Anatoly B.; Mehrabiani, Kareem

    2015-02-01

    Biological transport is supported by the collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by carrying out an analysis of a new class of totally asymmetric exclusion processes, in which interactions are accounted for in a thermodynamically consistent fashion. This allows us to explicitly connect microscopic features of motor proteins with their collective dynamic properties. A theoretical analysis that combines various mean-field calculations and computer simulations suggests that the dynamic properties of molecular motors strongly depend on the interactions, and that the correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motor transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed.

  3. Studying Interactions by Molecular Dynamics Simulations at High Concentration

    PubMed Central

    Fogolari, Federico; Corazza, Alessandra; Toppo, Stefano; Tosatto, Silvio C. E.; Viglino, Paolo; Ursini, Fulvio; Esposito, Gennaro

    2012-01-01

    Molecular dynamics simulations have been used to study molecular encounters and recognition. In recent works, simulations using high concentration of interacting molecules have been performed. In this paper, we consider the practical problems for setting up the simulation and to analyse the results of the simulation. The simulation of beta 2-microglobulin association and the simulation of the binding of hydrogen peroxide by glutathione peroxidase are provided as examples. PMID:22500085

  4. Electron-phonon interaction within classical molecular dynamics

    NASA Astrophysics Data System (ADS)

    Tamm, A.; Samolyuk, G.; Correa, A. A.; Klintenberg, M.; Aabloo, A.; Caro, A.

    2016-07-01

    We present a model for nonadiabatic classical molecular dynamics simulations that captures with high accuracy the wave-vector q dependence of the phonon lifetimes, in agreement with quantum mechanics calculations. It is based on a local view of the e -ph interaction where individual atom dynamics couples to electrons via a damping term that is obtained as the low-velocity limit of the stopping power of a moving ion in a host. The model is parameter free, as its components are derived from ab initio-type calculations, is readily extended to the case of alloys, and is adequate for large-scale molecular dynamics computer simulations. We also show how this model removes some oversimplifications of the traditional ionic damped dynamics commonly used to describe situations beyond the Born-Oppenheimer approximation.

  5. Electron-phonon interaction within classical molecular dynamics

    DOE PAGESBeta

    Tamm, A.; Samolyuk, G.; Correa, A. A.; Klintenberg, M.; Aabloo, A.; Caro, A.

    2016-07-14

    Here, we present a model for nonadiabatic classical molecular dynamics simulations that captures with high accuracy the wave-vector q dependence of the phonon lifetimes, in agreement with quantum mechanics calculations. It is based on a local view of the e-ph interaction where individual atom dynamics couples to electrons via a damping term that is obtained as the low-velocity limit of the stopping power of a moving ion in a host. The model is parameter free, as its components are derived from ab initio-type calculations, is readily extended to the case of alloys, and is adequate for large-scale molecular dynamics computermore » simulations. We also show how this model removes some oversimplifications of the traditional ionic damped dynamics commonly used to describe situations beyond the Born-Oppenheimer approximation.« less

  6. Molecular dynamics simulation of complex plasmas: interaction of nonlinear waves

    NASA Astrophysics Data System (ADS)

    Durniak, Celine; Samsonov, Dmitry

    2008-11-01

    Complex plasmas consist of micron sized microspheres immersed into ordinary ion-electron plasmas. They exist in solid, liquid, gaseous states and exhibit a range of dynamic phenomena such as waves, solitons, phase transitions, heat transfer. These phenomena can be modelled in complex plasmas at the microscopic or ``molecular'' scale, which is almost impossible in ordinary solids and liquids. We simulate a monolayer complex plasma consisting of 3000 negatively-charged particles (or grains) with the help of molecular dynamics computer simulations. The equations of grain motion are solved using a 5^th order Runge Kutta method taking into account interaction of every grain with each other via a Yukawa potential. The grains are confined more strongly in the vertical direction than in the horizontal. After seeding the grains randomly the code is run until the equilibrium is reached as the grain kinetics energy reduces due to damping force equal to the neutral friction in the experiments and a monolayer crystal lattice is formed. Then we investigate interactions between nonlinear waves in a monolayer strongly coupled complex plasma moving in three dimensions. Different excitations are applied during a short time symmetrically on both sides of the lattice. Structural properties and nonlinear waves characteristics are examined as the pulses propagate across the complex plasma in opposite directions.

  7. Molecular Dynamics of "Fuzzy" Transcriptional Activator-Coactivator Interactions.

    PubMed

    Scholes, Natalie S; Weinzierl, Robert O J

    2016-05-01

    Transcriptional activation domains (ADs) are generally thought to be intrinsically unstructured, but capable of adopting limited secondary structure upon interaction with a coactivator surface. The indeterminate nature of this interface made it hitherto difficult to study structure/function relationships of such contacts. Here we used atomistic accelerated molecular dynamics (aMD) simulations to study the conformational changes of the GCN4 AD and variants thereof, either free in solution, or bound to the GAL11 coactivator surface. We show that the AD-coactivator interactions are highly dynamic while obeying distinct rules. The data provide insights into the constant and variable aspects of orientation of ADs relative to the coactivator, changes in secondary structure and energetic contributions stabilizing the various conformers at different time points. We also demonstrate that a prediction of α-helical propensity correlates directly with the experimentally measured transactivation potential of a large set of mutagenized ADs. The link between α-helical propensity and the stimulatory activity of ADs has fundamental practical and theoretical implications concerning the recruitment of ADs to coactivators. PMID:27175900

  8. Molecular Dynamics of "Fuzzy" Transcriptional Activator-Coactivator Interactions

    PubMed Central

    Scholes, Natalie S.; Weinzierl, Robert O. J.

    2016-01-01

    Transcriptional activation domains (ADs) are generally thought to be intrinsically unstructured, but capable of adopting limited secondary structure upon interaction with a coactivator surface. The indeterminate nature of this interface made it hitherto difficult to study structure/function relationships of such contacts. Here we used atomistic accelerated molecular dynamics (aMD) simulations to study the conformational changes of the GCN4 AD and variants thereof, either free in solution, or bound to the GAL11 coactivator surface. We show that the AD-coactivator interactions are highly dynamic while obeying distinct rules. The data provide insights into the constant and variable aspects of orientation of ADs relative to the coactivator, changes in secondary structure and energetic contributions stabilizing the various conformers at different time points. We also demonstrate that a prediction of α-helical propensity correlates directly with the experimentally measured transactivation potential of a large set of mutagenized ADs. The link between α-helical propensity and the stimulatory activity of ADs has fundamental practical and theoretical implications concerning the recruitment of ADs to coactivators. PMID:27175900

  9. Understanding Miltefosine-Membrane Interactions Using Molecular Dynamics Simulations.

    PubMed

    de Sá, Matheus Malta; Sresht, Vishnu; Rangel-Yagui, Carlota Oliveira; Blankschtein, Daniel

    2015-04-21

    Coarse-grained molecular dynamics simulations are used to calculate the free energies of transfer of miltefosine, an alkylphosphocholine anticancer agent, from water to lipid bilayers to study its mechanism of interaction with biological membranes. We consider bilayers containing lipids with different degrees of unsaturation: dipalmitoylphosphatidylcholine (DPPC, saturated, containing 0%, 10%, and 30% cholesterol), dioleoylphosphatidylcholine (DOPC, diunsaturated), palmitoyloleoylphosphatidylcholine (POPC, monounsaturated), diarachidonoylphosphatidylcholine (DAPC, polyunsaturated), and dilinoleylphosphatidylcholine (DUPC, polyunsaturated). These free energies, calculated using umbrella sampling, were used to compute the partition coefficients (K) of miltefosine between water and the lipid bilayers. The K values for the bilayers relative to that of pure DPPC were found to be 5.3 (DOPC), 7.0 (POPC), 1.0 (DAPC), 2.2 (DUPC), 14.9 (10% cholesterol), and 76.2 (30% cholesterol). Additionally, we calculated the free energy of formation of miltefosine-cholesterol complexes by pulling the surfactant laterally in the DPPC + 30% cholesterol system. The free energy profile that we obtained provides further evidence that miltefosine tends to associate with cholesterol and has a propensity to partition into lipid rafts. We also quantified the kinetics of the transport of miltefosine through the various bilayers by computing permeance values. The highest permeance was observed in DUPC bilayers (2.28 × 10(-2) m/s) and the lowest permeance in the DPPC bilayer with 30% cholesterol (1.10 × 10(-7) m/s). Our simulation results show that miltefosine does indeed interact with lipid rafts, has a higher permeability in polyunsaturated, loosely organized bilayers, and has higher flip-flop rates in specific regions of cellular membranes. PMID:25819781

  10. Evaluating Molecular Interactions in Polycaprolactone-Biomineralized Hydroxyapatite Nanocomposites using Steered Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Sharma, Anurag; Payne, Scott; Katti, Kalpana S.; Katti, Dinesh R.

    2015-04-01

    An experimental and modeling study of a complex nanoclay-based polymeric scaffold system is presented here. A representative molecular model of polymeric nanocomposite scaffold system for bone tissue engineering applications was developed. Polymeric scaffolds were synthesized using organically modified montmorillonite clay (OMMT) with biomineralized hydroxyapatite and polycaprolactone (OMMT-HAP-PCL). The OMMT-HAP-PCL representative model was constructed and validated using transmission electron microscopy, x-ray diffraction and material density results. We observed strong molecular interactions between OMMT, hydroxyapatite (HAP) and polycaprolactone (PCL) in the OMMT-HAP-PCL system. Attractive and repulsive interactions between PCL and different constituents of OMMT and HAP indicate influence of OMMT-HAP on PCL. Polymeric scaffolds were found to have improved nanomechanical properties as compared to pristine PCL due to the introduction of OMMT-HAP. Stress-strain response for the representative OMMT-HAP-PCL model was evaluated using constant force steered molecular dynamics (SMD) simulations. Two distinct stress-strain responses observed in the system indicate a two-phase nanomechanical behavior of OMMT-HAP-PCL obtained at low and high applied stresses. The results obtained from the MD and SMD simulations provide quantitative understanding of molecular interactions between different constituents of OMMT, HAP and PCL and mechanical response in the OMMT-HAP-PCL system.

  11. Molecular dynamics modeling of a nanomaterials-water surface interaction

    NASA Astrophysics Data System (ADS)

    Nejat Pishkenari, Hossein; Keramati, Ramtin; Abdi, Ahmad; Minary-Jolandan, Majid

    2016-04-01

    In this article, we study the formation of nanomeniscus around a nanoneedle using molecular dynamics simulation approach. The results reveal three distinct phases in the time-evolution of meniscus before equilibrium according to the contact angle, meniscus height, and potential energy. In addition, we investigated the correlation between the nanoneedle diameter and nanomeniscus characteristics. The results have applications in various fields such as scanning probe microscopy and rheological measurements.

  12. Ranking of Molecular Biomarker Interaction with Targeted DNA Nucleobases via Full Atomistic Molecular Dynamics.

    PubMed

    Zhang, Wenjun; Wang, Ming L; Cranford, Steven W

    2016-01-01

    DNA-based sensors can detect disease biomarkers, including acetone and ethanol for diabetes and H2S for cardiovascular diseases. Before experimenting on thousands of potential DNA segments, we conduct full atomistic steered molecular dynamics (SMD) simulations to screen the interactions between different DNA sequences with targeted molecules to rank the nucleobase sensing performance. We study and rank the strength of interaction between four single DNA nucleotides (Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)) on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with acetone, ethanol, H2S and HCl. By sampling forward and reverse interaction paths, we compute the free-energy profiles of eight systems for the four targeted molecules. We find that dsDNA react differently than ssDNA to the targeted molecules, requiring more energy to move the molecule close to DNA as indicated by the potential of mean force (PMF). Comparing the PMF values of different systems, we obtain a relative ranking of DNA base for the detection of each molecule. Via the same procedure, we could generate a library of DNA sequences for the detection of a wide range of chemicals. A DNA sensor array built with selected sequences differentiating many disease biomarkers can be used in disease diagnosis and monitoring. PMID:26750747

  13. Ranking of Molecular Biomarker Interaction with Targeted DNA Nucleobases via Full Atomistic Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Zhang, Wenjun; Wang, Ming L.; Cranford, Steven W.

    2016-01-01

    DNA-based sensors can detect disease biomarkers, including acetone and ethanol for diabetes and H2S for cardiovascular diseases. Before experimenting on thousands of potential DNA segments, we conduct full atomistic steered molecular dynamics (SMD) simulations to screen the interactions between different DNA sequences with targeted molecules to rank the nucleobase sensing performance. We study and rank the strength of interaction between four single DNA nucleotides (Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)) on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with acetone, ethanol, H2S and HCl. By sampling forward and reverse interaction paths, we compute the free-energy profiles of eight systems for the four targeted molecules. We find that dsDNA react differently than ssDNA to the targeted molecules, requiring more energy to move the molecule close to DNA as indicated by the potential of mean force (PMF). Comparing the PMF values of different systems, we obtain a relative ranking of DNA base for the detection of each molecule. Via the same procedure, we could generate a library of DNA sequences for the detection of a wide range of chemicals. A DNA sensor array built with selected sequences differentiating many disease biomarkers can be used in disease diagnosis and monitoring.

  14. Ranking of Molecular Biomarker Interaction with Targeted DNA Nucleobases via Full Atomistic Molecular Dynamics

    PubMed Central

    Zhang, Wenjun; Wang, Ming L.; Cranford, Steven W.

    2016-01-01

    DNA-based sensors can detect disease biomarkers, including acetone and ethanol for diabetes and H2S for cardiovascular diseases. Before experimenting on thousands of potential DNA segments, we conduct full atomistic steered molecular dynamics (SMD) simulations to screen the interactions between different DNA sequences with targeted molecules to rank the nucleobase sensing performance. We study and rank the strength of interaction between four single DNA nucleotides (Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)) on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with acetone, ethanol, H2S and HCl. By sampling forward and reverse interaction paths, we compute the free-energy profiles of eight systems for the four targeted molecules. We find that dsDNA react differently than ssDNA to the targeted molecules, requiring more energy to move the molecule close to DNA as indicated by the potential of mean force (PMF). Comparing the PMF values of different systems, we obtain a relative ranking of DNA base for the detection of each molecule. Via the same procedure, we could generate a library of DNA sequences for the detection of a wide range of chemicals. A DNA sensor array built with selected sequences differentiating many disease biomarkers can be used in disease diagnosis and monitoring. PMID:26750747

  15. Molecular dynamics

    SciTech Connect

    Ladd, A.J.C.

    1988-08-01

    The basic methodology of equilibrium molecular dynamics is described. Examples from the literature are used to illustrate how molecular dynamics has been used to resolve theoretical controversies, provide data to test theories, and occasionally to discover new phenomena. The emphasis is on the application of molecular dynamics to an understanding of the microscopic physics underlying the transport properties of simple fluids. 98 refs., 4 figs.

  16. Transmembrane helix structure, dynamics, and interactions: multi-nanosecond molecular dynamics simulations.

    PubMed Central

    Shen, L; Bassolino, D; Stouch, T

    1997-01-01

    To probe the fundamentals of membrane/protein interactions, all-atom multi-nanosecond molecular dynamics simulations were conducted on a single transmembrane poly(32)alanine helix in a fully solvated dimyristoyphosphatidylcholine (DMPC) bilayer. The central 12 residues, which interact only with the lipid hydrocarbon chains, maintained a very stable helical structure. Helical regions extended beyond these central 12 residues, but interactions with the lipid fatty-acyl ester linkages, the lipid headgroups, and water molecules made the helix less stable in this region. The C and N termini, exposed largely to water, existed as random coils. As a whole, the helix tilted substantially, from perpendicular to the bilayer plane (0 degree) to a 30 degrees tilt. The helix experienced a bend at its middle, and the two halves of the helix at times assumed substantially different tilts. Frequent hydrogen bonding, of up to 0.7 ns in duration, occurred between peptide and lipid molecules. This resulted in correlated translational diffusion between the helix and a few lipid molecules. Because of the large variation in lipid conformation, the lipid environment of the peptide was not well defined in terms of "annular" lipids and on average consisted of 18 lipid molecules. When compared with a "neat" bilayer without peptide, no significant difference was seen in the bilayer thickness, lipid conformations or diffusion, or headgroup orientation. However, the lipid hydrocarbon chain order parameters showed a significant decrease in order, especially in those methylene groups closest to the headgroup. Images FIGURE 1 FIGURE 14 PMID:9199766

  17. Molecular Dynamic Simulations of Interaction of an AFM Probe with the Surface of an SCN Sample

    NASA Technical Reports Server (NTRS)

    Bune, Adris; Kaukler, William; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    Molecular dynamic (MD) simulations is conducted in order to estimate forces of probe-substrate interaction in the Atomic Force Microscope (AFM). First a review of available molecular dynamic techniques is given. Implementation of MD simulation is based on an object-oriented code developed at the University of Delft. Modeling of the sample material - succinonitrile (SCN) - is based on the Lennard-Jones potentials. For the polystyrene probe an atomic interaction potential is used. Due to object-oriented structure of the code modification of an atomic interaction potential is straight forward. Calculation of melting temperature is used for validation of the code and of the interaction potentials. Various fitting parameters of the probe-substrate interaction potentials are considered, as potentials fitted to certain properties and temperature ranges may not be reliable for the others. This research provides theoretical foundation for an interpretation of actual measurements of an interaction forces using AFM.

  18. DyNet: visualization and analysis of dynamic molecular interaction networks

    PubMed Central

    Goenawan, Ivan H.; Lynn, David J.

    2016-01-01

    Summary: The ability to experimentally determine molecular interactions on an almost proteome-wide scale under different conditions is enabling researchers to move from static to dynamic network analysis, uncovering new insights into how interaction networks are physically rewired in response to different stimuli and in disease. Dynamic interaction data presents a special challenge in network biology. Here, we present DyNet, a Cytoscape application that provides a range of functionalities for the visualization, real-time synchronization and analysis of large multi-state dynamic molecular interaction networks enabling users to quickly identify and analyze the most ‘rewired’ nodes across many network states. Availability and Implementation: DyNet is available at the Cytoscape (3.2+) App Store (http://apps.cytoscape.org/apps/dynet). Contact: david.lynn@sahmri.com. Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:27153624

  19. Correlations and symmetry of interactions influence collective dynamics of molecular motors

    NASA Astrophysics Data System (ADS)

    Celis-Garza, Daniel; Teimouri, Hamid; Kolomeisky, Anatoly B.

    2015-04-01

    Enzymatic molecules that actively support many cellular processes, including transport, cell division and cell motility, are known as motor proteins or molecular motors. Experimental studies indicate that they interact with each other and they frequently work together in large groups. To understand the mechanisms of collective behavior of motor proteins we study the effect of interactions in the transport of molecular motors along linear filaments. It is done by analyzing a recently introduced class of totally asymmetric exclusion processes that takes into account the intermolecular interactions via thermodynamically consistent approach. We develop a new theoretical method that allows us to compute analytically all dynamic properties of the system. Our analysis shows that correlations play important role in dynamics of interacting molecular motors. Surprisingly, we find that the correlations for repulsive interactions are weaker and more short-range than the correlations for the attractive interactions. In addition, it is shown that symmetry of interactions affect dynamic properties of molecular motors. The implications of these findings for motor proteins transport are discussed. Our theoretical predictions are tested by extensive Monte Carlo computer simulations.

  20. Lipid interaction sites on channels, transporters and receptors: Recent insights from molecular dynamics simulations.

    PubMed

    Hedger, George; Sansom, Mark S P

    2016-10-01

    Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterization of these sites are of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. PMID:26946244

  1. A molecular dynamics study on slow ion interactions with the polycyclic aromatic hydrocarbon molecule anthracene

    SciTech Connect

    Postma, J.; Hoekstra, R.; Schlathölter, T.; Tielens, A. G. G. M.

    2014-03-01

    Atomic collisions with polycyclic aromatic hydrocarbon (PAH) molecules are astrophysically particularly relevant for collision energies of less than 1 keV. In this regime, the interaction dynamics are dominated by elastic interactions. We have employed a molecular dynamics simulation based on analytical interaction potentials to model the interaction of low energy hydrogen and helium projectiles with isolated anthracene (C{sub 14}H{sub 10}) molecules. This approach allows for a very detailed investigation of the elastic interaction dynamics on an event by event basis. From the simulation data the threshold projectile kinetic energies above which direct C atom knock out sets in were determined. Anthracene differential energy transfer cross sections and total (dissociation) cross sections were computed for a wide range of projectile kinetic energies. The obtained results are interpreted in the context of PAH destruction in astrophysical environments.

  2. Molecular Dynamics Study on the Biophysical Interactions of Seven Green Tea Catechins with Cell Membranes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Molecular dynamics simulations were performed to study the interactions of bioactive catechins (flavonoids) commonly found in green tea with lipid bilayers, as model for cell membranes. Previously, a number of experimental studies rationalized catechin’s anticarcinogenic, antibacterial, and other be...

  3. Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations.

    PubMed

    Hardy, David J; Wolff, Matthew A; Xia, Jianlin; Schulten, Klaus; Skeel, Robert D

    2016-03-21

    The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B-splines to increase the accuracy of the multilevel summation method (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle-mesh Ewald method falls short. PMID:27004867

  4. Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Hardy, David J.; Wolff, Matthew A.; Xia, Jianlin; Schulten, Klaus; Skeel, Robert D.

    2016-03-01

    The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B-splines to increase the accuracy of the multilevel summation method (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle-mesh Ewald method falls short.

  5. Three-dimensional interactive Molecular Dynamics program for the study of defect dynamics in crystals

    NASA Astrophysics Data System (ADS)

    Patriarca, M.; Kuronen, A.; Robles, M.; Kaski, K.

    2007-01-01

    The study of crystal defects and the complex processes underlying their formation and time evolution has motivated the development of the program ALINE for interactive molecular dynamics experiments. This program couples a molecular dynamics code to a Graphical User Interface and runs on a UNIX-X11 Window System platform with the MOTIF library, which is contained in many standard Linux releases. ALINE is written in C, thus giving the user the possibility to modify the source code, and, at the same time, provides an effective and user-friendly framework for numerical experiments, in which the main parameters can be interactively varied and the system visualized in various ways. We illustrate the main features of the program through some examples of detection and dynamical tracking of point-defects, linear defects, and planar defects, such as stacking faults in lattice-mismatched heterostructures. Program summaryTitle of program:ALINE Catalogue identifier:ADYJ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYJ_v1_0 Program obtainable from: CPC Program Library, Queen University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: Computers:DEC ALPHA 300, Intel i386 compatible computers, G4 Apple Computers Installations:Laboratory of Computational Engineering, Helsinki University of Technology, Helsinki, Finland Operating systems under which the program has been tested:True64 UNIX, Linux-i386, Mac OS X 10.3 and 10.4 Programming language used:Standard C and MOTIF libraries Memory required to execute with typical data:6 Mbytes but may be larger depending on the system size No. of lines in distributed program, including test data, etc.:16 901 No. of bytes in distributed program, including test data, etc.:449 559 Distribution format:tar.gz Nature of physical problem:Some phenomena involving defects take place inside three-dimensional crystals at times which can be hardly predicted. For this reason they are

  6. Multiscale modeling of dislocation-precipitate interactions in Fe: From molecular dynamics to discrete dislocations

    NASA Astrophysics Data System (ADS)

    Lehtinen, Arttu; Granberg, Fredric; Laurson, Lasse; Nordlund, Kai; Alava, Mikko J.

    2016-01-01

    The stress-driven motion of dislocations in crystalline solids, and thus the ensuing plastic deformation process, is greatly influenced by the presence or absence of various pointlike defects such as precipitates or solute atoms. These defects act as obstacles for dislocation motion and hence affect the mechanical properties of the material. Here we combine molecular dynamics studies with three-dimensional discrete dislocation dynamics simulations in order to model the interaction between different kinds of precipitates and a 1/2 <111 > {110 } edge dislocation in BCC iron. We have implemented immobile spherical precipitates into the ParaDis discrete dislocation dynamics code, with the dislocations interacting with the precipitates via a Gaussian potential, generating a normal force acting on the dislocation segments. The parameters used in the discrete dislocation dynamics simulations for the precipitate potential, the dislocation mobility, shear modulus, and dislocation core energy are obtained from molecular dynamics simulations. We compare the critical stresses needed to unpin the dislocation from the precipitate in molecular dynamics and discrete dislocation dynamics simulations in order to fit the two methods together and discuss the variety of the relevant pinning and depinning mechanisms.

  7. Multiscale modeling of dislocation-precipitate interactions in Fe: From molecular dynamics to discrete dislocations.

    PubMed

    Lehtinen, Arttu; Granberg, Fredric; Laurson, Lasse; Nordlund, Kai; Alava, Mikko J

    2016-01-01

    The stress-driven motion of dislocations in crystalline solids, and thus the ensuing plastic deformation process, is greatly influenced by the presence or absence of various pointlike defects such as precipitates or solute atoms. These defects act as obstacles for dislocation motion and hence affect the mechanical properties of the material. Here we combine molecular dynamics studies with three-dimensional discrete dislocation dynamics simulations in order to model the interaction between different kinds of precipitates and a 1/2〈111〉{110} edge dislocation in BCC iron. We have implemented immobile spherical precipitates into the ParaDis discrete dislocation dynamics code, with the dislocations interacting with the precipitates via a Gaussian potential, generating a normal force acting on the dislocation segments. The parameters used in the discrete dislocation dynamics simulations for the precipitate potential, the dislocation mobility, shear modulus, and dislocation core energy are obtained from molecular dynamics simulations. We compare the critical stresses needed to unpin the dislocation from the precipitate in molecular dynamics and discrete dislocation dynamics simulations in order to fit the two methods together and discuss the variety of the relevant pinning and depinning mechanisms. PMID:26871192

  8. Parallel implementation of three-dimensional molecular dynamic simulation for laser-cluster interaction

    SciTech Connect

    Holkundkar, Amol R.

    2013-11-15

    The objective of this article is to report the parallel implementation of the 3D molecular dynamic simulation code for laser-cluster interactions. The benchmarking of the code has been done by comparing the simulation results with some of the experiments reported in the literature. Scaling laws for the computational time is established by varying the number of processor cores and number of macroparticles used. The capabilities of the code are highlighted by implementing various diagnostic tools. To study the dynamics of the laser-cluster interactions, the executable version of the code is available from the author.

  9. Molecular mechanics and dynamics studies on the interaction of gallic acid with collagen-like peptides

    NASA Astrophysics Data System (ADS)

    Madhan, B.; Thanikaivelan, P.; Subramanian, V.; Raghava Rao, J.; Unni Nair, Balachandran; Ramasami, T.

    2001-10-01

    Molecular modelling approaches have been used to understand the interaction of collagen-like peptides with gallic acid, which mimic vegetable tanning processes involved in protein stabilization. Several interaction sites have been identified and the binding energies of the complexes have been calculated. The calculated binding energies for various geometries are in the range 6-13 kcal/mol. It is found that some complexes exhibit hydrogen bonding, and electrostatic interaction plays a dominant role in the stabilization of the peptide by gallic acid. The π-OH type of interaction is also observed in the peptide stabilization. Molecular dynamics (MD) simulation for 600 ps revealed the possibility of hydrogen bonding between the collagen-like peptide and gallic acid.

  10. Computational analysis of C-reactive protein for assessment of molecular dynamics and interaction properties.

    PubMed

    Chakraborty, Chiranjib; Agrawal, Alok

    2013-11-01

    Serum C-reactive protein (CRP) is used as a marker of inflammation in several diseases including autoimmune disease and cardiovascular disease. CRP, a member of the pentraxin family, is comprised of five identical subunits. CRP has diverse ligand-binding properties which depend upon different structural states of CRP. However, little is known about the molecular dynamics and interaction properties of CRP. In this study, we used SAPS, SCRATCH protein predictor, PDBsum, ConSurf, ProtScale, Drawhca, ASAView, SCide and SRide server and performed comprehensive analyses of molecular dynamics, protein-protein and residue-residue interactions of CRP. We used 1GNH.pdb file for the crystal structure of human CRP which generated two pentamers (ABCDE and FGHIJ). The number of residues involved in residue-residue interactions between A-B, B-C, C-D, D-E, F-G, G-H, H-I, I-J, A-E and F-J subunits were 12, 11, 10, 11, 12, 11, 10, 11, 10 and 10, respectively. Fifteen antiparallel β sheets were involved in β-sheet topology, and five β hairpins were involved in forming the secondary structure. Analysis of hydrophobic segment distribution revealed deviations in surface hydrophobicity at different cavities present in CRP. Approximately 33 % of all residues were involved in the stabilization centers. We show that the bioinformatics tools can provide a rapid method to predict molecular dynamics and interaction properties of CRP. Our prediction of molecular dynamics and interaction properties of CRP combined with the modeling data based on the known 3D structure of CRP is helpful in designing stable forms of CRP mutants for structure-function studies of CRP and may facilitate in silico drug design for therapeutic targeting of CRP. PMID:23494263

  11. Computational Analysis of C-Reactive Protein for Assessment of Molecular Dynamics and Interaction Properties

    PubMed Central

    Agrawal, Alok

    2013-01-01

    Serum C-reactive protein (CRP) is used as a marker of inflammation in several diseases including autoimmune disease and cardiovascular disease. CRP, a member of the pentraxin family, is comprised of five identical subunits. CRP has diverse ligand-binding properties which depend upon different structural states of CRP. However, little is known about the molecular dynamics and interaction properties of CRP. In this study, we used SAPS, SCRATCH protein predictor, PDBsum, ConSurf, ProtScale, Drawhca, ASAView, SCide and SRide server and performed comprehensive analyses of molecular dynamics, protein–protein and residue–residue interactions of CRP. We used 1GNH.pdb file for the crystal structure of human CRP which generated two pentamers (ABCDE and FGHIJ). The number of residues involved in residue–residue interactions between A–B, B–C, C–D, D–E, F–G, G–H, H–I, I–J, A–E and F–J subunits were 12, 11, 10, 11, 12, 11, 10, 11, 10 and 10, respectively. Fifteen antiparallel β sheets were involved in β-sheet topology, and five β hairpins were involved in forming the secondary structure. Analysis of hydrophobic segment distribution revealed deviations in surface hydrophobicity at different cavities present in CRP. Approximately 33 % of all residues were involved in the stabilization centers. We show that the bioinformatics tools can provide a rapid method to predict molecular dynamics and interaction properties of CRP. Our prediction of molecular dynamics and interaction properties of CRP combined with the modeling data based on the known 3D structure of CRP is helpful in designing stable forms of CRP mutants for structure–function studies of CRP and may facilitate in silico drug design for therapeutic targeting of CRP. PMID:23494263

  12. Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy

    PubMed Central

    Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

    2015-01-01

    The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA. PMID:26140374

  13. Interactions between ether phospholipids and cholesterol as determined by scattering and molecular dynamics simulations.

    PubMed

    Pan, Jianjun; Cheng, Xiaolin; Heberle, Frederick A; Mostofian, Barmak; Kučerka, Norbert; Drazba, Paul; Katsaras, John

    2012-12-27

    Cholesterol and ether lipids are ubiquitous in mammalian cell membranes, and their interactions are crucial in ether lipid mediated cholesterol trafficking. We report on cholesterol's molecular interactions with ether lipids as determined using a combination of small-angle neutron and X-ray scattering, and all-atom molecular dynamics (MD) simulations. A scattering density profile model for an ether lipid bilayer was developed using MD simulations, which was then used to simultaneously fit the different experimental scattering data. From analysis of the data the various bilayer structural parameters were obtained. Surface area constrained MD simulations were also performed to reproduce the experimental data. This iterative analysis approach resulted in good agreement between the experimental and simulated form factors. The molecular interactions taking place between cholesterol and ether lipids were then determined from the validated MD simulations. We found that in ether membranes cholesterol primarily hydrogen bonds with the lipid headgroup phosphate oxygen, while in their ester membrane counterparts cholesterol hydrogen bonds with the backbone ester carbonyls. This different mode of interaction between ether lipids and cholesterol induces cholesterol to reside closer to the bilayer surface, dehydrating the headgroup's phosphate moiety. Moreover, the three-dimensional lipid chain spatial density distribution around cholesterol indicates anisotropic chain packing, causing cholesterol to tilt. These insights lend a better understanding of ether lipid-mediated cholesterol trafficking and the roles that the different lipid species have in determining the structural and dynamical properties of membrane associated biomolecules. PMID:23199292

  14. Interactions between Ether Phospholipids and Cholesterol as Determined by Scattering and Molecular Dynamics Simulations

    SciTech Connect

    Pan, Jianjun; Cheng, Xiaolin; Heberle, Frederick A; Mostofian, Barmak; Kucerka, Norbert; Drazba, Paul; Katsaras, John

    2012-01-01

    Cholesterol and ether lipids are ubiquitous in mammalian cell membranes, and their interactions are crucial in ether lipid mediated cholesterol trafficking. We report on cholesterol s molecular interactions with ether lipids as determined using a combination of small-angle neutron and Xray scattering, and all-atom molecular dynamics (MD) simulations. A scattering density profile model for an ether lipid bilayer was developed using MD simulations, which was then used to simultaneously fit the different experimental scattering data. From analysis of the data the various bilayer structural parameters were obtained. Surface area constrained MD simulations were also performed to reproduce the experimental data. This iterative analysis approach resulted in good agreement between the experimental and simulated form factors. The molecular interactions taking place between cholesterol and ether lipids were then determined from the validated MD simulations. We found that in ether membranes cholesterol primarily hydrogen bonds with the lipid headgroup phosphate oxygen, while in their ester membrane counterparts cholesterol hydrogen bonds with the backbone ester carbonyls. This different mode of interaction between ether lipids and cholesterol induces cholesterol to reside closer to the bilayer surface, dehydrating the headgroup s phosphate moiety. Moreover, the three-dimensional lipid chain spatial density distribution around cholesterol indicates anisotropic chain packing, causing cholesterol to tilt. These insights lend a better understanding of ether lipid-mediated cholesterol trafficking and the roles that the different lipid species have in determining the structural and dynamical properties of membrane associated biomolecules.

  15. Molecular dynamics simulations of GPCR-cholesterol interaction: An emerging paradigm.

    PubMed

    Sengupta, Durba; Chattopadhyay, Amitabha

    2015-09-01

    G protein-coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across cell membranes and represent major targets in the development of novel drug candidates. Membrane cholesterol plays an important role in GPCR structure and function. Molecular dynamics simulations have been successful in exploring the effect of cholesterol on the receptor and a general consensus molecular view is emerging. We review here recent molecular dynamics studies at multiple resolutions highlighting the main features of cholesterol-GPCR interaction. Several cholesterol interaction sites have been identified on the receptor that are reminiscent of nonannular sites. These cholesterol hot-spots are highly dynamic and have a microsecond time scale of exchange with the bulk lipids. A few consensus sites (such as the CRAC site) have been identified that correspond to higher cholesterol interaction. Interestingly, high plasticity is observed in the modes of cholesterol interaction and several sites have been suggested to have high cholesterol occupancy. We therefore believe that these cholesterol hot-spots are indicative of 'high occupancy sites' rather than 'binding sites'. The results suggest that the energy landscape of cholesterol association with GPCRs corresponds to a series of shallow minima interconnected by low barriers. These specific interactions, along with general membrane effects, have been observed to modulate GPCR organization. Membrane cholesterol effects on receptor structure and organization, that in turn influences receptor cross-talk and drug efficacy, represent a new frontier in GPCR research. This article is part of a Special Issue entitled: Lipid-protein interactions. Guest Editors: Amitabha Chattopadhyay and Jean-Marie Ruysschaert. PMID:25817549

  16. NMR and molecular dynamics studies of the interaction of melatonin with calmodulin

    PubMed Central

    Turjanski, Adrián G.; Estrin, Darío A.; Rosenstein, Ruth E.; McCormick, John E.; Martin, Stephen R.; Pastore, Annalisa; Biekofsky, Rodolfo R.; Martorana, Vincenzo

    2004-01-01

    Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca2+ concentration via activation of its G-protein–coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present work studies the direct interaction of melatonin with intact calcium-saturated CaM both experimentally, by fluorescence and nuclear magnetic resonance spectroscopies, and theoretically, by molecular dynamics simulations. The analysis of the experimental data shows that the interaction is calcium-dependent. The affinity, as obtained from monitoring 15N and 1H chemical shift changes for a melatonin titration, is weak (in the millimolar range) and comparable for the N- and C-terminal domains. Partial replacement of diamagnetic Ca2+ by paramagnetic Tb3+ allowed the measurement of interdomain NMR pseudocontact shifts and residual dipolar couplings, indicating that each domain movement in the complex is not correlated with the other one. Molecular dynamics simulations allow us to follow the dynamics of melatonin in the binding pocket of CaM. Overall, this study provides an example of how a combination of experimental and theoretical approaches can shed light on a weakly interacting system of biological and pharmacological significance. PMID:15498938

  17. NMR and molecular dynamics studies of the interaction of melatonin with calmodulin.

    PubMed

    Turjanski, Adrián G; Estrin, Darío A; Rosenstein, Ruth E; McCormick, John E; Martin, Stephen R; Pastore, Annalisa; Biekofsky, Rodolfo R; Martorana, Vincenzo

    2004-11-01

    Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca(2+) concentration via activation of its G-protein-coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present work studies the direct interaction of melatonin with intact calcium-saturated CaM both experimentally, by fluorescence and nuclear magnetic resonance spectroscopies, and theoretically, by molecular dynamics simulations. The analysis of the experimental data shows that the interaction is calcium-dependent. The affinity, as obtained from monitoring (15)N and (1)H chemical shift changes for a melatonin titration, is weak (in the millimolar range) and comparable for the N- and C-terminal domains. Partial replacement of diamagnetic Ca(2+) by paramagnetic Tb(3+) allowed the measurement of interdomain NMR pseudocontact shifts and residual dipolar couplings, indicating that each domain movement in the complex is not correlated with the other one. Molecular dynamics simulations allow us to follow the dynamics of melatonin in the binding pocket of CaM. Overall, this study provides an example of how a combination of experimental and theoretical approaches can shed light on a weakly interacting system of biological and pharmacological significance. PMID:15498938

  18. PLUMED-GUI: An environment for the interactive development of molecular dynamics analysis and biasing scripts

    NASA Astrophysics Data System (ADS)

    Giorgino, Toni

    2014-03-01

    PLUMED-GUI is an interactive environment to develop and test complex PLUMED scripts within the Visual Molecular Dynamics (VMD) environment. Computational biophysicists can take advantage of both PLUMED’s rich syntax to define collective variables (CVs) and VMD’s chemically-aware atom selection language, while working within a natural point-and-click interface. Pre-defined templates and syntax mnemonics facilitate the definition of well-known reaction coordinates. Complex CVs, e.g. involving reference snapshots used for RMSD or native contacts calculations, can be built through dialogs that provide a synoptic view of the available options. Scripts can be either exported for use in simulation programs, or evaluated on the currently loaded molecular trajectories. Script development takes place without leaving VMD, thus enabling an incremental try-see-modify development model for molecular metrics.

  19. Multiscale Molecular Dynamics Simulations of Beta-Amyloid Interactions with Neurons

    NASA Astrophysics Data System (ADS)

    Qiu, Liming; Vaughn, Mark; Cheng, Kelvin

    2012-10-01

    Early events of human beta-amyloid protein interactions with cholesterol-containing membranes are critical to understanding the pathogenesis of Alzheimer's disease (AD) and to exploring new therapeutic interventions of AD. Atomistic molecular dynamics (AMD) simulations have been extensively used to study the protein-lipid interaction at high atomic resolutions. However, traditional MD simulations are not efficient in sampling the phase space of complex lipid/protein systems with rugged free energy landscapes. Meanwhile, coarse-grained MD (CGD) simulations are efficient in the phase space sampling but suffered from low spatial resolutions and from the fact that the energy landscapes are not identical to those of the AMD. Here, a multiscale approach was employed to simulate the protein-lipid interactions of beta-amyloid upon its release from proteolysis residing in the neuronal membranes. We utilized a forward (AMD to CGD) and reverse (CGD-AMD) strategy to explore new transmembrane and surface protein configuration and evaluate the stabilization mechanisms by measuring the residue-specific protein-lipid or protein conformations. The detailed molecular interactions revealed in this multiscale MD approach will provide new insights into understanding the early molecular events leading to the pathogenesis of AD.

  20. Interaction of Tenebrio Molitor Antifreeze Protein with Ice Crystal: Insights from Molecular Dynamics Simulations.

    PubMed

    Ramya, L; Ramakrishnan, Vigneshwar

    2016-07-01

    Antifreeze proteins (AFP) observed in cold-adapting organisms bind to ice crystals and prevent further ice growth. However, the molecular mechanism of AFP-ice binding and AFP-inhibited ice growth remains unclear. Here we report the interaction of the insect antifreeze protein (Tenebrio molitor, TmAFP) with ice crystal by molecular dynamics simulation studies. Two sets of simulations were carried out at 263 K by placing the protein near the primary prism plane (PP) and basal plane (BL) of the ice crystal. To delineate the effect of temperatures, both the PP and BL simulations were carried out at 253 K as well. The analyses revealed that the protein interacts strongly with the ice crystal in BL simulation than in PP simulation both at 263 K and 253 K. Further, it was observed that the interactions are primarily mediated through the interface waters. We also observed that as the temperature decreases, the interaction between the protein and the ice increases which can be attributed to the decreased flexibility and the increased structuring of the protein at low temperature. In essence, our study has shed light on the interaction mechanism between the TmAFP antifreeze protein and the ice crystal. PMID:27492241

  1. Molecular dynamics simulation for ligand-receptor studies. Carbohydrates interactions in aqueous solutions.

    PubMed

    Grigera, J Raul

    2002-01-01

    The review deals with the problem of the study of ligand-receptor interactions and the use of Molecular Dynamics (MD) simulation to approach such a problem. After a short review of the fundamentals of MD we describe the medium in which all biology takes place, water. Emphasis is put on the water models appropriate for simulation of macromolecular systems explicitly including the water molecules. We consider the quality of the water model both in terms of simplicity and performance to describe the liquid water properties. Heavy water, although not a biologically viable medium, is considered since many experiments make use of it as a solvent. Sweetness of carbohydrates is considered as an example of the procedure suitable to characterize active sites on the ligands. Consideration is given to the computation of the binding constants through molecular dynamics. The computation of the Free Energy is described and illustrated. The potentiality of MD for studies of ligand-receptor interactions is limited by the computer resources, for even with large computing facilities the need of relatively long simulation times severely restricts the study of large systems. A method is described in which several shells are treated at different levels of approximation, form mechanical response and mean electrical field to quantum mechanics, through stochastic dynamics and atomic classical MD. The review closes with a brief account of the perspectives of the method. PMID:12052202

  2. Generalized image charge solvation model for electrostatic interactions in molecular dynamics simulations of aqueous solutions

    NASA Astrophysics Data System (ADS)

    Deng, Shaozhong; Xue, Changfeng; Baumketner, Andriy; Jacobs, Donald; Cai, Wei

    2013-07-01

    This paper extends the image charge solvation model (ICSM) [Y. Lin, A. Baumketner, S. Deng, Z. Xu, D. Jacobs, W. Cai, An image-based reaction field method for electrostatic interactions in molecular dynamics simulations of aqueous solutions, J. Chem. Phys. 131 (2009) 154103], a hybrid explicit/implicit method to treat electrostatic interactions in computer simulations of biomolecules formulated for spherical cavities, to prolate spheroidal and triaxial ellipsoidal cavities, designed to better accommodate non-spherical solutes in molecular dynamics (MD) simulations. In addition to the utilization of a general truncated octahedron as the MD simulation box, central to the proposed extension is an image approximation method to compute the reaction field for a point charge placed inside such a non-spherical cavity by using a single image charge located outside the cavity. The resulting generalized image charge solvation model (GICSM) is tested in simulations of liquid water, and the results are analyzed in comparison with those obtained from the ICSM simulations as a reference. We find that, for improved computational efficiency due to smaller simulation cells and consequently a less number of explicit solvent molecules, the generalized model can still faithfully reproduce known static and dynamic properties of liquid water at least for systems considered in the present paper, indicating its great potential to become an accurate but more efficient alternative to the ICSM when bio-macromolecules of irregular shapes are to be simulated.

  3. Molecular dynamic and docking interaction study of Heterodera glycines serine proteinase with Vigna mungo proteinase inhibitor.

    PubMed

    Prasad, C V S Siva; Gupta, Saurabh; Gaponenko, Alex; Tiwari, Murlidhar

    2013-08-01

    Many plants do produce various defense proteins like proteinase inhibitors (PIs) to protect them against various pests. PIs function as pseudosubstrates of digestive proteinase, which inhibits proteolysis in pests and leads to amino acid deficiency-based mortality. This work reports the structural interaction studies of serine proteinase of Heterodera glycines (SPHG) with Vigna mungo proteinase inhibitor (VMPI). 3D protein structure modeling, validation of SPHG and VMPI, and their putative protein-protein binding sites were predicted. Protein-protein docking followed by molecular dynamic simulation was performed to find the reliable confirmation of SPHG-VMPI complex. Trajectory analysis of each successive conformation concludes better interaction of first loop in comparison with second loop. Lysine residues of first loop were actively participating in complex formation. Overall, this study discloses the structural aspects and interaction mechanisms of VMPI with SPHG, and it would be helpful in the development of pest-resistant genetically modified crops. PMID:23813339

  4. How does the molecular linker in dynamic force spectroscopy affect probing molecular interactions at the single-molecule level?

    NASA Astrophysics Data System (ADS)

    Taninaka, Atsushi; Aizawa, Kota; Hanyu, Tatsuya; Hirano, Yuuichi; Takeuchi, Osamu; Shigekawa, Hidemi

    2016-08-01

    Dynamic force spectroscopy (DFS) based on atomic force microscopy, which enables us to obtain information on the interaction potential between molecules such as antigen-antibody complexes at the single-molecule level, is a key technique for advancing molecular science and technology. However, to ensure the reliability of DFS measurement, its basic mechanism must be well understood. We examined the effect of the molecular linker used to fix the target molecule to the atomic force microscope cantilever, i.e., the force direction during measurement, for the first time, which has not been discussed until now despite its importance. The effect on the lifetime and barrier position, which can be obtained by DFS, was found to be ˜10 and ˜50%, respectively, confirming the high potential of DFS.

  5. How does the molecular linker in dynamic force spectroscopy affect probing molecular interactions at the single-molecule level?

    NASA Astrophysics Data System (ADS)

    Taninaka, Atsushi; Aizawa, Kota; Hanyu, Tatsuya; Hirano, Yuuichi; Takeuchi, Osamu; Shigekawa, Hidemi

    2016-08-01

    Dynamic force spectroscopy (DFS) based on atomic force microscopy, which enables us to obtain information on the interaction potential between molecules such as antigen–antibody complexes at the single-molecule level, is a key technique for advancing molecular science and technology. However, to ensure the reliability of DFS measurement, its basic mechanism must be well understood. We examined the effect of the molecular linker used to fix the target molecule to the atomic force microscope cantilever, i.e., the force direction during measurement, for the first time, which has not been discussed until now despite its importance. The effect on the lifetime and barrier position, which can be obtained by DFS, was found to be ∼10 and ∼50%, respectively, confirming the high potential of DFS.

  6. Coarse-grain molecular dynamics simulations of diblock copolymer surfactants interacting with a lipid bilayer

    NASA Astrophysics Data System (ADS)

    Srinivas, Goundla; Klein, Michael L.

    2004-01-01

    The interaction of surfactant diblock poly(ethylene oxide)-poly(ethylethylene) copolymers (PEO-PEE) with a lipid bilayer of dimyristoylphosphatidylcholine has been studied by means of coarse-grain molecular dynamics simulations. The effect of the surfactants on the lipid bilayer was studied over a wide range of diblock copolymer concentrations. The simulations show that the hydrophilic PEO chains adopt different structures at low and high concentrations. In particular, the computed density profiles reveal that the PEO chains extend over a longer range from the bilayer surface, with increasing copolymer concentration. The simulated density profiles are in agreement with the scaling law predictions.

  7. Molecular dynamics simulation of the interactions between EHD1 EH domain and multiple peptides* #

    PubMed Central

    Yu, Hua; Wang, Mao-Jun; Xuan, Nan-Xia; Shang, Zhi-Cai; Wu, Jun

    2015-01-01

    Objective: To provide essential information for peptide inhibitor design, the interactions of Eps15 homology domain of Eps15 homology domain-containing protein 1 (EHD1 EH domain) with three peptides containing NPF (asparagine-proline-phenylalanine), DPF (aspartic acid-proline-phenylalanine), and GPF (glycine-proline-phenylalanine) motifs were deciphered at the atomic level. The binding affinities and the underlying structure basis were investigated. Methods: Molecular dynamics (MD) simulations were performed on EHD1 EH domain/peptide complexes for 60 ns using the GROMACS package. The binding free energies were calculated and decomposed by molecular mechanics/generalized Born surface area (MM/GBSA) method using the AMBER package. The alanine scanning was performed to evaluate the binding hot spot residues using FoldX software. Results: The different binding affinities for the three peptides were affected dominantly by van der Waals interactions. Intermolecular hydrogen bonds provide the structural basis of contributions of van der Waals interactions of the flanking residues to the binding. Conclusions: van der Waals interactions should be the main consideration when we design peptide inhibitors of EHD1 EH domain with high affinities. The ability to form intermolecular hydrogen bonds with protein residues can be used as the factor for choosing the flanking residues. PMID:26465136

  8. Fluorescence Correlation Spectroscopy Simulations of Photophysical Phenomena and Molecular Interactions: A Molecular Dynamics/Monte Carlo Approach

    PubMed Central

    Dix, James A.; Hom, Erik F. Y.; Verkman, A. S.

    2011-01-01

    Fluorescence correlation spectroscopy (FCS) is being applied increasingly to study diffusion and interactions of fluorescently labeled macromolecules in complex biological systems. Fluctuations in detected fluorescence, δF(t), are expressed as time-correlation functions, G(τ), and photon-count histograms, P(k;ΔT). Here, we developed a generalized simulation approach to compute G(τ) and P(k;ΔT) for complex systems with arbitrary geometry, photophysics, diffusion, and macromolecular interactions. G(τ) and P(k;ΔT) were computed from δF(t) generated by a Brownian dynamics simulation of single-molecule trajectories followed by a Monte Carlo simulation of fluorophore excitation and detection statistics. Simulations were validated by comparing analytical and simulated G(τ) and P(k;ΔT) for diffusion of noninteracting fluorophores in a three-dimensional Gaussian excitation and detection volume. Inclusion of photobleaching and triplet-state relaxation produced significant changes in G(τ) and P(k;ΔT). Simulations of macromolecular interactions and complex diffusion were done, including transient fluorophore binding to an immobile matrix, cross-correlation analysis of interacting fluorophores, and anomalous sub- and superdiffusion. The computational method developed here is generally applicable for simulating FCS measurements on systems complicated by fluorophore interactions or molecular crowding, and experimental protocols for which G(τ) and P(k;ΔT) cannot be computed analytically. PMID:16471761

  9. From protein denaturant to protectant: Comparative molecular dynamics study of alcohol/protein interactions

    NASA Astrophysics Data System (ADS)

    Shao, Qiang; Fan, Yubo; Yang, Lijiang; Qin Gao, Yi

    2012-03-01

    It is well known that alcohols can have strong effects on protein structures. For example, monohydric methanol and ethanol normally denature, whereas polyhydric glycol and glycerol protect, protein structures. In a recent combined theoretical and NMR experimental study, we showed that molecular dynamics simulations can be effectively used to understand the molecular mechanism of methanol denaturing protein. In this study, we used molecular dynamics simulations to investigate how alcohols with varied hydrophobicity and different numbers of hydrophilic groups (hydroxyl groups) exert effects on the structure of the model polypeptide, BBA5. First, we showed that methanol and trifluoroethanol (TFE) but not glycol or glycerol disrupt hydrophobic interactions. The latter two alcohols instead protect the assembly of the α- and β-domains of the polypeptide. Second, all four alcohols were shown to generally increase the stability of secondary structures, as revealed by the increased number of backbone hydrogen bonds formed in alcohol/water solutions compared to that in pure water, although individual hydrogen bonds can be weakened by certain alcohols, such as TFE. The two monohydric alcohols, methanol and TFE, display apparently different sequence-dependence in affecting the backbone hydrogen bond stability: methanol tends to enhance the stability of backbone hydrogen bonds of which the carbonyl groups are from polar residues, whereas TFE tends to stabilize those involving non-polar residues. These results demonstrated that subtle differences in the solution environment could have distinct consequences on protein structures.

  10. Molecular Dynamics Studies of Transportan 10 (Tp10) Interacting with a POPC Lipid Bilayer

    PubMed Central

    Dunkin, Christina M.; Pokorny, Antje; Almeida, Paulo F.; Lee, Hee-Seung

    2011-01-01

    We performed a series of molecular dynamics simulations to study the nature of interactions between transportan 10 (tp10) and a zwitterionic POPC bilayer. Tp10 is an amphipathic cell-penetrating peptide with a net positive charge of +5 and is known to adopt an α-helical secondary structure on the surface of POPC membranes. The study showed that tp10 preferentially binds to the membrane surface with its hydrophobic side facing the hydrophobic lipid core. Such orientation allows Lys residues, with positively charged long side chains, to stay in the polar environment during the insertion process. The simulations revealed that the Lys–phosphate salt bridge is a key factor in determining the orientation of the peptide in the interfacial region as well as in stabilizing the peptide-membrane interaction. The electrostatic attraction between Lys and phosphate groups is also believed to be the main bottleneck for the translocation of tp10 across the membrane. PMID:21194203

  11. Molecular dynamics simulation of interaction of H with vacancy in W

    SciTech Connect

    Li, Xiaochun; Gao, Fei; Lu, Guang-Hong

    2009-09-15

    Molecular dynamics simulations were performed to investigate the interaction between H and vacancy in W using an analytical bond-order potential to describe the interactions between W-W, W-H and H-H. The most stable configuration for H in W is the tetrahedron interstitial site. We calculated the binding energies of an H and a vacancy to an H-vacancy cluster (HnVm) in W, respectively, where n and m ranged from 0 to 10. The binding energy was almost unchanged. The binding energy of a vacancy to H-vacancy cluster is about 0.4eV, which is higher than the binding energy of an H to H-vacancy cluster. Vacancy is much easier to binding with H-vacancy cluster than H. And H is easier to stay in the tetrahedron interstitial site or octahedron interstitial site in bcc W.

  12. Replica Exchange Molecular Dynamics Study of Dimerization in Prion Protein: Multiple Modes of Interaction and Stabilization.

    PubMed

    Chamachi, Neharika G; Chakrabarty, Suman

    2016-08-01

    The pathological forms of prions are known to be a result of misfolding, oligomerization, and aggregation of the cellular prion. While the mechanism of misfolding and aggregation in prions has been widely studied using both experimental and computational tools, the structural and energetic characterization of the dimer form have not garnered as much attention. On one hand dimerization can be the first step toward a nucleation-like pathway to aggregation, whereas on the other hand it may also increase the conformational stability preventing self-aggregation. In this work, we have used extensive all-atom replica exchange molecular dynamics simulations of both monomer and dimer forms of a mouse prion protein to understand the structural, dynamic, and thermodynamic stability of dimeric prion as compared to the monomeric form. We show that prion proteins can dimerize spontaneously being stabilized by hydrophobic interactions as well as intermolecular hydrogen bonding and salt bridge formation. We have computed the conformational free energy landscapes for both monomer and dimer forms to compare the thermodynamic stability and misfolding pathways. We observe large conformational heterogeneity among the various modes of interactions between the monomers and the strong intermolecular interactions may lead to as high as 20% β-content. The hydrophobic regions in helix-2, surrounding coil regions, terminal regions along with the natively present β-sheet region appear to actively participate in prion-prion intermolecular interactions. Dimerization seems to considerably suppress the inherent dynamic instability observed in monomeric prions, particularly because the regions of structural frustration constitute the dimer interface. Further, we demonstrate an interesting reversible coupling between the Q160-G131 interaction (which leads to inhibition of β-sheet extension) and the G131-V161 H-bond formation. PMID:27390876

  13. Interactions of borneol with DPPC phospholipid membranes: a molecular dynamics simulation study.

    PubMed

    Yin, Qianqian; Shi, Xinyuan; Ding, Haiou; Dai, Xingxing; Wan, Guang; Qiao, Yanjiang

    2014-01-01

    Borneol, known as a "guide" drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol's penetration enhancing effect, the molecular basis of its action on bio-membranes is still unclear. We carried out a series of coarse-grained molecular dynamics simulations with the borneol concentration ranging from 3.31% to 54.59% (v/v, lipid-free basis) to study the interactions of borneol with aDPPC(1,2-dipalmitoylsn-glycero-3-phosphatidylcholine) bilayer membrane, and the temperature effects were also considered. At concentrations below 21.89%, borneol's presence only caused DPPC bilayer thinning and an increase in fluidity; A rise in temperature could promote the diffusing progress of borneol. When the concentration was 21.89% or above, inverted micelle-like structures were formed within the bilayer interior, which led to increased bilayer thickness, and an optimum temperature was found for the interaction of borneol with the DPPC bilayer membrane. These findings revealed that the choice of optimal concentration and temperature is critical for a given application in which borneol is used as a penetration enhancer. Our results not only clarify some molecular basis for borneol's penetration enhancing effects, but also provide some guidance for the development and applications of new preparations containing borneol. PMID:25383679

  14. Sodium ion interactions with aqueous glucose: insights from quantum mechanics, molecular dynamics, and experiment.

    PubMed

    Mayes, Heather B; Tian, Jianhui; Nolte, Michael W; Shanks, Brent H; Beckham, Gregg T; Gnanakaran, S; Broadbelt, Linda J

    2014-02-27

    In the last several decades, significant efforts have been conducted to understand the fundamental reactivity of glucose derived from plant biomass in various chemical environments for conversion to renewable fuels and chemicals. For reactions of glucose in water, it is known that inorganic salts naturally present in biomass alter the product distribution in various deconstruction processes. However, the molecular-level interactions of alkali metal ions and glucose are unknown. These interactions are of physiological interest as well, for example, as they relate to cation-glucose cotransport. Here, we employ quantum mechanics (QM) to understand the interaction of a prevalent alkali metal, sodium, with glucose from a structural and thermodynamic perspective. The effect on β-glucose is subtle: a sodium ion perturbs bond lengths and atomic partial charges less than rotating a hydroxymethyl group. In contrast, the presence of a sodium ion significantly perturbs the partial charges of α-glucose anomeric and ring oxygens. Molecular dynamics (MD) simulations provide dynamic sampling in explicit water, and both the QM and the MD results show that sodium ions associate at many positions with respect to glucose with reasonably equivalent propensity. This promiscuous binding nature of Na(+) suggests that computational studies of glucose reactions in the presence of inorganic salts need to ensure thorough sampling of the cation positions, in addition to sampling glucose rotamers. The effect of NaCl on the relative populations of the anomers is experimentally quantified with light polarimetry. These results support the computational findings that Na(+) interacts similarly with α- and β-glucose. PMID:24308866

  15. 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. PMID:25839357

  16. Molecular dynamics simulations of interfacial interactions between small nanoparticles during diffusion-limited aggregation

    NASA Astrophysics Data System (ADS)

    Lu, Jing; Liu, Dongmei; Yang, Xiaonan; Zhao, Ying; Liu, Haixing; Tang, Huan; Cui, Fuyi

    2015-12-01

    Due to the limitations of experimental methods at the atomic level, research on the aggregation of small nanoparticles (D < 5 nm) in aqueous solutions is quite rare. The aggregation of small nanoparticles in aqueous solutions is very different than that of normal sized nanoparticles. The interfacial interactions play a dominant role in the aggregation of small nanoparticles. In this paper, molecular dynamics simulations, which can explore the microscopic behavior of nanoparticles during the diffusion-limited aggregation at an atomic level, were employed to reveal the aggregation mechanism of small nanoparticles in aqueous solutions. First, the aggregation processes and aggregate structure were depicted. Second, the particle-particle interaction and surface diffusion of nanoparticles during aggregation were investigated. Third, the water-mediated interactions during aggregation were ascertained. The results indicate that the aggregation of nanoparticle in aqueous solutions is affected by particle size. The strong particle-particle interaction and high surface diffusion result in the formation of particle-particle bonds of 2 nm TiO2 nanoparticles, and the water-mediated interaction plays an important role in the aggregation process of 3 and 4 nm TiO2 nanoparticles.

  17. Deciphering the GPER/GPR30-agonist and antagonists interactions using molecular modeling studies, molecular dynamics, and docking simulations.

    PubMed

    Méndez-Luna, D; Martínez-Archundia, M; Maroun, Rachid C; Ceballos-Reyes, G; Fragoso-Vázquez, M J; González-Juárez, D E; Correa-Basurto, J

    2015-01-01

    The G-protein coupled estrogen receptor 1 GPER/GPR30 is a transmembrane seven-helix (7TM) receptor involved in the growth and proliferation of breast cancer. Due to the absence of a crystal structure of GPER/GPR30, in this work, molecular modeling studies have been carried out to build a three-dimensional structure, which was subsequently refined by molecular dynamics (MD) simulations (up to 120 ns). Furthermore, we explored GPER/GPR30's molecular recognition properties by using reported agonist ligands (G1, estradiol (E2), tamoxifen, and fulvestrant) and the antagonist ligands (G15 and G36) in subsequent docking studies. Our results identified the E2 binding site on GPER/GPR30, as well as other receptor cavities for accepting large volume ligands, through GPER/GPR30 π-π, hydrophobic, and hydrogen bond interactions. Snapshots of the MD trajectory at 14 and 70 ns showed almost identical binding motifs for G1 and G15. It was also observed that C107 interacts with the acetyl oxygen of G1 (at 14 ns) and that at 70 ns the residue E275 interacts with the acetyl group and with the oxygen from the other agonist whereas the isopropyl group of G36 is oriented toward Met141, suggesting that both C107 and E275 could be involved in the protein activation. This contribution suggest that GPER1 has great structural changes which explain its great capacity to accept diverse ligands, and also, the same ligand could be recognized in different binding pose according to GPER structural conformations. PMID:25587872

  18. Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular Interfaces of Protein-DNA Complexes.

    PubMed

    Chen, Chuanying; Esadze, Alexandre; Zandarashvili, Levani; Nguyen, Dan; Montgomery Pettitt, B; Iwahara, Junji

    2015-07-16

    Intermolecular ion pairs (salt bridges) are crucial for protein-DNA association. For two protein-DNA complexes, we demonstrate that the ion pairs of protein side-chain NH3+ and DNA phosphate groups undergo dynamic transitions between distinct states in which the charged moieties are either in direct contact or separated by water. While the crystal structures of the complexes show only the solvent-separated ion pair (SIP) state for some interfacial lysine side chains, our NMR hydrogen-bond scalar coupling data clearly indicate the presence of the contact ion pair (CIP) state for the same residues. The 0.6-μs molecular dynamics (MD) simulations confirm dynamic transitions between the CIP and SIP states. This behavior is consistent with our NMR order parameters and scalar coupling data for the lysine side chains. Using the MD trajectories, we also analyze the free energies of the CIP-SIP equilibria. This work illustrates the dynamic nature of short-range electrostatic interactions in DNA recognition by proteins. PMID:26207171

  19. Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular Interfaces of Protein–DNA Complexes

    PubMed Central

    2015-01-01

    Intermolecular ion pairs (salt bridges) are crucial for protein–DNA association. For two protein–DNA complexes, we demonstrate that the ion pairs of protein side-chain NH3+ and DNA phosphate groups undergo dynamic transitions between distinct states in which the charged moieties are either in direct contact or separated by water. While the crystal structures of the complexes show only the solvent-separated ion pair (SIP) state for some interfacial lysine side chains, our NMR hydrogen-bond scalar coupling data clearly indicate the presence of the contact ion pair (CIP) state for the same residues. The 0.6-μs molecular dynamics (MD) simulations confirm dynamic transitions between the CIP and SIP states. This behavior is consistent with our NMR order parameters and scalar coupling data for the lysine side chains. Using the MD trajectories, we also analyze the free energies of the CIP–SIP equilibria. This work illustrates the dynamic nature of short-range electrostatic interactions in DNA recognition by proteins. PMID:26207171

  20. Mechanism of MicroRNA-Target Interaction: Molecular Dynamics Simulations and Thermodynamics Analysis

    PubMed Central

    Wang, Yonghua; Li, Yan; Ma, Zhi; Yang, Wei; Ai, Chunzhi

    2010-01-01

    MicroRNAs (miRNAs) are endogenously produced ∼21-nt riboregulators that associate with Argonaute (Ago) proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target) and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1) three important (PAZ, Mid and PIWI) domains exist in Argonaute which define the global dynamics of the protein; 2) the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3) it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5′-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg2+) plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA). Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago. PMID:20686687

  1. Distal residue-CO interaction in carbonmonoxy myoglobins: a molecular dynamics study of three distal mutants.

    PubMed Central

    Jewsbury, P; Kitagawa, T

    1995-01-01

    Six 90-ps molecular dynamics trajectories, two for each of three distal mutants of sperm whale carbonmonoxy myoglobin, are reported; solvent waters within 16 A of the active site have been included. In both His64GIn trajectories, the distal side chain remains part of the heme pocket, forming a "closed" conformation similar to that of the wild type 64N delta H tautomer. Despite a connectivity more closely resembling the N epsilon H histidine tautomer, close interactions with the carbonyl ligand similar to those observed for the wild type 64N epsilon H tautomer are prevented in this mutant by repulsive interactions between the carbonyl O and the 64O epsilon. The aliphatic distal side chain of the His64Leu mutant shows little interaction with the carbonyl ligand in either His64Leu trajectory. Solvent water molecules move into and out of the active site in the His64Gly mutant trajectories; during all the other carbonmonoxy myoglobin trajectories, including the wild type distal tautomers considered in an earlier work, solvent molecules rarely encroach closer than 6 A of the active site. These results are consistent with a recent structural interpretation of the wild type infrared spectrum, and the current reinterpretation that the distal-ligand interaction in carbonmonoxy myoglobin is largely electrostatic, not steric, in nature. Images FIGURE 5 FIGURE 7 PMID:7787018

  2. Molecular dynamics of interactions of rice with rice blast and sheath blight pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In an effort to develop the molecular strategies to control rice (Oryzae sativa) diseases, molecular interactions of rice with rice blast [Magnaporthe oryzae, formerly (Magnaporthe grisea] and sheath blight (Rhizoctonia solani) fungi were analyzed. The interaction of rice with M. oryzae follows a b...

  3. Structure and Dynamics of Antifreeze Protein--Model Membrane Interactions: A Combined Spectroscopic and Molecular Dynamics Study.

    PubMed

    Kar, Rajiv K; Mroue, Kamal H; Kumar, Dinesh; Tejo, Bimo A; Bhunia, Anirban

    2016-02-11

    Antifreeze proteins (AFPs) are the key biomolecules that enable species to survive under subzero temperature conditions. The physiologically relevant activities of AFPs are based on the adsorption to ice crystals, followed by the inhibition of subsequent crystal layer growth of ice, routed with depression in freezing point in a noncolligative manner. The functional attributes governing the mechanism by which AFPs inhibit freezing of body fluids in bacteria, fungi, plants, and fishes are mainly attributed to their adsorption onto the surface of ice within the physiological system. Importantly, AFPs are also known for their application in cryopreservation of biological samples that might be related to membrane interaction. To date, there is a paucity of information detailing the interaction of AFPs with membrane structures. Here, we focus on elucidating the biophysical properties of the interactions between AFPs and micelle models that mimic the membrane system. Micelle model systems of zwitterionic DPC and negatively charged SDS were utilized in this study, against which a significant interaction is experienced by two AFP molecules, namely, Peptide 1m and wfAFP (the popular AFP sourced from winter flounder). Using low- and high-resolution biophysical characterization techniques, such as circular dichroism (CD) and NMR spectroscopy, a strong evidence for the interactions of these AFPs with the membrane models is revealed in detail and is corroborated by in-depth residue-specific information derived from molecular dynamics simulation. Altogether, these results not only strengthen the fact that AFPs interact actively with membrane systems, but also demonstrate that membrane-associated AFPs are dynamic and capable of adopting a number of conformations rendering fluidity to the system. PMID:26785292

  4. Molecular Dynamics Study of the Interactions Between Minerals and Gas Hydrate Species

    NASA Astrophysics Data System (ADS)

    Kvamme, B.; Leirvik, K. N.; Olsen, R.; Kuznetsova, T.

    2014-12-01

    The need for knowledge on gas hydrate "host" and "guest" interactions with reservoir rocks comes from the two folded exploitation of gas hydrates. On one hand natural gas hydrates represent an immense energy source, on the other hand carbon sequestration in the form of CO2 hydrates represents a long-term storage of carbon dioxide. Whether one's goal is to extract methane from natural gas hydrates or store carbon dioxide in the form of hydrates, it requires an understanding of the complex phenomena involving coupled dynamics of hydrates and hydrate stability in porous media. Hydrates can never attach directly to solid mineral surfaces because of the incompatibility of charges between the mineral surfaces and the hydrates. However, adsorption of water and carbon dioxide on mineral surfaces may favor heterogeneous nucleation of hydrate in the immediate vicinity. Different surfaces have their own specific adsorption preferences and corresponding adsorption thermodynamics. We have selected calcite, a common mineral found in porous media. Using molecular dynamics we have initially focused on the water interface in order to evaluate the "host" interactions towards the surface. We also aimed at evaluating the model before including guest molecules.

  5. Molecular dynamics simulations reveal specific interactions of post-translational palmitoyl modifications with rhodopsin in membranes

    PubMed Central

    Olausson, Bjoern E.S.; Grossfield, Alan; Pitman, Michael C.; Brown, Michael F.; Feller, Scott E.; Vogel, Alexander

    2012-01-01

    We present a detailed analysis of the behavior of the highly flexible post-translational lipid modifications of rhodopsin from multiple-microsecond all-atom molecular dynamics simulations. Rhodopsin was studied in a realistic membrane environment that includes cholesterol, as well as saturated and polyunsaturated lipids with phosphocholine and phosphoethanolamine headgroups. The simulation reveals striking differences between the palmitoylations at Cys322 and Cys323 as well as between the palmitoyl chains and the neighboring lipids. Notably the palmitoyl group at Cys322 shows considerably greater contact with helix H1 of rhodopsin, yielding frequent chain upturns with longer reorientational correlation times, and relatively low order parameters. While the palmitoylation at Cys323 makes fewer protein contacts and has increased order compared to Cys322, it nevertheless exhibits greater flexibility with smaller order parameters than the stearoyl chains of the surrounding lipids. The dynamical structure of the palmitoylations—as well as their extensive fluctuations—suggests a complex function for the post-translational modifications in rhodopsin and potentially other G protein-coupled receptors, going beyond their role as membrane anchoring elements. Rather, we propose that the palmitoylation at Cys323 has a potential role as a lipid anchor, whereas the palmitoyl-protein interaction observed for Cys322 suggests a more specific interaction that affects the stability of the dark state of rhodopsin. PMID:22280374

  6. CF interaction with Si(1 0 0)-(2 × 1): Molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Gou, F.; Gleeson, M. A.; Kleyn, A. W.

    2007-01-01

    In this study, the interaction of CF with the clean Si(1 0 0)-(2 × 1) surface at normal incidence and room temperature was investigated using molecular dynamics simulation. Incident energies of 2, 12 and 50 eV were simulated. C atoms, arising from dissociation, preferentially react with Si to form Si-C bonds. A Si xC yF z interfacial layer is formed, but no etching is observed. The interfacial layer thickness increases with increasing incident energy, mainly through enhanced penetration of the silicon lattice. Silicon carbide and fluorosilyl species are formed at 50 eV, which is in good agreement with available experimental data. The level of agreement between the simulated and experimental results is discussed.

  7. Shock wave interactions with nano-structured materials: a molecular dynamics approach

    NASA Astrophysics Data System (ADS)

    Al-Qananwah, A. K.; Koplik, J.; Andreopoulos, Y.

    2013-02-01

    Porous materials have long been known to be effective in blast mitigation strategies. Nano-structured materials appear to have an even greater potential for blast mitigation because of their high surface-to-volume ratio, a geometric factor which substantially attenuates shock wave propagation. A molecular dynamics approach was used to explore the effects of this remarkable property on the behavior of traveling shocks impacting on solid materials. The computational setup included a moving piston, a gas region, and a target solid wall with and without a porous structure. The materials involved were represented by realistic interaction potentials. The results indicate that the presence of a nano-porous material layer in front of the target wall reduced the stress magnitude and the energy deposited inside the solid by about 30 %, while at the same time substantially decreasing the loading rate.

  8. Characterization of Monobody Scaffold Interactions with Ligand via Force Spectroscopy and Steered Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Cheung, Luthur Siu-Lun; Shea, Daniel J.; Nicholes, Nathan; Date, Amol; Ostermeier, Marc; Konstantopoulos, Konstantinos

    2015-02-01

    Monobodies are antibody alternatives derived from fibronectin that are thermodynamically stable, small in size, and can be produced in bacterial systems. Monobodies have been engineered to bind a wide variety of target proteins with high affinity and specificity. Using alanine-scanning mutagenesis simulations, we identified two scaffold residues that are critical to the binding interaction between the monobody YS1 and its ligand, maltose-binding protein (MBP). Steered molecular dynamics (SMD) simulations predicted that the E47A and R33A mutations in the YS1 scaffold substantially destabilize the YS1-MBP interface by reducing the bond rupture force and the lifetime of single hydrogen bonds. SMD simulations further indicated that the R33A mutation weakens the hydrogen binding between all scaffold residues and MBP and not just between R33 and MBP. We validated the simulation data and characterized the effects of mutations on YS1-MBP binding by using single-molecule force spectroscopy and surface plasmon resonance. We propose that interfacial stability resulting from R33 of YS1 stacking with R344 of MBP synergistically stabilizes both its own bond and the interacting scaffold residues of YS1. Our integrated approach improves our understanding of the monobody scaffold interactions with a target, thus providing guidance for the improved engineering of monobodies.

  9. Characterization of monobody scaffold interactions with ligand via force spectroscopy and steered molecular dynamics.

    PubMed

    Cheung, Luthur Siu-Lun; Shea, Daniel J; Nicholes, Nathan; Date, Amol; Ostermeier, Marc; Konstantopoulos, Konstantinos

    2015-01-01

    Monobodies are antibody alternatives derived from fibronectin that are thermodynamically stable, small in size, and can be produced in bacterial systems. Monobodies have been engineered to bind a wide variety of target proteins with high affinity and specificity. Using alanine-scanning mutagenesis simulations, we identified two scaffold residues that are critical to the binding interaction between the monobody YS1 and its ligand, maltose-binding protein (MBP). Steered molecular dynamics (SMD) simulations predicted that the E47A and R33A mutations in the YS1 scaffold substantially destabilize the YS1-MBP interface by reducing the bond rupture force and the lifetime of single hydrogen bonds. SMD simulations further indicated that the R33A mutation weakens the hydrogen binding between all scaffold residues and MBP and not just between R33 and MBP. We validated the simulation data and characterized the effects of mutations on YS1-MBP binding by using single-molecule force spectroscopy and surface plasmon resonance. We propose that interfacial stability resulting from R33 of YS1 stacking with R344 of MBP synergistically stabilizes both its own bond and the interacting scaffold residues of YS1. Our integrated approach improves our understanding of the monobody scaffold interactions with a target, thus providing guidance for the improved engineering of monobodies. PMID:25650239

  10. Molecular Dynamics Simulation of Shock Waves Interacting with Nano-structures

    NASA Astrophysics Data System (ADS)

    Alqananwah, Ahmad; Koplik, Joel; Andreopoulos, Yiannis

    2009-11-01

    Typical theoretical treatments of shock wave interactions are based on a continuum approach, which cannot resolve the spatial variations in solids with nano-scale porous structure. To investigate such interactions we have developed a molecular dynamics simulation model, based on Lennard-Jones interactions. A piston, modeled as a uni-directional repulsive force field translating at a prescribed velocity, impinges on a region of gas which is compressed to form a shock, which in turn is driven against an atomistic solid wall. Periodic boundary conditions are used in the directions orthogonal to the piston motion, and we have considered solids based on either atoms tethered to lattice sites by stiff springs, or on embedded atom potentials. Velocity, temperature and stress fields are computed locally in both gas and solid regions, and displacements within the solid are interpreted in terms of its elastic constants. In this talk we present preliminary results, and the longer-term goal of this work is to understand energy transport and absorption in porous materials.

  11. 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. PMID:25340458

  12. Capsaicin interaction with TRPV1 channels in a lipid bilayer: molecular dynamics simulation.

    PubMed

    Hanson, Sonya M; Newstead, Simon; Swartz, Kenton J; Sansom, Mark S P

    2015-03-24

    Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel also involved in pain sensation, and is the receptor for capsaicin, the active ingredient of hot chili peppers. The recent structures of TRPV1 revealed putative ligand density within the S1 to S4 voltage-sensor-like domain of the protein. However, questions remain regarding the dynamic role of the lipid bilayer in ligand binding to TRPV1. Molecular dynamics simulations were used to explore behavior of capsaicin in a 1-palmitoyl-2-oleoyl phosphatidylcholine bilayer and with the target S1-S4 transmembrane helices of TRPV1. Equilibrium simulations reveal a preferred interfacial localization for capsaicin. We also observed a capsaicin molecule flipping from the extracellular to the intracellular leaflet, and subsequently able to access the intracellular TRPV1 binding site. Calculation of the potential of mean force (i.e., free energy profile) of capsaicin along the bilayer normal confirms that it prefers an interfacial localization. The free energy profile indicates that there is a nontrivial but surmountable barrier to the flipping of capsaicin between opposing leaflets of the bilayer. Molecular dynamics of the S1-S4 transmembrane helices of the TRPV1 in a lipid bilayer confirm that Y511, known to be crucial to capsaicin binding, has a distribution along the bilayer normal similar to that of the aromatic group of capsaicin. Simulations were conducted of the TRPV1 S1-S4 transmembrane helices in the presence of capsaicin placed in the aqueous phase, in the lipid, or docked to the protein. No stable interaction between ligand and protein was seen for simulations initiated with capsaicin in the bilayer. However, interactions were seen between TRPV1 and capsaicin starting from the cytosolic aqueous phase, and capsaicin remained stable in the majority of simulations from the docked pose. We discuss the significance of capsaicin flipping from the extracellular to the intracellular

  13. Molecular Dynamics Simulations of Amyloid β-Peptide (1-42): Tetramer Formation and Membrane Interactions.

    PubMed

    Brown, Anne M; Bevan, David R

    2016-09-01

    The aggregation cascade and peptide-membrane interactions of the amyloid β-peptide (Aβ) have been implicated as toxic events in the development and progression of Alzheimer's disease. Aβ42 forms oligomers and ultimately plaques, and it has been hypothesized that these oligomeric species are the main toxic species contributing to neuronal cell death. To better understand oligomerization events and subsequent oligomer-membrane interactions of Aβ42, we performed atomistic molecular-dynamics (MD) simulations to characterize both interpeptide interactions and perturbation of model membranes by the peptides. MD simulations were utilized to first show the formation of a tetramer unit by four separate Aβ42 peptides. Aβ42 tetramers adopted an oblate ellipsoid shape and showed a significant increase in β-strand formation in the final tetramer unit relative to the monomers, indicative of on-pathway events for fibril formation. The Aβ42 tetramer unit that formed in the initial simulations was used in subsequent MD simulations in the presence of a pure POPC or cholesterol-rich raft model membrane. Tetramer-membrane simulations resulted in elongation of the tetramer in the presence of both model membranes, with tetramer-raft interactions giving rise to the rearrangement of key hydrophobic regions in the tetramer and the formation of a more rod-like structure indicative of a fibril-seeding aggregate. Membrane perturbation by the tetramer was manifested in the form of more ordered, rigid membranes, with the pure POPC being affected to a greater extent than the raft membrane. These results provide critical atomistic insight into the aggregation pathway of Aβ42 and a putative toxic mechanism in the pathogenesis of Alzheimer's disease. PMID:27602722

  14. Interaction of the Disaccharide Trehalose with a Phospholipid Bilayer: A Molecular Dynamics Study

    PubMed Central

    Pereira, Cristina S.; Lins, Roberto D.; Chandrasekhar, Indira; Freitas, Luiz Carlos G.; Hünenberger, Philippe H.

    2004-01-01

    The disaccharide trehalose is well known for its bioprotective properties. Produced in large amounts during stress periods in the life of organisms able to survive potentially damaging conditions, trehalose plays its protective role by stabilizing biostructures such as proteins and lipid membranes. In this study, molecular dynamics simulations are used to investigate the interaction of trehalose with a phospholipid bilayer at atomistic resolution. Simulations of the bilayer in the absence and in the presence of trehalose at two different concentrations (1 or 2 molal) are carried out at 325 K and 475 K. The results show that trehalose is able to minimize the disruptive effect of the elevated temperature and stabilize the bilayer structure. At both temperature, trehalose is found to interact directly with the bilayer through hydrogen bonds. However, the water molecules at the bilayer surface are not completely replaced. At high temperature, the protective effect of trehalose is correlated with a significant increase in the number of trehalose-bilayer hydrogen bonds, predominantly through an increase in the number of trehalose molecules bridging three or more lipid molecules. PMID:15041666

  15. Interaction of dislocations with carbides in BCC Fe studied by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Granberg, F.; Terentyev, D.; Nordlund, K.

    2015-05-01

    In this study, the atomic processes involving the interaction of an edge dislocation with carbide precipitates in an iron matrix are investigated by molecular dynamics, utilizing two interatomic potentials (Hepburn, 2008 and Henriksson, 2013). The carbides investigated were Fe3 C and M23C6, where M was either Fe or Cr. The results from spherical precipitates were compared with rod shaped obstacles, to investigate the effect of climb in the unpinning process and the stress related to this process. The rod simulations showed a higher unpinning stress for all investigated sizes and temperatures, which indicates that climb will play a role in the unpinning phenomenon. The results showed, as previous studies, a decrease of the unpinning stress with increasing temperature and that a larger obstacle yields a higher unpinning stress. The Orowan process of dislocation unpinning was observed with both potentials as an increase in the needed unpinning stress in consecutive interactions with the same obstacle. The results showed that the structure of the obstacle does not affect the unpinning stress, as much as temperature, for obstacles ⩾ 2 nm. Comparison of obstacles with the same structure but with different composition, Fe23C6 and Cr23C6, showed that the small shearable chromium carbides were stronger than the corresponding iron carbides, pointing to the importance of the chemical composition of the carbide.

  16. Three-Dimensional FRET Reconstruction Microscopy for Analysis of Dynamic Molecular Interactions in Live Cells

    PubMed Central

    Hoppe, Adam D.; Shorte, Spencer L.; Swanson, Joel A.; Heintzmann, Rainer

    2008-01-01

    Analysis of cellular pathways requires concentration measurements of dynamically interacting molecules within the three-dimensional (3D) space of single living cells. Förster resonance energy transfer (FRET) microscopy from widefield, from confocal, and potentially from superresolution microscopes can access this information; however, these measurements are distorted by the inherent 3D blurring of optical imaging, spectral overlap of fluorophores, and detection noise. We propose a mathematical model of these processes and demonstrate, through simulation, how these distortions limit the dynamic range and sensitivity of conventional FRET microscopy. Using this model, we devise and validate a new approach (called 3D-FRET stoichiometry reconstruction, 3DFSR) for reconstructing 3D distributions of bound and free fluorescent molecules. Previous attempts to reconstruct 3D-FRET data relied on sequential spectral unmixing and deconvolution, a process that corrupts the detection statistics. We demonstrate that 3DFSR is superior to these approaches since it simultaneously models spectral mixing, optical blurring, and detection noise. To achieve the full potential of this technique, we developed an instrument capable of acquiring 3D-FRET data rapidly and sensitively from single living cells. Compared with conventional FRET microscopy, our 3D-FRET reconstruction technique and new instrumentation provides orders of magnitude gains in both sensitivity and accuracy wherein sustained high-resolution four-dimensional (x,y,z,t) imaging of molecular interactions inside living cells was achieved. These results verify previous observations that Cdc42 signaling is localized to the advancing margins of forming phagosomes in macrophages. PMID:18339754

  17. Molecular Dynamics Study of Interaction between Acrylamide Copolymers and Alumina Crystal

    NASA Astrophysics Data System (ADS)

    Wang, Feng-he; Wang, Feng-yun; Gong, Xue-dong

    2012-10-01

    Four acrylamide polymer flocculants, anionic polyacrylamide P(AA-co-AM), cationic polyacrylamide P(DMB-co-AM), nonionic polyacrylamide P(AM), and hydrophobical polyacrylamide P(OA-co-AM) have been prepared by copolymerizing with acrylic acid, cationic monomer dimethylethyl (acryloxyethyl) ammonium bromide (DMB) and hydrophobical monomer octadecyl acrylate with acrylamide. The interactions between the flocculants with the (012) surface of alumina crystal (Al2O3) have been simulated by molecular dynamics method. All the polymers can bind tightly with Al2O3 crystal, the interaction between the O of polymers and Al of the (012) surface of Al2O3 is significantly strong. The order of binding energy is as follows: P(DMB-co-AM)>P(OA-co-AM)>P(AA-co-AM)>P(AM), implying a better flocculation performance of P(DMB-co-AM) than the others. Analysis indicates that binding energy is mainly determined by Coulomb interaction. Bonds are found between the O atoms of the polymers and the Al atoms of Al2O3. The polymers' structures deform when they combine with Al2O3 crystal, but the deformation energies are low and far less than non-bonding energies. Flocculation experiments in suspension medium of 1%Kaolin show a transmittancy of 90.8% for 6 mg/L P(DMB-co-AM) and 73.0% for P(AM). The sequence of flocculation performance of four polymers is P(DMB-co-AM)>P(OA-co-AM)>P(AA-co-AM)>P(AM), which is in excellent agreement with the simulation results of binding energy.

  18. Estimation of the mutual orientation and intermolecular interaction of C12Ex from molecular dynamics simulations.

    PubMed

    Velinova, Maria; Tsoneva, Yana; Ivanova, Anela; Tadjer, Alia

    2012-04-26

    Nonionic surfactants, such as poly(ethylene glycol) alkyl ethers (abbreviated as CyEx) show a rich phase behavior in aqueous solution, i.e., they form micellar, lamellar, cubic, and so forth phases depending on experimental parameters such as the hydrophobic and hydrophilic chain lengths, temperature, or concentration. The aim of the present study is to determine the nature of the preaggregates, which are inferred to exist before the actual self-assembly process in aqueous solution, and to assess the aptitude to their formation. The target molecules are C12E3, C12E4 and C12E5, surfactants of moderate water solubility. Coarse-grained and all-atom molecular dynamics simulations (NPT/293 K) of two molecules of each species with explicit water in periodic boundary conditions are carried out to estimate the mutual orientation and the interaction between the surfactants in their dimers. The force fields are MARTINI and Amber99, the latter with self-derived parameters for the ether groups. The change in the orientation and distance between the molecules in the dimers are discussed based on different structural parameters. In addition, the interaction between the surfactants is evaluated from quantum chemistry calculations in terms of binding energy for the average structures from the cluster analysis. The solvent-solute interaction is quantified by the mean number of hydrogen bonds formed between them. On the basis of combined analysis, a series of different structures for subsequent study of the possible self-assembly patterns of C12E3, C12E4, and C12E5 is outlined. PMID:22448734

  19. Interaction of Curcumin with PEO-PPO-PEO block copolymers: a molecular dynamics study.

    PubMed

    Samanta, Susruta; Roccatano, Danilo

    2013-03-21

    Curcumin, a naturally occurring drug molecule, has been extensively investigated for its various potential usages in medicine. Its water insolubility and high metabolism rate require the use of drug delivery systems to make it effective in the human body. Among various types of nanocarriers, block copolymer based ones are the most effective. These polymers are broadly used as drug-delivery systems, but the nature of this process is poorly understood. In this paper, we propose a molecular dynamics simulation study of the interaction of Curcumin with block copolymer based on polyethylene oxide (PEO) and polypropylene oxide (PPO). The study has been conducted considering the smallest PEO and PPO oligomers and multiple chains of the block copolymer Pluronic P85. Our study shows that the more hydrophobic 1,2-dimethoxypropane (DMP) molecules and PPO block preferentially coat the Curcumin molecule. In the case of the Pluronic P85, simulation shows formation of a drug-polymer aggregate within 50 ns. This process leaves exposed the PEO part of the polymers, resulting in better solvation and stability of the drug in water. PMID:23441964

  20. Visualization for Molecular Dynamics Simulation of Gas and Metal Surface Interaction

    NASA Astrophysics Data System (ADS)

    Puzyrkov, D.; Polyakov, S.; Podryga, V.

    2016-02-01

    The development of methods, algorithms and applications for visualization of molecular dynamics simulation outputs is discussed. The visual analysis of the results of such calculations is a complex and actual problem especially in case of the large scale simulations. To solve this challenging task it is necessary to decide on: 1) what data parameters to render, 2) what type of visualization to choose, 3) what development tools to use. In the present work an attempt to answer these questions was made. For visualization it was offered to draw particles in the corresponding 3D coordinates and also their velocity vectors, trajectories and volume density in the form of isosurfaces or fog. We tested the way of post-processing and visualization based on the Python language with use of additional libraries. Also parallel software was developed that allows processing large volumes of data in the 3D regions of the examined system. This software gives the opportunity to achieve desired results that are obtained in parallel with the calculations, and at the end to collect discrete received frames into a video file. The software package "Enthought Mayavi2" was used as the tool for visualization. This visualization application gave us the opportunity to study the interaction of a gas with a metal surface and to closely observe the adsorption effect.

  1. Interactions of fatty acids with phosphatidylethanolamine membranes: X-ray diffraction and molecular dynamics studies

    PubMed Central

    Cordomí, Arnau; Prades, Jesús; Frau, Juan; Vögler, Oliver; Funari, Sérgio S.; Perez, Juan J.; Escribá, Pablo V.; Barceló, Francisca

    2010-01-01

    An experimental and theoretical study on 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) membranes containing fatty acids (FAs) was performed by means of X-ray diffraction analysis and molecular dynamics (MD) simulations. The study was aimed at understanding the interactions of several structurally related FAs with biomembranes, which is necessary for further rational lipid drug design in membrane-lipid therapy. The main effect of FAs was to promote the formation of a HII phase, despite a stabilization of the coexisting Lα + HII phases. Derivatives of OA exhibited a specific density profile in the direction perpendicular to the bilayer that reflects differences in the relative localization of the carboxylate group within the polar region of the membrane as well as in the degree of membrane penetration of the FA acyl chain. Hydroxyl and methyl substituents at carbon-2 in the FA acyl chain were identified as effective modulators of the position of carboxylate group in the lipid bilayer. Our data highlight the specific potential of each FA in modulating the membrane structure properties. PMID:19965616

  2. Binding interaction of SGLT with sugar and thiosugar by the molecular dynamics simulation.

    PubMed

    Tamura, Yunoshin; Miyagawa, Hiroh; Yoshida, Tatsusada; Chuman, Hiroshi

    2015-11-01

    The human sodium-glucose co-transporter 2 (hSGLT2) is a transporter responsible for reabsorption of glucose in the proximal convoluted tubule of the kidney. hSGLT2 inhibitors, including luseogliflozin, have been developed as drugs for type 2 diabetes mellitus. Only luseogliflozin contains a thiosugar ring in its chemical structure, while other hSGLT2 inhibitors contain glucose rings. Consequently, we focused on the binding interactions of hSGLT2 with sugars and thiosugars. We first revealed that the binding affinities of thiosugars are stronger than those of sugars through molecular dynamics simulations of Vibrio parahaemolyticus, sodium-galactose co-transporter, and human hSGLT2. We then demonstrated that Na(+) dissociates from the protein to the cytoplasmic solution more slowly in the thiosugar system than in the sugar system. These differences between sugars and thiosugars are discussed on the basis of the different binding modes due to the atom at the 5-position of the sugar and thiosugar rings. Finally, as a result of Na(+) dissociation, we suggest that the dissociation of thiosugars is slower than that of sugars. PMID:26260238

  3. Molecular dynamics investigation of the interaction of dislocations with carbides in BCC Fe

    NASA Astrophysics Data System (ADS)

    Granberg, F.; Terentyev, D.; Nordlund, K.

    2015-06-01

    Different types of carbides are present in many steels used as structural materials. To safely use steel in demanding environments, like nuclear power plants, it is important to know how defects will affect the mechanical properties of the material. In this study, the effect of carbide precipitates on the edge dislocation movement is investigated. Three different types of carbides were investigated by means of molecular dynamics, with a Tersoff-like bond order interatomic potential by Henriksson et al. The obstacles were 4 nm in diameter and were of Fe3C- (cementite-), Fe23C6- and Cr23C6-type. The critical unpinning stress was calculated for each type at different temperatures, to get the temperature-dependent obstacle strength. The results showed a decreasing critical stress with increasing temperature, consistent with previous studies. The critical unpinning stress was seen to be dependent on the type of carbide, but the differences were small. A difference was also observed between the obstacles with the same structure, but with different composition. This study shows the relation between the existing Cr23C6 carbide and the experimentally non-existing Fe23C6 carbide, which needs to be used as a model system for investigations with interatomic potentials not able to describe the interaction of Cr in the Fe-C-system. We found the difference to be a between 7% and 10% higher critical unpinning stress for the chromium carbide, than for the iron carbide of the same type.

  4. Dynamic, mechanistic, molecular-level modelling of cyanobacteria: Anabaena and nitrogen interaction.

    PubMed

    Hellweger, Ferdi L; Fredrick, Neil D; McCarthy, Mark J; Gardner, Wayne S; Wilhelm, Steven W; Paerl, Hans W

    2016-09-01

    Phytoplankton (eutrophication, biogeochemical) models are important tools for ecosystem research and management, but they generally have not been updated to include modern biology. Here, we present a dynamic, mechanistic, molecular-level (i.e. gene, transcript, protein, metabolite) model of Anabaena - nitrogen interaction. The model was developed using the pattern-oriented approach to model definition and parameterization of complex agent-based models. It simulates individual filaments, each with individual cells, each with genes that are expressed to yield transcripts and proteins. Cells metabolize various forms of N, grow and divide, and differentiate heterocysts when fixed N is depleted. The model is informed by observations from 269 laboratory experiments from 55 papers published from 1942 to 2014. Within this database, we identified 331 emerging patterns, and, excluding inconsistencies in observations, the model reproduces 94% of them. To explore a practical application, we used the model to simulate nutrient reduction scenarios for a hypothetical lake. For a 50% N only loading reduction, the model predicts that N fixation increases, but this fixed N does not compensate for the loading reduction, and the chlorophyll a concentration decreases substantially (by 33%). When N is reduced along with P, the model predicts an additional 8% reduction (compared to P only). PMID:27059435

  5. Electrostatic unfolding and interactions of albumin driven by pH changes: a molecular dynamics study.

    PubMed

    Baler, K; Martin, O A; Carignano, M A; Ameer, G A; Vila, J A; Szleifer, I

    2014-01-30

    A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation. PMID:24393011

  6. Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study

    PubMed Central

    2015-01-01

    A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation. PMID:24393011

  7. Molecular Dynamics Simulations of the Interactions Between Tungsten Dust and Beryllium Plasma-Facing Material

    NASA Astrophysics Data System (ADS)

    Niu, Guojian; Li, Xiaochun; Xu, Qian; Yang, Zhongshi; Luo, Guangnan

    2015-12-01

    In the present research, molecular dynamics simulation is applied to study the interactions between tungsten dusts and a beryllium plasma-facing material surface. Calculation results show that it is quite difficult for nanometer-size dust particles to damage the plasma-facing material surface, which is different from the micrometer-size ones. The reason may be the size difference between dust and crystal grains. The depth of dust penetration into plasma-facing materials is closely related to the incident velocity, and the impacting angle also plays an important role. Dust and material surface damage is also investigated. Results show that both incident velocity and angle can significantly influence the damage. supported by the National Magnetic Confinement Fusion Science Program of China (Nos. 2013GB105001, 2013GB105002, and 2015GB109001), National Natural Science Foundation of China (Nos. 11205198, 11305213 and 11405201), as well as Technological Development Grant of Hefei Science Center of CAS (No. 2014TDG-HSC003)

  8. Interactions of sarin with polyelectrolyte membranes: a molecular dynamics simulation study.

    PubMed

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Gor, Gennady Yu; Neimark, Alexander V

    2013-01-10

    Nanostructured polyelectrolyte membranes (PEMs), which are widely used as permselective diffusion barriers in fuel cell technologies and electrochemical processing, are considered as protective membranes suitable for blocking warfare toxins, including water-soluble nerve agents such as sarin. In this article, we examine the mechanisms of sorption and diffusion of sarin in hydrated PEMs by means of atomistic molecular dynamics simulations. Three PEMs are considered: Nafion, sulfonated polystyrene (sPS) that forms the hydrophilic subphase of segregated sPS-polyolefin block copolymers, and random sPS-polyethylene copolymer. We found that sarin concentrates at the interface between the hydrophilic and hydrophobic subphases of hydrated Nafion acting as a surfactant. In hydrated sPS, where the scale of water-polymer segregation is much smaller (1-2 nm), sarin also interacts favorably with hydrophobic and hydrophilic components. Water diffusion slows as the sarin content increases despite the overall increase in solvent content, which suggests that sarin and water have somewhat different pathways through the segregated membrane. Upon replacement of counterions of monovalent potassium with those of divalent calcium, sarin diffusion slows but remains substantial in all ionomers considered, especially at high sarin concentrations. The behavior of sarin is similar to that of its common simulant, dimethyl methylphosphonate. PMID:23205740

  9. Nature of protein-CO2 interactions as elucidated via molecular dynamics.

    PubMed

    Drummond, Michael L; Wilson, Angela K; Cundari, Thomas R

    2012-09-27

    Rising global temperatures require innovative measures to reduce atmospheric concentrations of CO(2). The most successful carbon capture technology on Earth is the enzymatic capture of CO(2) and its sequestration in the form of glucose. Efforts to improve upon or mimic this naturally occurring process will require a rich understanding of protein-CO(2) interactions. Toward that end, extensive all-atom molecular dynamics (MD) simulations were performed on the CO(2)-utilizing enzyme phosphoenolpyruvate carboxykinase (PEPCK). Preliminary simulations were performed using implicit and explicit solvent models, which yielded similar results: arginine, lysine, tyrosine, and asparagine enhance the ability of a protein to bind carbon dioxide. Extensive explicit solvent simulations were performed for both wild-type PEPCK and five single-point PEPCK mutants, revealing three prevalent channels by which CO(2) enters (or exits) the active site cleft, as well as a fourth channel (observed only once), the existence of which can be rationalized in terms of the position of a key Arg residue. The strongest CO(2) binding sites in these simulations consist of appropriately positioned hydrogen bond donors and acceptors. Interactions between CO(2) and both Mn(2+) and Mg(2+) present in PEPCK are minimal due to the stable protein- and solvent-based coordination environments of these cations. His 232, suggested by X-ray crystallography as being a potential important CO(2) binding site, is indeed found to be particularly "CO(2)-philic" in these simulations. Finally, a recent mechanism, proposed on the basis of X-ray crystallography, for PEPCK active site lid closure is discussed in light of the MD trajectories. Overall, the results of this work will prove useful not only to scientists investigating PEPCK, but also to groups seeking to develop an environmentally benign, protein-based carbon capture, sequestration, and utilization system. PMID:22882078

  10. A spectroscopic and molecular dynamic approach on the interaction between ionic liquid type gemini surfactant and human serum albumin.

    PubMed

    Maurya, Jitendra Kumar; Mir, Muzaffar Ul Hassan; Maurya, Neha; Dohare, Neeraj; Ali, Anwar; Patel, Rajan

    2016-10-01

    The interactions of imidazolium bashed ionic liquid-type cationic gemini surfactant ([C12-4-C12im]Br2) with HSA were studied by fluorescence, time-resolved fluorescence, UV-visible, circular dichroism, molecular docking and molecular dynamic simulation methods. The results showed that the [C12-4-C12im]Br2 quenched the fluorescence of HSA through dynamic quenching mechanism as confirmed by time-resolved spectroscopy. The Stern-Volmer quenching constant (Ksv) and relevant thermodynamic parameters such as enthalpy change (ΔH), Gibbs free energy change (ΔG) and entropy change (ΔS) for interaction system were calculated at different temperatures. The results revealed that hydrophobic forces played a major role in the interactions process. The results of synchronous fluorescence, UV-visible and CD spectra demonstrated that the binding of [C12-4-C12im]Br2 with HSA induces conformational changes in HSA. Inquisitively, the molecular dynamics study contribute towards understanding the effect of binding of [C12-4-C12im]Br2 on HSA to interpret the conformational change in HSA upon binding in aqueous solution. Moreover, the molecular modelling results show the possible binding sites in the interaction system. PMID:26473302

  11. Physical nature of intermolecular interactions inside Sir2 homolog active site: molecular dynamics and ab initio study.

    PubMed

    Czeleń, Przemysław; Czyżnikowska, Żaneta

    2016-06-01

    In the present study, we analyze the interactions of NAD+-dependent deacetylase (Sir2 homolog yeast Hst2) with carba-nicotinamide-adenine-dinucleotide (ADP-HPD). For the Sir2 homolog, a yeast Hst2 docking procedure was applied. The structure of the protein-ADP-HPD complex obtained during the docking procedure was used as a starting point for molecular dynamics simulation. The intermolecular interaction energy partitioning was performed for protein-ADP-HPD complex resulting from molecular dynamics simulation. The analysis was performed for ADP-HPD and 15 amino acids forming a deacetylase binding pocket. Although the results indicate that the first-order electrostatic interaction energy is substantial, the presence of multiple hydrogen bonds in investigated complexes can lead to significant value of induction component. PMID:27154340

  12. Importance of Three-Body Interactions in Molecular Dynamics Simulations of Water Demonstrated with the Fragment Molecular Orbital Method.

    PubMed

    Pruitt, Spencer R; Nakata, Hiroya; Nagata, Takeshi; Mayes, Maricris; Alexeev, Yuri; Fletcher, Graham; Fedorov, Dmitri G; Kitaura, Kazuo; Gordon, Mark S

    2016-04-12

    The analytic first derivative with respect to nuclear coordinates is formulated and implemented in the framework of the three-body fragment molecular orbital (FMO) method. The gradient has been derived and implemented for restricted second-order Møller-Plesset perturbation theory, as well as for both restricted and unrestricted Hartree-Fock and density functional theory. The importance of the three-body fully analytic gradient is illustrated through the failure of the two-body FMO method during molecular dynamics simulations of a small water cluster. The parallel implementation of the fragment molecular orbital method, its parallel efficiency, and its scalability on the Blue Gene/Q architecture up to 262 144 CPU cores are also discussed. PMID:26913837

  13. Interactions of anesthetics with the water-hexane interface. A molecular dynamics study

    NASA Technical Reports Server (NTRS)

    Chipot, C.; Wilson, M. A.; Pohorille, A.

    1997-01-01

    The free energy profiles characterizing the transfer of nine solutes across the liquid-vapor interfaces of water and hexane and across the water-hexane interface were calculated from molecular dynamics simulations. Among the solutes were n-butane and three of its halogenated derivatives, as well as three halogenated cyclobutanes. The two remaining molecules, dichlorodifluoromethane and 1,2-dichloroperfluoroethane, belong to series of halo-substituted methanes and ethanes, described in previous studies (J. Chem. Phys. 1996, 104, 3760; Chem. Phys. 1996, 204, 337). Each series of molecules contains structurally similar compounds that differ greatly in anesthetic potency. The accuracy of the simulations was tested by comparing the calculated and the experimental free energies of solvation of all nine compounds in water and in hexane. In addition. the calculated and the measured surface excess concentrations of n-butane at the water liquid-vapor interface were compared. In all cases, good agreement with experimental results was found. At the water-hexane interface, the free energy profiles for polar molecules exhibited significant interfacial minima, whereas the profiles for nonpolar molecules did not. The existence of these minima was interpreted in terms of a balance between the free energy contribution arising from solute-solvent interactions and the work to form a cavity that accommodates the solute. These two contributions change monotonically, but oppositely, across the interface. The interfacial solubilities of the solutes, obtained from the free energy profiles, correlate very well with their anesthetic potencies. This is the case even when the Meyer-Overton hypothesis, which predicts a correlation between anesthetic potency and solubility in oil, fails.

  14. Coarse-grained molecular dynamics simulations of depletion-induced interactions for soft matter systems

    SciTech Connect

    Shendruk, Tyler N.; Bertrand, Martin; Harden, James L.; Slater, Gary W.; Haan, Hendrick W. de

    2014-12-28

    Given the ubiquity of depletion effects in biological and other soft matter systems, it is desirable to have coarse-grained Molecular Dynamics (MD) simulation approaches appropriate for the study of complex systems. This paper examines the use of two common truncated Lennard-Jones (Weeks-Chandler-Andersen (WCA)) potentials to describe a pair of colloidal particles in a thermal bath of depletants. The shifted-WCA model is the steeper of the two repulsive potentials considered, while the combinatorial-WCA model is the softer. It is found that the depletion-induced well depth for the combinatorial-WCA model is significantly deeper than the shifted-WCA model because the resulting overlap of the colloids yields extra accessible volume for depletants. For both shifted- and combinatorial-WCA simulations, the second virial coefficients and pair potentials between colloids are demonstrated to be well approximated by the Morphometric Thermodynamics (MT) model. This agreement suggests that the presence of depletants can be accurately modelled in MD simulations by implicitly including them through simple, analytical MT forms for depletion-induced interactions. Although both WCA potentials are found to be effective generic coarse-grained simulation approaches for studying depletion effects in complicated soft matter systems, combinatorial-WCA is the more efficient approach as depletion effects are enhanced at lower depletant densities. The findings indicate that for soft matter systems that are better modelled by potentials with some compressibility, predictions from hard-sphere systems could greatly underestimate the magnitude of depletion effects at a given depletant density.

  15. Theory of polymer-nanopore interactions refined using molecular dynamics simulations.

    PubMed

    Balijepalli, Arvind; Robertson, Joseph W F; Reiner, Joseph E; Kasianowicz, John J; Pastor, Richard W

    2013-05-01

    Molecular dynamics simulations were used to refine a theoretical model that describes the interaction of single polyethylene glycol (PEG) molecules with α-hemolysin (αHL) nanopores. The simulations support the underlying assumptions of the model, that PEG decreases the pore conductance by binding cations (which reduces the number of mobile ions in the pore) and by volume exclusion, and provide bounds for fits to new experimental data. Estimation of cation binding indicates that four monomers coordinate a single K(+) in a crown-ether-like structure, with, on average, 1.5 cations bound to a PEG 29-mer at a bulk electrolyte concentration of 4 M KCl. Additionally, PEG is more cylindrical and has a larger cross-section area in the pore than in solution, although its volume is similar. Two key experimental quantities of PEG are described by the model: the ratio of single channel current in the presence of PEG to that in the polymer's absence (blockade depth) and the mean residence time of PEG in the pore. The refined theoretical model is simultaneously fit to the experimentally determined current blockade depth and the mean residence times for PEGs with 15 to 45 monomers, at applied transmembrane potentials of -40 to -80 mV and for three electrolyte concentrations. The model estimates the free energy of the PEG-cation complexes to be -5.3 kBT. Finally the entropic penalty of confining PEG to the pore is found to be inversely proportional to the electrolyte concentration. PMID:23590258

  16. Coarse-grained molecular dynamics simulations of depletion-induced interactions for soft matter systems

    NASA Astrophysics Data System (ADS)

    Shendruk, Tyler N.; Bertrand, Martin; Harden, James L.; Slater, Gary W.; de Haan, Hendrick W.

    2014-12-01

    Given the ubiquity of depletion effects in biological and other soft matter systems, it is desirable to have coarse-grained Molecular Dynamics (MD) simulation approaches appropriate for the study of complex systems. This paper examines the use of two common truncated Lennard-Jones (Weeks-Chandler-Andersen (WCA)) potentials to describe a pair of colloidal particles in a thermal bath of depletants. The shifted-WCA model is the steeper of the two repulsive potentials considered, while the combinatorial-WCA model is the softer. It is found that the depletion-induced well depth for the combinatorial-WCA model is significantly deeper than the shifted-WCA model because the resulting overlap of the colloids yields extra accessible volume for depletants. For both shifted- and combinatorial-WCA simulations, the second virial coefficients and pair potentials between colloids are demonstrated to be well approximated by the Morphometric Thermodynamics (MT) model. This agreement suggests that the presence of depletants can be accurately modelled in MD simulations by implicitly including them through simple, analytical MT forms for depletion-induced interactions. Although both WCA potentials are found to be effective generic coarse-grained simulation approaches for studying depletion effects in complicated soft matter systems, combinatorial-WCA is the more efficient approach as depletion effects are enhanced at lower depletant densities. The findings indicate that for soft matter systems that are better modelled by potentials with some compressibility, predictions from hard-sphere systems could greatly underestimate the magnitude of depletion effects at a given depletant density.

  17. Interaction of monovalent ions with the water liquid-vapor interface - A molecular dynamics study

    NASA Technical Reports Server (NTRS)

    Wilson, Michael A.; Pohorille, Andrew

    1991-01-01

    Results of molecular dynamics calculations are presented for a series of ions at infinite dilution near the water liquid-vapor interface. The free energies of ion transfer from the bulk to the interface are discussed, as are the accompanying changes of water structure at the surface and ion mobilities as a function of their proximity to the interface. It is shown that simple dielectric models do not provide an accurate description of ions at the water surface. The results of the study should be useful in the development of better models incorporating the shape and molecular structure of the interface.

  18. Dynamics and recognition within a protein–DNA complex: a molecular dynamics study of the SKN-1/DNA interaction

    PubMed Central

    Etheve, Loïc; Martin, Juliette; Lavery, Richard

    2016-01-01

    Molecular dynamics simulations of the Caenorhabditis elegans transcription factor SKN-1 bound to its cognate DNA site show that the protein–DNA interface undergoes significant dynamics on the microsecond timescale. A detailed analysis of the simulation shows that movements of two key arginine side chains between the major groove and the backbone of DNA generate distinct conformational sub-states that each recognize only part of the consensus binding sequence of SKN-1, while the experimentally observed binding specificity results from a time-averaged view of the dynamic recognition occurring within this complex. PMID:26721385

  19. Cyto•IQ: an adaptive cytometer for extracting the noisy dynamics of molecular interactions in live cells

    NASA Astrophysics Data System (ADS)

    Ball, David A.; Moody, Stephen E.; Peccoud, Jean

    2010-02-01

    We have developed a fundamentally new type of cytometer to track the statistics of dynamic molecular interactions in hundreds of individual live cells within a single experiment. This entirely new high-throughput experimental system, which we have named Cyto•IQ, reports statistical, rather than image-based data for a large cellular population. Like a flow cytometer, Cyto•IQ rapidly measures several fluorescent probes in a large population of cells to yield a reduced statistical model that is matched to the experimental goals set by the user. However, Cyto•IQ moves beyond flow cytometry by tracking multiple probes in individual cells over time. Using adaptive learning algorithms, we process data in real time to maximize the convergence of the statistical model parameter estimators. Software controlling Cyto•IQ integrates existing open source applications to interface hardware components, process images, and adapt the data acquisition strategy based on previously acquired data. These innovations allow the study of larger populations of cells, and molecular interactions with more complex dynamics, than is possible with traditional microscope-based approaches. Cyto•IQ supports research to characterize the noisy dynamics of molecular interactions controlling biological processes.

  20. The Dynamics of Molecular Interactions and Chemical Reactions at Metal Surfaces: Testing the Foundations of Theory

    NASA Astrophysics Data System (ADS)

    Golibrzuch, Kai; Bartels, Nils; Auerbach, Daniel J.; Wodtke, Alec M.

    2015-04-01

    We review studies of molecular interactions and chemical reactions at metal surfaces, emphasizing progress toward a predictive theory of surface chemistry and catalysis. For chemistry at metal surfaces, a small number of central approximations are typically made: (a) the Born-Oppenheimer approximation of electronic adiabaticity, (b) the use of density functional theory at the generalized gradient approximation level, (c) the classical approximation for nuclear motion, and (d) various reduced-dimensionality approximations. Together, these approximations constitute a provisional model for surface chemical reactivity. We review work on some carefully studied examples of molecules interacting at metal surfaces that probe the validity of various aspects of the provisional model.

  1. The dynamics of molecular interactions and chemical reactions at metal surfaces: testing the foundations of theory.

    PubMed

    Golibrzuch, Kai; Bartels, Nils; Auerbach, Daniel J; Wodtke, Alec M

    2015-04-01

    We review studies of molecular interactions and chemical reactions at metal surfaces, emphasizing progress toward a predictive theory of surface chemistry and catalysis. For chemistry at metal surfaces, a small number of central approximations are typically made: (a) the Born-Oppenheimer approximation of electronic adiabaticity, (b) the use of density functional theory at the generalized gradient approximation level, (c) the classical approximation for nuclear motion, and (d) various reduced-dimensionality approximations. Together, these approximations constitute a provisional model for surface chemical reactivity. We review work on some carefully studied examples of molecules interacting at metal surfaces that probe the validity of various aspects of the provisional model. PMID:25580627

  2. Molecular dynamics approaches to the design and synthesis of PCB targeting molecularly imprinted polymers: interference to monomer-template interactions in imprinting of 1,2,3-trichlorobenzene.

    PubMed

    Cleland, Dougal; Olsson, Gustaf D; Karlsson, Björn C G; Nicholls, Ian A; McCluskey, Adam

    2014-02-01

    The interactions between each component of the pre-polymerisation mixtures used in the synthesis of molecularly imprinted polymers (MIP) specific for 1,2,3,4,5-pentachlorobenzene (1) and 1,2,3-trichlorobenzene (2) were examined in four molecular dynamics simulations. These simulations revealed that the relative frequency of functional monomer-template (FM-T) interactions was consistent with results obtained by the synthesis and evaluation of the actual MIPs. The higher frequency of 1 interaction with trimethylstyrene (TMS; 54.7%) than 1 interaction with pentafluorostyrene (PFS; 44.7%) correlated with a higher imprinting factor (IF) of 2.1 vs. 1.7 for each functional monomer respectively. The higher frequency of PFS interactions with 2 (29.6%) than TMS interactions with 2 (1.9%) also correlated well with the observed differences in IF (3.7) of 2 MIPs imprinted using PFS as the FM than the IF (2.8) of 2 MIPs imprinted using TMS as the FM. The TMS-1 interaction dominated the molecular simulation due to high interaction energies, but the weaker TMS-2 resulted in low interaction maintenance, and thus lower IF values. Examination of the other pre-polymerisation mixture components revealed that the low levels of TMS-2 interaction was, in part, due to interference caused by the cross linker (CL) ethyleneglycol dimethylacrylate (EGDMA) interactions with TMS. The main reason was, however, attributed to MeOH interactions with TMS in both a hydrogen bond and perpendicular configuration. This positioned a MeOH directly above the π-orbital of all TMS for an average of 63.8% of MD2 creating significant interference to π-π stacking interactions between 2 and TMS. These findings are consistent with the deviation from the 'normal' molecularly imprinted polymer synthesis ratio of 1 : 4 : 20 (T : FM : CL) of 20 : 1 : 29 and 15 : 6 : 29 observed with 2 and TMS and PFS respectively. Our molecular dynamics simulations correctly predicted the high level

  3. Relevant interactions of antimicrobial iron chelators and membrane models revealed by nuclear magnetic resonance and molecular dynamics simulations.

    PubMed

    Coimbra, João T S; Moniz, Tânia; Brás, Natércia F; Ivanova, Galya; Fernandes, Pedro A; Ramos, Maria J; Rangel, Maria

    2014-12-18

    The dynamics and interaction of 3-hydroxy-4-pyridinone fluorescent iron chelators, exhibiting antimicrobial properties, with biological membranes were evaluated through NMR and molecular dynamics simulations. Both NMR and MD simulation results support a strong interaction of the chelators with the lipid bilayers that seems to be strengthened for the rhodamine containing compounds, in particular for compounds that include ethyl groups and a thiourea link. For the latter type of compounds the interaction reaches the hydrophobic core of the lipid bilayer. The molecular docking and MD simulations performed for the potential interaction of the chelators with DC-SIGN receptors provide valuable information regarding the cellular uptake of these compounds since the results show that the fluorophore fragment of the molecular framework is essential for an efficient binding. Putting together our previous and present results, we put forward the hypothesis that all the studied fluorescent chelators have access to the cell, their uptake occurs through different pathways and their permeation properties correlate with a better access to the cell and its compartments and, consequently, with the chelators antimicrobial properties. PMID:25482538

  4. Modulation of amphotericin B membrane interaction by cholesterol and ergosterol--a molecular dynamics study.

    PubMed

    Czub, Jacek; Baginski, Maciej

    2006-08-24

    Amphotericin B (AmB) is a well-known polyene macrolide antibiotic used to treat systemic fungal infections. According to a well-documented hypothesis, molecules of AmB form ionic membrane channels that are responsible for chemotherapeutic action. These channels disturb the barrier function of the cell membrane which, in consequence, leads to cell death. The presence of sterols in the cell membrane is necessary for full manifestation of the antibiotic's ionophoric activity, at least in vivo. Ergosterol-containing fungal membranes are targeted more efficiently by AmB than mammalian membranes containing cholesterol. However, a similar level of disturbance of fungal and mammalian membranes is responsible for serious toxicity of the antibiotic. Due to the importance of AmB and lack of better antifungal alternatives, the search for new less toxic derivatives of this antibiotic still continues. Therefore, studies of the AmB-membrane interaction are very important. The present work constitutes a continuation of a broad program of study on AmB mode of action in our group. In particular, molecular dynamics simulations of AmB monomers inside the bilayers of three different compositions (pure dimiristoylphosphatidylcholine (DMPC) and DMPC bilayer containing approximately 25 mol % of cholesterol or ergosterol) were carried out. In general, analysis of generated trajectories resulted in identifying many significant differences in the behavior of AmB monomers depending on the membrane environment. In particular, it was established that the antibiotic increases the internal order of DMPC bilayer containing 25 mol % of cholesterol, while it has no effect on the order of the bilayer with the same amount of ergosterol. Performed calculations also revealed that relatively rigid and elongated AmB molecules exhibit higher affinity toward the sterol-containing lo phases and, therefore, may be cumulated in ordered membrane domains (e.g., lipid rafts). Since the partition coefficient

  5. Accelerated molecular dynamics methods

    SciTech Connect

    Perez, Danny

    2011-01-04

    The molecular dynamics method, although extremely powerful for materials simulations, is limited to times scales of roughly one microsecond or less. On longer time scales, dynamical evolution typically consists of infrequent events, which are usually activated processes. This course is focused on understanding infrequent-event dynamics, on methods for characterizing infrequent-event mechanisms and rate constants, and on methods for simulating long time scales in infrequent-event systems, emphasizing the recently developed accelerated molecular dynamics methods (hyperdynamics, parallel replica dynamics, and temperature accelerated dynamics). Some familiarity with basic statistical mechanics and molecular dynamics methods will be assumed.

  6. Small molecule interactions with lipid bilayers: a molecular dynamics study of chlorhexidine

    NASA Astrophysics Data System (ADS)

    van Oosten, Brad; Marquardt, Drew; Sternin, Edward; Harroun, Thad

    2013-03-01

    Chlorhexidine presents an interesting modelling challenge with a hydrophobic hexane connecting two biguanides (arginine analogues) and two aromatic rings. We conducted molecular dynamic simulations using the GROMACS simulation software to reproduce the experimental environment of chlorhexidine in a 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) bilayer to produce atomic-level information. We constructed an all-atom force field of chlorhexidine from the CHARMM36 force field using well established parameters of certain amino acids. Partial charges were treated differently, which were calculated using GAUSSIAN software. We will compare and contrast the results of our model to that of our neutron scattering experiments previously done in our lab.

  7. Molecular docking and dynamics simulations on the interaction of cationic porphyrin-anthraquinone hybrids with DNA G-quadruplexes.

    PubMed

    Arba, Muhammad; Kartasasmita, Rahmana E; Tjahjono, Daryono H

    2016-01-01

    A series of cationic porphyrin-anthraquinone hybrids bearing either pyridine, imidazole, or pyrazole rings at the meso-positions have been investigated for their interaction with DNA G-quadruplexes by employing molecular docking and molecular dynamics simulations. Three types of DNA G-quadruplexes were utilized, which comprise parallel, antiparallel, and mixed hybrid topologies. The porphyrin hybrids have a preference to bind with parallel and mixed hybrid structures compared to the antiparallel structure. This preference arises from the end stacking of porphyrin moiety following G-stem and loop binding of anthraquinone tail, which is not found in the antiparallel due to the presence of diagonal and lateral loops that crowd the G-quartet. The binding to the antiparallel, instead, occurred with poorer affinity through both the loop and wide groove. All sites of porphyrin binding were confirmed by 6 ns molecular dynamics simulation, as well as by the negative value of the total binding free energies that were calculated using the MMPBSA method. Free energy analysis shows that the favorable contribution came from the electrostatic term, which supposedly originated from the interaction of either cationic pyridinium, pyrazole, or imidazole groups and the anionic phosphate backbone, and also from the van der Waals energy, which primarily contributed through end stacking interaction. PMID:25808513

  8. The effect of stacking fault energy on interactions between an edge dislocation and a spherical void by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Asari, K.; Hetland, O. S.; Fujita, S.; Itakura, M.; Okita, T.

    2013-11-01

    Molecular dynamics simulations were conducted using a set of six interatomic potentials for FCC metals that differed only in stacking fault energy (SFE), to clarify the effect of SFE on interactions between a dissociated edge dislocation and a void. There are two different types of interaction mechanism: separate depinning of the individual partial dislocations and almost simultaneous depinning of the combined partial dislocations. The interaction mechanism depends on both the SFE and void size, and changes the absolute value of the critical resolved shear stress (CRSS) and its dependence on the SFE. In the separate depinning case, the CRSS is relatively low and is almost independent of the SFE, while in the simultaneous case, the CRSS is increases with SFE. The void size for which the change in interaction mechanism occurs increases with decreasing SFE.

  9. Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis

    PubMed Central

    Cho, Kwang-Hyun

    2015-01-01

    From the perspective of systems science, tumorigenesis can be hypothesized as a critical transition (an abrupt shift from one state to another) between proliferative and apoptotic attractors on the state space of a molecular interaction network, for which an attractor is defined as a stable state to which all initial states ultimately converge, and the region of convergence is called the basin of attraction. Before the critical transition, a cellular state might transit between the basin of attraction for an apoptotic attractor and that for a proliferative attractor due to the noise induced by the inherent stochasticity in molecular interactions. Such a flickering state transition (state transition between the basins of attraction for alternative attractors from the impact of noise) would become more frequent as the cellular state approaches near the boundary of the basin of attraction, which can increase the variation in the estimate of the respective basin size. To investigate this for colorectal tumorigenesis, we have constructed a stochastic Boolean network model of the molecular interaction network that contains an important set of proteins known to be involved in cancer. In particular, we considered 100 representative sequences of 20 gene mutations that drive colorectal tumorigenesis. We investigated the appearance of cancerous cells by examining the basin size of apoptotic, quiescent, and proliferative attractors along with the sequential accumulation of gene mutations during colorectal tumorigenesis. We introduced a measure to detect the flickering state transition as the variation in the estimate of the basin sizes for three-phenotype attractors from the impact of noise. Interestingly, we found that this measure abruptly increases before a cell becomes cancerous during colorectal tumorigenesis in most of the gene mutation sequences under a certain level of stochastic noise. This suggests that a frequent flickering state transition can be a precritical

  10. Capturing a Dynamic Chaperone-Substrate Interaction Using NMR-Informed Molecular Modeling.

    PubMed

    Salmon, Loïc; Ahlstrom, Logan S; Horowitz, Scott; Dickson, Alex; Brooks, Charles L; Bardwell, James C A

    2016-08-10

    Chaperones maintain a healthy proteome by preventing aggregation and by aiding in protein folding. Precisely how chaperones influence the conformational properties of their substrates, however, remains unclear. To achieve a detailed description of dynamic chaperone-substrate interactions, we fused site-specific NMR information with coarse-grained simulations. Our model system is the binding and folding of a chaperone substrate, immunity protein 7 (Im7), with the chaperone Spy. We first used an automated procedure in which NMR chemical shifts inform the construction of system-specific force fields that describe each partner individually. The models of the two binding partners are then combined to perform simulations on the chaperone-substrate complex. The binding simulations show excellent agreement with experimental data from multiple biophysical measurements. Upon binding, Im7 interacts with a mixture of hydrophobic and hydrophilic residues on Spy's surface, causing conformational exchange within Im7 to slow down as Im7 folds. Meanwhile, the motion of Spy's flexible loop region increases, allowing for better interaction with different substrate conformations, and helping offset losses in Im7 conformational dynamics that occur upon binding and folding. Spy then preferentially releases Im7 into a well-folded state. Our strategy has enabled a residue-level description of a dynamic chaperone-substrate interaction, improving our understanding of how chaperones facilitate substrate folding. More broadly, we validate our approach using two other binding partners, showing that this approach provides a general platform from which to investigate other flexible biomolecular complexes through the integration of NMR data with efficient computational models. PMID:27415450

  11. Ab initio molecular dynamics simulations of ion-solid interactions in zirconate pyrochlores

    DOE PAGESBeta

    Xiao, Haiyan Y.; Weber, William J.; Zhang, Yanwen; Zu, X. T.

    2015-01-31

    In this paper, an ab initio molecular dynamics method is employed to study low energy recoil events in zirconate pyrochlores (A2Zr2O7, A = La, Nd and Sm). It shows that both cations and anions in Nd2Zr2O7 and Sm2Zr2O7 are generally more likely to be displaced than those in La2Zr2O7. The damage end states mainly consist of Frenkel pair defects, and the Frenkel pair formation energies in Nd2Zr2O7 and Sm2Zr2O7 are lower than those in La2Zr2O7. These results suggest that the order–disorder structural transition more easily occurs in Nd2Zr2O7 and Sm2Zr2O7 resulting in a defect-fluorite structure, which agrees well with experimentalmore » observations. Our calculations indicate that oxygen migration from 48f and 8b to 8a sites is dominant under low energy irradiation. A number of new defects, including four types of cation Frenkel pairs and six types of anion Frenkel pairs, are revealed by ab initio molecular dynamics simulations. The present findings may help to advance the fundamental understanding of the irradiation response behavior of zirconate pyrochlores.« less

  12. Molecular dynamics simulations of formamide interaction with hydrocyanic acid on a catalytic surface TiO2

    NASA Astrophysics Data System (ADS)

    Artoshina, O. V.; Vorob'eva, M. Yu.; Dushanov, E. B.; Kholmurodov, Kh. T.

    2014-06-01

    The behavior of water—formamide and hydrocyanic acid—formamide solutions on an anatase surface have been studied using molecular dynamics (MD) simulation method. The interaction activation energies have been estimated for the temperature range from 250 up to 400 K. The diffusion coefficients and structural radial distribution functions have been calculated for the formamide, water and hydrocyanic acid on an anatase surface. The calculated activation energies of the water—formamide—anatase and hydrocyanic acid—formamide—anatase systems were analyzed and compared. A comparative analysis of the systems under investigation was performed and a possible correlation between the obtained MD results and the molecular mechanism involving the formamide's interaction with dioxide titan adsorbing surface were discussed.

  13. Inelastic Neutron Scattering and Molecular Dynamics Determination of the Interaction Potential in Liquid CD{sub 4}

    SciTech Connect

    Guarini, E.; Barocchi, F.

    2007-10-19

    Anisotropic interactions of liquid CD{sub 4} are studied in detail by comparison of inelastic neutron Brillouin scattering data with molecular dynamics simulations using up to four different models of the methane site-site potential. We demonstrate that the experimental dynamic structure factor S(Q,{omega}) acts as a highly discriminating quantity for possible interaction schemes. In particular, the Q evolution of the spectra enables a selective probing of the short- and medium-range features of the anisotropic potentials. We show that the preferential configuration of methane dimers at liquid densities can thus be discerned by analyzing the orientation-dependent model potential curves, in light of the experimental and simulation results.

  14. Multiscale reactive molecular dynamics

    NASA Astrophysics Data System (ADS)

    Knight, Chris; Lindberg, Gerrick E.; Voth, Gregory A.

    2012-12-01

    Many processes important to chemistry, materials science, and biology cannot be described without considering electronic and nuclear-level dynamics and their coupling to slower, cooperative motions of the system. These inherently multiscale problems require computationally efficient and accurate methods to converge statistical properties. In this paper, a method is presented that uses data directly from condensed phase ab initio simulations to develop reactive molecular dynamics models that do not require predefined empirical functions. Instead, the interactions used in the reactive model are expressed as linear combinations of interpolating functions that are optimized by using a linear least-squares algorithm. One notable benefit of the procedure outlined here is the capability to minimize the number of parameters requiring nonlinear optimization. The method presented can be generally applied to multiscale problems and is demonstrated by generating reactive models for the hydrated excess proton and hydroxide ion based directly on condensed phase ab initio molecular dynamics simulations. The resulting models faithfully reproduce the water-ion structural properties and diffusion constants from the ab initio simulations. Additionally, the free energy profiles for proton transfer, which is sensitive to the structural diffusion of both ions in water, are reproduced. The high fidelity of these models to ab initio simulations will permit accurate modeling of general chemical reactions in condensed phase systems with computational efficiency orders of magnitudes greater than currently possible with ab initio simulation methods, thus facilitating a proper statistical sampling of the coupling to slow, large-scale motions of the system.

  15. Multiscale reactive molecular dynamics

    PubMed Central

    Knight, Chris; Lindberg, Gerrick E.; Voth, Gregory A.

    2012-01-01

    Many processes important to chemistry, materials science, and biology cannot be described without considering electronic and nuclear-level dynamics and their coupling to slower, cooperative motions of the system. These inherently multiscale problems require computationally efficient and accurate methods to converge statistical properties. In this paper, a method is presented that uses data directly from condensed phase ab initio simulations to develop reactive molecular dynamics models that do not require predefined empirical functions. Instead, the interactions used in the reactive model are expressed as linear combinations of interpolating functions that are optimized by using a linear least-squares algorithm. One notable benefit of the procedure outlined here is the capability to minimize the number of parameters requiring nonlinear optimization. The method presented can be generally applied to multiscale problems and is demonstrated by generating reactive models for the hydrated excess proton and hydroxide ion based directly on condensed phase ab initio molecular dynamics simulations. The resulting models faithfully reproduce the water-ion structural properties and diffusion constants from the ab initio simulations. Additionally, the free energy profiles for proton transfer, which is sensitive to the structural diffusion of both ions in water, are reproduced. The high fidelity of these models to ab initio simulations will permit accurate modeling of general chemical reactions in condensed phase systems with computational efficiency orders of magnitudes greater than currently possible with ab initio simulation methods, thus facilitating a proper statistical sampling of the coupling to slow, large-scale motions of the system. PMID:23249062

  16. Unveiling the complex network of interactions in Ionic Liquids: a combined EXAFS and Molecular Dynamics approach

    NASA Astrophysics Data System (ADS)

    Serva, A.; Migliorati, V.; Lapi, A.; D'Angelo, P.

    2016-05-01

    The structural properties of geminal dicationic ionic liquids ([Cn (mim)2]Br2)/water mixtures have been investigated by means of extended X-ray absorption fine structure (EXAFS) spectroscopy and Molecular Dynamics (MD) simulations. This synergic approach allowed us to assess the reliability of the MD results and to provide accurate structural information about the first coordination shell of the Br- ion. We found that the local environment around the anion changes as a function of the water concentration, while it is the same independently from the length of the bridge-alkyl chain. Moreover, as regards the long-range structural organization, no tail-tail aggregation occurs with increasing alkyl chain length.

  17. Characterizing the Free-Energy Landscape of MDM2 Protein-Ligand Interactions by Steered Molecular Dynamics Simulations.

    PubMed

    Hu, Guodong; Xu, Shicai; Wang, Jihua

    2015-12-01

    Inhibition of p53-MDM2 interaction by small molecules is considered to be a promising approach to re-activate wild-type p53 for tumor suppression. Several inhibitors of the MDM2-p53 interaction were designed and studied by the experimental methods and the molecular dynamics simulation. However, the unbinding mechanism was still unclear. The steered molecular dynamics simulations combined with Brownian dynamics fluctuation-dissipation theorem were employed to obtain the free-energy landscape of unbinding between MDM2 and their four ligands. It was shown that compounds 4 and 8 dissociate faster than compounds 5 and 7. The absolute binding free energies for these four ligands are in close agreement with experimental results. The open movement of helix II and helix IV in the MDM2 protein-binding pocket upon unbinding is also consistent with experimental MDM2-unbound conformation. We further found that different binding mechanisms among different ligands are associated with H-bond with Lys51 and Glu25. These mechanistic results may be useful for improving ligand design. PMID:26032728

  18. Interaction between Pin1 and its natural product inhibitor epigallocatechin-3-gallate by spectroscopy and molecular dynamics simulations.

    PubMed

    Xi, Lei; Wang, Yu; He, Qing; Zhang, Qingyan; Du, Linfang

    2016-12-01

    The binding of epigallocatechin-3-gallate (EGCG) to wild type Pin1 in solution was studied by spectroscopic methods and molecular dynamics simulations in this research to explore the binding mode and inhibition mechanism. The binding constants and number of binding sites per Pin1 for EGCG were calculated through the Stern-Volmer equation. The values of binding free energy and thermodynamic parameters were calculated and indicated that hydrogen bonds, electrostatic interaction and Van der Waals interaction played the major role in the binding process. The alterations of Pin1 secondary structure in the presence of EGCG were confirmed by far-UV circular dichroism spectra. The binding model at atomic-level revealed that EGCG was bound to the Glu12, Lys13, Arg14, Met15 and Arg17 in WW domain. Furthermore, EGCG could also interact with Arg69, Asp112, Cys113 and Ser114 in PPIase domain. PMID:27372509

  19. Calculation of adsorption free energy for solute-surface interactions using biased replica-exchange molecular dynamics

    PubMed Central

    Wang, Feng; Stuart, Steven J.; Latour, Robert A.

    2009-01-01

    The adsorption behavior of a biomolecule, such as a peptide or protein, to a functionalized surface is of fundamental importance for a broad range of applications in biotechnology. The adsorption free energy for these types of interactions can be determined from a molecular dynamics simulation using the partitioning between adsorbed and nonadsorbed states, provided that sufficient sampling of both states is obtained. However, if interactions between the solute and the surface are strong, the solute will tend to be trapped near the surface during the simulation, thus preventing the adsorption free energy from being calculated by this method. This situation occurs even when using an advanced sampling algorithm such as replica-exchange molecular dynamics (REMD). In this paper, the authors demonstrate the fundamental basis of this problem using a model system consisting of one sodium ion (Na+) as the solute positioned over a surface functionalized with one negatively charged group (COO−) in explicit water. With this simple system, the authors show that sufficient sampling in the coordinate normal to the surface cannot be obtained by conventional REMD alone. The authors then present a method to overcome this problem through the use of an adaptive windowed-umbrella sampling technique to develop a biased-energy function that is combined with REMD. This approach provides an effective method for the calculation of adsorption free energy for solute-surface interactions. PMID:19768127

  20. Atomic & Molecular Interactions

    SciTech Connect

    2002-07-12

    The Gordon Research Conference (GRC) on Atomic & Molecular Interactions was held at Roger Williams University, Bristol, RI. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  1. Argon Interaction with Gold Surfaces: Ab Initio-Assisted Determination of Pair Ar-Au Potentials for Molecular Dynamics Simulations.

    PubMed

    Grenier, Romain; To, Quy-Dong; de Lara-Castells, María Pilar; Léonard, Céline

    2015-07-01

    Global potentials for the interaction between the Ar atom and gold surfaces are investigated and Ar-Au pair potentials suitable for molecular dynamics simulations are derived. Using a periodic plane-wave representation of the electronic wave function, the nonlocal van-der-Waals vdW-DF2 and vdW-OptB86 approaches have been proved to describe better the interaction. These global interaction potentials have been decomposed to produce pair potentials. Then, the pair potentials have been compared with those derived by combining the dispersionless density functional dlDF for the repulsive part with an effective pairwise dispersion interaction. These repulsive potentials have been obtained from the decomposition of the repulsive interaction between the Ar atom and the Au2 and Au4 clusters and the dispersion coefficients have been evaluated by means of ab initio calculations on the Ar+Au2 complex using symmetry adapted perturbation theory. The pair potentials agree very well with those evaluated through periodic vdW-DF2 calculations. For benchmarking purposes, CCSD(T) calculations have also been performed for the ArAu and Ar+Au2 systems using large basis sets and extrapolations to the complete basis set limit. This work highlights that ab initio calculations using very small surface clusters can be used either as an independent cross-check to compare the performance of state-of-the-art vdW-corrected periodic DFT approaches or, directly, to calculate the pair potentials necessary in further molecular dynamics calculations. PMID:26046588

  2. Interaction potential for aluminum nitride: a molecular dynamics study of mechanical and thermal properties of crystalline and amorphous aluminum nitride

    SciTech Connect

    Vashishta, Priya; Kalia, Rajiv K.; Nakano, Aiichiro; Rino, Jose Pedro

    2011-01-01

    An effective interatomic interaction potential for AlN is proposed. The potential consists of two-body and three-body covalent interactions. The two-body potential includes steric repulsions due to atomic sizes, Coulomb interactions resulting from charge transfer between atoms, charge-induced dipole-interactions due to the electronic polarizability of ions, and induced dipole–dipole (van der Waals) interactions. The covalent characters of the Al–N–Al and N–Al–N bonds are described by the three-body potential. The proposed three-body interaction potential is a modification of the Stillinger–Weber form proposed to describe Si. Using the molecular dynamics method, the interaction potential is used to study structural, elastic, and dynamical properties of crystalline and amorphous states of AlN for several densities and temperatures. The structural energy for wurtzite (2H) structure has the lowest energy, followed zinc-blende and rock-salt (RS) structures. The pressure for the structural transformation from wurtzite-to-RS from the common tangent is found to be 24 GPa. For AlN in the wurtzite phase, our computed elastic constants ( C{sub 11} , C{sub 12} , C{sub 13} , C{sub 33} , C{sub 44} , and C{sub 66} ), melting temperature, vibrational density-of-states, and specific heat agree well with the experiments. Predictions are made for the elastic constant as a function of density for the crystalline and amorphous phase. Structural correlations, such as pair distribution function and neutron and x-ray static structure factors are calculated for the amorphous and liquid state.

  3. QSSPN: dynamic simulation of molecular interaction networks describing gene regulation, signalling and whole-cell metabolism in human cells

    PubMed Central

    Fisher, Ciarán P.; Plant, Nicholas J.; Moore, J. Bernadette; Kierzek, Andrzej M.

    2013-01-01

    Motivation: Dynamic simulation of genome-scale molecular interaction networks will enable the mechanistic prediction of genotype–phenotype relationships. Despite advances in quantitative biology, full parameterization of whole-cell models is not yet possible. Simulation methods capable of using available qualitative data are required to develop dynamic whole-cell models through an iterative process of modelling and experimental validation. Results: We formulate quasi-steady state Petri nets (QSSPN), a novel method integrating Petri nets and constraint-based analysis to predict the feasibility of qualitative dynamic behaviours in qualitative models of gene regulation, signalling and whole-cell metabolism. We present the first dynamic simulations including regulatory mechanisms and a genome-scale metabolic network in human cell, using bile acid homeostasis in human hepatocytes as a case study. QSSPN simulations reproduce experimentally determined qualitative dynamic behaviours and permit mechanistic analysis of genotype–phenotype relationships. Availability and implementation: The model and simulation software implemented in C++ are available in supplementary material and at http://sysbio3.fhms.surrey.ac.uk/qsspn/. Contact: a.kierzek@surrey.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24064420

  4. Isolation and characterisation of sericin antifreeze peptides and molecular dynamics modelling of their ice-binding interaction.

    PubMed

    Wu, Jinhong; Rong, Yuzhi; Wang, Zhengwu; Zhou, Yanfu; Wang, Shaoyun; Zhao, Bo

    2015-05-01

    This study aimed to isolate and characterise a novel sericin antifreeze peptide and investigate its ice-binding molecular mechanism. The thermal hysteresis activity of ice-binding sericin peptides (I-SP) was measured and their activity reached as high as 0.94 °C. A P4 fraction, with high hypothermia protective activity and inhibition activity of ice recrystallisation, was obtained from I-SP, and a purified sericin peptide, named SM-AFP, with the sequence of TTSPTNVSTT and a molecular weight of 1009.50 Da was then isolated from the P4 fraction. Treatment of Lactobacillus delbrueckii Subsp. bulgaricus LB340 LYO with 100 μg/ml synthetic SM-AFP led to 1.4-fold increased survival (p < 0.05). Finally, an SM-AFP/ice binding model was constructed and results of molecular dynamics simulation suggested that the binding of SM-AFP with ice and prevention of ice crystal growth could be attributed to hydrogen bond formation, hydrophobic interaction and non-bond interactions. Sericin peptides could be developed into beneficial cryoprotectants and used in frozen food processing. PMID:25529728

  5. Drug-polymer interactions at water-crystal interfaces and implications for crystallization inhibition: molecular dynamics simulations of amphiphilic block copolymer interactions with tolazamide crystals.

    PubMed

    Gao, Yi; Olsen, Kenneth W

    2015-07-01

    A diblock copolymer, poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA), modulates the crystal growth of tolazamide (TLZ), resulting in a crystal morphology change from needles to plates in aqueous media. To understand this crystal surface drug-polymer interaction, we conducted molecular dynamics simulations on crystal surfaces of TLZ in water containing PEG-b-PLA. A 130-ns simulation of the polymer in a large water box was run before initiating 50 ns simulations with each of the crystal surfaces. The simulations demonstrated differentiated drug-polymer interactions that are consistent with experimental studies. Interaction of PEG-b-PLA with the (001) face occurred more rapidly (≤10 ns) and strongly (total interaction energy of -121.1 kJ/mol/monomer) than that with the (010) face (∼35 ns, -85.4 kJ/mol/monomer). There was little interaction with the (100) face. Hydrophobic and van der Waals (VDW) interactions were the dominant forces, accounting for more than 90% of total interaction energies. It suggests that polymers capable of forming strong hydrophobic and VDW interactions might be more effective in inhibiting crystallization of poorly water-soluble and hydrophobic drugs in aqueous media (such as gastrointestinal fluid) than those with hydrogen-bonding capacities. Such in-depth analysis and understanding facilitate the rational selection of polymers in designing supersaturation-based enabling formulations. PMID:26045147

  6. The Molecular Mechanism of Bisphenol A (BPA) as an Endocrine Disruptor by Interacting with Nuclear Receptors: Insights from Molecular Dynamics (MD) Simulations

    PubMed Central

    Li, Lanlan; Wang, Qianqian; Zhang, Yan; Niu, Yuzhen; Yao, Xiaojun; Liu, Huanxiang

    2015-01-01

    Bisphenol A (BPA) can interact with nuclear receptors and affect the normal function of nuclear receptors in very low doses, which causes BPA to be one of the most controversial endocrine disruptors. However, the detailed molecular mechanism about how BPA interferes the normal function of nuclear receptors is still undiscovered. Herein, molecular dynamics simulations were performed to explore the detailed interaction mechanism between BPA with three typical nuclear receptors, including hERα, hERRγ and hPPARγ. The simulation results and calculated binding free energies indicate that BPA can bind to these three nuclear receptors. The binding affinities of BPA were slightly lower than that of E2 to these three receptors. The simulation results proved that the binding process was mainly driven by direct hydrogen bond and hydrophobic interactions. In addition, structural analysis suggested that BPA could interact with these nuclear receptors by mimicking the action of natural hormone and keeping the nuclear receptors in active conformations. The present work provided the structural evidence to recognize BPA as an endocrine disruptor and would be important guidance for seeking safer substitutions of BPA. PMID:25799048

  7. Interactions of the SAP Domain of Human Ku70 with DNA Substrate: A Molecular Dynamics Study

    NASA Technical Reports Server (NTRS)

    Hu, Shaowen; Carra, Claudio; Huff, Janice; Pluth, Janice M.; Cucinotta, Francis A.

    2007-01-01

    NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku70/80 complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The SAP domain of Ku70 (residues 556-609), contains an a helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the SAP/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the SAP domain of Ku70 and a 10 base pairs DNA duplex. Large-scale conformational changes were observed and some putative binding modes were suggested based on energetic analysis. These modes are consistent with previous experimental investigations. In addition, the results indicate that cooperation of SAP with other domains of Ku70/80 is necessary to explain the high affinity of binding as observed in experiments.

  8. Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3-3 Protein-Protein Interactions.

    PubMed

    Cau, Ylenia; Fiorillo, Annarita; Mori, Mattia; Ilari, Andrea; Botta, Maurizo; Lalle, Marco

    2015-12-28

    Giardiasis is a gastrointestinal diarrheal illness caused by the protozoan parasite Giardia duodenalis, which affects annually over 200 million people worldwide. The limited antigiardial drug arsenal and the emergence of clinical cases refractory to standard treatments dictate the need for new chemotherapeutics. The 14-3-3 family of regulatory proteins, extensively involved in protein-protein interactions (PPIs) with pSer/pThr clients, represents a highly promising target. Despite homology with human counterparts, the single 14-3-3 of G. duodenalis (g14-3-3) is characterized by a constitutive phosphorylation in a region critical for target binding, thus affecting the function and the conformation of g14-3-3/clients interaction. However, to approach the design of specific small molecule modulators of g14-3-3 PPIs, structural elucidations are required. Here, we present a detailed computational and crystallographic study exploring the implications of g14-3-3 phosphorylation on protein structure and target binding. Self-Guided Langevin Dynamics and classical molecular dynamics simulations show that phosphorylation affects locally and globally g14-3-3 conformation, inducing a structural rearrangement more suitable for target binding. Profitable features for g14-3-3/clients interaction were highlighted using a hydrophobicity-based descriptor to characterize g14-3-3 client peptides. Finally, the X-ray structure of g14-3-3 in complex with a mode-1 prototype phosphopeptide was solved and combined with structure-based simulations to identify molecular features relevant for clients binding to g14-3-3. The data presented herein provide a further and structural understanding of g14-3-3 features and set the basis for drug design studies. PMID:26551337

  9. Nonequilibrium molecular dynamics

    SciTech Connect

    Hoover, W.G. . Dept. of Applied Science Lawrence Livermore National Lab., CA )

    1990-11-01

    The development of nonequilibrium molecular dynamics is described, with emphasis on massively-parallel simulations involving the motion of millions, soon to be billions, of atoms. Corresponding continuum simulations are also discussed. 14 refs., 8 figs.

  10. Effects of cholesterol concentration on the interaction of cytarabine with lipid membranes: a molecular dynamics simulation study.

    PubMed

    Karami, Leila; Jalili, Seifollah

    2015-01-01

    Liposomal cytarabine, DepoCyt, is a chemotherapy agent which is used in cancer treatment. This form of cytarabine has more efficacy and fewer side effects relative to the other forms. Since DepoCyt contains the cytarabine encapsulated within phosphatidylcholine and the sterol molecules, we modeled dioleoylphosphatidylcholine (DOPC)/cholesterol bilayer membrane as a carrier for cytarabine to study drug-bilayer interactions. For this purpose, we performed a series of united-atom molecular dynamics (MD) simulations for 25 ns to investigate the interactions between cytarabine and cholesterol-containing DOPC lipid bilayers. Only the uncharged form of cytarabine molecule was investigated. In this study, different levels of the cholesterol content (0, 20, and 40%) were used. MD simulations allowed us to determine dynamical and structural properties of the bilayer membrane and to estimate the preferred location and orientation of the cytarabine molecule inside the bilayer membrane. Properties such as membrane thickness, area per lipid, diffusion coefficient, mass density, bilayer packing, order parameters, and intermolecular interactions were examined. The results show that by increasing the cholesterol concentration in the lipid bilayers, the bilayer thickness increases and area per lipid decreases. Moreover, in accordance with the experiments, our calculations show that cholesterol molecules have ordering effect on the hydrocarbon acyl chains. Furthermore, the cytarabine molecule preferentially occupies the polar region of the lipid head groups to form specific interactions (hydrogen bonds). Our results fully support the experimental data. Our finding about drug-bilayer interaction is crucial for the liposomal drug design. PMID:25068451

  11. Visualizing Protein Interactions and Dynamics: Evolving a Visual Language for Molecular Animation

    ERIC Educational Resources Information Center

    Jenkinson, Jodie; McGill, Gael

    2012-01-01

    Undergraduate biology education provides students with a number of learning challenges. Subject areas that are particularly difficult to understand include protein conformational change and stability, diffusion and random molecular motion, and molecular crowding. In this study, we examined the relative effectiveness of three-dimensional…

  12. Comprehensive molecular dynamics simulations of the stacking fault tetrahedron interacting with a mixed dislocation at elevated temperature

    NASA Astrophysics Data System (ADS)

    Fan, Haidong; Wang, Qingyuan; Ouyang, Chaojun

    2015-10-01

    The defect-free channels were frequently observed in irradiated materials, i.e. copper, as a result of the stacking fault tetrahedron (SFT) interactions with dislocations. However, the underlying mechanisms for this process are still unclear to date. To address them, a comprehensive study on the interactions between SFTs and mixed dislocations was performed using molecular dynamics simulations. In particular, eight interaction geometries were considered, in terms of the dislocation Burgers vector directions, dislocation gliding directions and intersection positions on SFT. Various interaction outcomes were revealed after dislocation detachment. (1) SFT is fully absorbed through the transformation into Lomer dislocations, and subsequently moves out of free surfaces along the dislocation. (2) SFT is partially absorbed with the absorbed SFT base moving out of free surfaces along the dislocation. (3) SFT is not absorbed but sheared with ledges left on the SFT faces. (4) SFT is unaffected by the mixed dislocation. The current simulations, especially the full SFT absorption, provide important insights into the forming mechanisms of defect-free channels in irradiated materials.

  13. 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. PMID:26657340

  14. MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures

    PubMed Central

    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

    2015-01-01

    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. PMID:26657340

  15. VMD: visual molecular dynamics.

    PubMed

    Humphrey, W; Dalke, A; Schulten, K

    1996-02-01

    VMD is a molecular graphics program designed for the display and analysis of molecular assemblies, in particular biopolymers such as proteins and nucleic acids. VMD can simultaneously display any number of structures using a wide variety of rendering styles and coloring methods. Molecules are displayed as one or more "representations," in which each representation embodies a particular rendering method and coloring scheme for a selected subset of atoms. The atoms displayed in each representation are chosen using an extensive atom selection syntax, which includes Boolean operators and regular expressions. VMD provides a complete graphical user interface for program control, as well as a text interface using the Tcl embeddable parser to allow for complex scripts with variable substitution, control loops, and function calls. Full session logging is supported, which produces a VMD command script for later playback. High-resolution raster images of displayed molecules may be produced by generating input scripts for use by a number of photorealistic image-rendering applications. VMD has also been expressly designed with the ability to animate molecular dynamics (MD) simulation trajectories, imported either from files or from a direct connection to a running MD simulation. VMD is the visualization component of MDScope, a set of tools for interactive problem solving in structural biology, which also includes the parallel MD program NAMD, and the MDCOMM software used to connect the visualization and simulation programs. VMD is written in C++, using an object-oriented design; the program, including source code and extensive documentation, is freely available via anonymous ftp and through the World Wide Web. PMID:8744570

  16. Glycosylation Effects on FSH-FSHR Interaction Dynamics: A Case Study of Different FSH Glycoforms by Molecular Dynamics Simulations

    PubMed Central

    Meher, Biswa Ranjan; Dixit, Anshuman; Bousfield, George R.; Lushington, Gerald H.

    2015-01-01

    The gonadotropin known as follicle-stimulating hormone (FSH) plays a key role in regulating reproductive processes. Physiologically active FSH is a glycoprotein that can accommodate glycans on up to four asparagine residues, including two sites in the FSHα subunit that are critical for biochemical function, plus two sites in the β subunit, whose differential glycosylation states appear to correspond to physiologically distinct functions. Some degree of FSHβ hypo-glycosylation seems to confer advantages toward reproductive fertility of child-bearing females. In order to identify possible mechanistic underpinnings for this physiological difference we have pursued computationally intensive molecular dynamics simulations on complexes between the high affinity site of the gonadal FSH receptor (FSHR) and several FSH glycoforms including fully-glycosylated (FSH24), hypo-glycosylated (e.g., FSH15), and completely deglycosylated FSH (dgFSH). These simulations suggest that deviations in FSH/FSHR binding profile as a function of glycosylation state are modest when FSH is adorned with only small glycans, such as single N-acetylglucosamine residues. However, substantial qualitative differences emerge between FSH15 and FSH24 when FSH is decorated with a much larger, tetra-antennary glycan. Specifically, the FSHR complex with hypo-glycosylated FSH15 is observed to undergo a significant conformational shift after 5–10 ns of simulation, indicating that FSH15 has greater conformational flexibility than FSH24 which may explain the more favorable FSH15 kinetic profile. FSH15 also exhibits a stronger binding free energy, due in large part to formation of closer and more persistent salt-bridges with FSHR. PMID:26402790

  17. Protein-Mineral Interactions: Molecular Dynamics Simulations Capture Importance of Variations in Mineral Surface Composition and Structure.

    PubMed

    Andersen, Amity; Reardon, Patrick N; Chacon, Stephany S; Qafoku, Nikolla P; Washton, Nancy M; Kleber, Markus

    2016-06-21

    Molecular dynamics simulations, conventional and metadynamics, were performed to determine the interaction of model protein Gb1 over kaolinite (001), Na(+)-montmorillonite (001), Ca(2+)-montmorillonite (001), goethite (100), and Na(+)-birnessite (001) mineral surfaces. Gb1, a small (56 residue) protein with a well-characterized solution-state nuclear magnetic resonance (NMR) structure and having α-helix, 4-fold β-sheet, and hydrophobic core features, is used as a model protein to study protein soil mineral interactions and gain insights on structural changes and potential degradation of protein. From our simulations, we observe little change to the hydrated Gb1 structure over the kaolinite, montmorillonite, and goethite surfaces relative to its solvated structure without these mineral surfaces present. Over the Na(+)-birnessite basal surface, however, the Gb1 structure is highly disturbed as a result of interaction with this birnessite surface. Unraveling of the Gb1 β-sheet at specific turns and a partial unraveling of the α-helix is observed over birnessite, which suggests specific vulnerable residue sites for oxidation or hydrolysis possibly leading to fragmentation. PMID:27243116

  18. Investigation of allosteric modulation mechanism of metabotropic glutamate receptor 1 by molecular dynamics simulations, free energy and weak interaction analysis

    PubMed Central

    Bai, Qifeng; Yao, Xiaojun

    2016-01-01

    Metabotropic glutamate receptor 1 (mGlu1), which belongs to class C G protein-coupled receptors (GPCRs), can be coupled with G protein to transfer extracellular signal by dimerization and allosteric regulation. Unraveling the dimer packing and allosteric mechanism can be of great help for understanding specific regulatory mechanism and designing more potential negative allosteric modulator (NAM). Here, we report molecular dynamics simulation studies of the modulation mechanism of FITM on the wild type, T815M and Y805A mutants of mGlu1 through weak interaction analysis and free energy calculation. The weak interaction analysis demonstrates that van der Waals (vdW) and hydrogen bonding play an important role on the dimer packing between six cholesterol molecules and mGlu1 as well as the interaction between allosteric sites T815, Y805 and FITM in wild type, T815M and Y805A mutants of mGlu1. Besides, the results of free energy calculations indicate that secondary binding pocket is mainly formed by the residues Thr748, Cys746, Lys811 and Ser735 except for FITM-bound pocket in crystal structure. Our results can not only reveal the dimer packing and allosteric regulation mechanism, but also can supply useful information for the design of potential NAM of mGlu1. PMID:26887338

  19. Interaction of collagen with chlorosulphonated paraffin tanning agents: Fourier transform infrared spectroscopic analysis and molecular dynamics simulations.

    PubMed

    Monti, Susanna; Bramanti, Emilia; Della Porta, Valentina; Onor, Massimo; D'Ulivo, Alessandro; Barone, Vincenzo

    2013-09-21

    The binding of chlorosulphonated paraffins to collagen triple helices is studied by means of classical molecular dynamics simulations and experimental spectroscopic techniques in order to disclose the principal characteristics of their interaction during the leather fattening process. Indeed, collagen is the main target to develop new leather modifying agents with specific characteristics, and an accurate design of the collagen binders, supported by predictive computational strategies, could be a successful tool to obtain new effective eco-compatible compounds able to impart to the leather the required functionalities and distinctive mechanical properties. Possible effects caused by the tanning agents on the collagen matrix have been identified from both experimental and theoretical points of view. Computational data in agreement with experiment have revealed that chlorosulphonated paraffins can interact favorably with the collagen residues having amine groups in their side chains (Arg, Lys, Asn and Gln) and reduce the tendency of the solvated collagen matrix to swell. However, the interference of chlorosulphonated paraffins with the unfolding process, which is operated mainly by the action of water, can be due both to covalent cross-linking of the collagen chains and intermolecular hydrogen bonding interactions involving also the hydroxyl groups of Hyp, Ser and Thr residues. PMID:23904010

  20. Investigation of allosteric modulation mechanism of metabotropic glutamate receptor 1 by molecular dynamics simulations, free energy and weak interaction analysis

    NASA Astrophysics Data System (ADS)

    Bai, Qifeng; Yao, Xiaojun

    2016-02-01

    Metabotropic glutamate receptor 1 (mGlu1), which belongs to class C G protein-coupled receptors (GPCRs), can be coupled with G protein to transfer extracellular signal by dimerization and allosteric regulation. Unraveling the dimer packing and allosteric mechanism can be of great help for understanding specific regulatory mechanism and designing more potential negative allosteric modulator (NAM). Here, we report molecular dynamics simulation studies of the modulation mechanism of FITM on the wild type, T815M and Y805A mutants of mGlu1 through weak interaction analysis and free energy calculation. The weak interaction analysis demonstrates that van der Waals (vdW) and hydrogen bonding play an important role on the dimer packing between six cholesterol molecules and mGlu1 as well as the interaction between allosteric sites T815, Y805 and FITM in wild type, T815M and Y805A mutants of mGlu1. Besides, the results of free energy calculations indicate that secondary binding pocket is mainly formed by the residues Thr748, Cys746, Lys811 and Ser735 except for FITM-bound pocket in crystal structure. Our results can not only reveal the dimer packing and allosteric regulation mechanism, but also can supply useful information for the design of potential NAM of mGlu1.

  1. Interactions of the designed antimicrobial peptide MB21 and truncated dermaseptin S3 with lipid bilayers: molecular-dynamics simulations.

    PubMed Central

    Shepherd, Craig M; Vogel, Hans J; Tieleman, D Peter

    2003-01-01

    Molecular-dynamics simulations covering 30 ns of both a natural and a synthetic antimicrobial peptide in the presence of a zwitterionic lipid bilayer were performed. In both simulations, copies of the peptides were placed in an alpha-helical conformation on either side of the bilayer about 10 A (1 A=0.1 nm) from the interface, with either the hydrophobic or the positively charged face of the helix directed toward the bilayer surface. The degree of peptide-lipid interaction was dependent on the starting configuration: surface binding and subsequent penetration of the bilayer was observed for the hydrophobically oriented peptides, while the charge-oriented peptides demonstrated at most partial surface binding. Aromatic residues near the N-termini of the peptides appear to play an important role in driving peptide-lipid interactions. A correlation between the extent of peptide-lipid interactions and helical stability was observed in the simulations. Insertion of the peptides into the bilayer caused a dramatic increase in the lateral area per lipid and decrease in the bilayer thickness, resulting in substantial disordering of the lipid chains. Results from the simulations are consistent with early stages of proposed mechanisms for the lytic activity of antimicrobial peptides. In addition to these 'free' simulations, 25 ns simulations were carried out with the peptides constrained at three different distances relative to the bilayer interface. The constraint forces are in agreement with the extent of peptide-bilayer insertion observed in the free simulations. PMID:12423203

  2. 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.

  3. Interaction of the Antimicrobial Peptide Polymyxin B1 with Both Membranes of E. coli: A Molecular Dynamics Study

    PubMed Central

    Jefferies, Damien; Sessions, Richard B.; Bond, Peter J.; Khalid, Syma

    2015-01-01

    Antimicrobial peptides are small, cationic proteins that can induce lysis of bacterial cells through interaction with their membranes. Different mechanisms for cell lysis have been proposed, but these models tend to neglect the role of the chemical composition of the membrane, which differs between bacterial species and can be heterogeneous even within a single cell. Moreover, the cell envelope of Gram-negative bacteria such as E. coli contains two membranes with differing compositions. To this end, we report the first molecular dynamics simulation study of the interaction of the antimicrobial peptide, polymyxin B1 with complex models of both the inner and outer membranes of E. coli. The results of >16 microseconds of simulation predict that polymyxin B1 is likely to interact with the membranes via distinct mechanisms. The lipopeptides aggregate in the lipopolysaccharide headgroup region of the outer membrane with limited tendency for insertion within the lipid A tails. In contrast, the lipopeptides readily insert into the inner membrane core, and the concomitant increased hydration may be responsible for bilayer destabilization and antimicrobial function. Given the urgent need to develop novel, potent antibiotics, the results presented here reveal key mechanistic details that may be exploited for future rational drug development. PMID:25885324

  4. Energy and structure of bonds in the interaction of organic anions with layered double hydroxide nanosheets: A molecular dynamics study.

    PubMed

    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. PMID:26817816

  5. Energy and structure of bonds in the interaction of organic anions with layered double hydroxide nanosheets: A molecular dynamics study

    PubMed Central

    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. PMID:26817816

  6. Molecular Dynamics of Water Mediated Interactions of a Linear Benzimidazole-Biphenyl Diamidine with the DNA Minor Groove

    PubMed Central

    Athri, Prashanth; Wilson, W. David

    2009-01-01

    DB921 has a benzimidazole-biphenyl system with terminal amidines that gives the compound a linear conformation with a radius of curvature that does not match the DNA minor groove shape. Surprisingly, the compound binds in the groove with an unusually high equilibrium constant [Miao, Y.; Lee, M. P. H.; Parkinson, G. N.; Batista-Parra, A.; Ismail, M. A.; Neidle, S.; Boykin, D. W.; Wilson, W. D. Biochemistry 2005, 44, 14701-14708]. X-ray crystallographic analysis of DB921 bound to -AATT- in d(CGCGAATTCGCG)2 showed that the benzimidazole is in position to directly interact with bases at the floor of the groove while the phenylamidine of DB921 forms indirect contacts with the bases through an interfacial water. The DB921-water pair forms a curved, flexible module with a high Ka (or a low Kd) value of binding. To better understand the dynamics of the DB921-DNA complex and how water can be used in the design of compounds to recognize DNA, a 100 ns molecular dynamics simulation of the complex was conducted. In addition to the X-ray conformation some significantly variant, dynamic conformations, which had additional interfacial water molecules between DB921 and DNA, appeared in the MD simulation. The benzimidazole contacts remained relatively constant through the entire simulation. The biphenyl-amidine end of the bound molecule, however, undergoes much larger changes in orientation relative to the floor of the groove as well as variations in the type of water interactions. The results provide an understanding of how water couples the linear DB921 compound to the minor groove for tight binding, without a large unfavorable contribution to the entropy of binding. PMID:19445463

  7. Interaction of polar and nonpolar organic pollutants with soil organic matter: sorption experiments and molecular dynamics simulation.

    PubMed

    Ahmed, Ashour A; Thiele-Bruhn, Sören; Aziz, Saadullah G; Hilal, Rifaat H; Elroby, Shaaban A; Al-Youbi, Abdulrahman O; Leinweber, Peter; Kühn, Oliver

    2015-03-01

    The fate of organic pollutants in the environment is influenced by several factors including the type and strength of their interactions with soil components especially SOM. However, a molecular level answer to the question "How organic pollutants interact with SOM?" is still lacking. In order to explore mechanisms of this interaction, we have developed a new SOM model and carried out molecular dynamics (MD) simulations in parallel with sorption experiments. The new SOM model comprises free SOM functional groups (carboxylic acid and naphthalene) as well as SOM cavities (with two different sizes), simulating the soil voids, containing the same SOM functional groups. To examine the effect of the hydrophobicity on the interaction, the organic pollutants hexachlorobenzene (HCB, non-polar) and sulfanilamide (SAA, polar) were considered. The experimental and theoretical investigations explored four major points regarding sorption of SAA and HCB on soil, yielding the following results. 1--The interaction depends on the SOM chemical composition more than the SOM content. 2--The interaction causes a site-specific adsorption on the soil surfaces. 3--Sorption hysteresis occurs, which can be explained by inclusion of these pollutants inside soil voids. 4--The hydrophobic HCB is adsorbed on soil stronger than the hydrophilic SAA. Moreover, the theoretical results showed that HCB forms stable complexes with all SOM models in the aqueous solution, while most of SAA-SOM complexes are accompanied by dissociation into SAA and the free SOM models. The SOM-cavity modeling had a significant effect on binding of organic pollutants to SOM. Both HCB and SAA bind to the SOM models in the order of models with a small cavity>a large cavity>no cavity. Although HCB binds to all SOM models stronger than SAA, the latter is more affected by the presence of the cavity. Finally, HCB and SAA bind to the hydrophobic functional group (naphthalene) stronger than to the hydrophilic one (carboxylic acid

  8. Molecular dynamics simulations of the interactions of DMSO, mono- and polyhydroxylated cryosolvents with a hydrated phospholipid bilayer.

    PubMed

    Malajczuk, Chris J; Hughes, Zak E; Mancera, Ricardo L

    2013-09-01

    Molecular dynamics (MD) simulations have been used to investigate the interactions of a variety of hydroxylated cryosolvents (glycerol, propylene glycol and ethylene glycol), methanol and dimethyl sulfoxide (DMSO) in aqueous solution with a 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayer in its fluid phase at 323K. Each cryosolvent induced lateral expansion of the membrane leading to thinning of the bilayer and resulting in disordering of the lipid hydrocarbon chains. Propylene glycol and DMSO were observed to exhibit a greater disordering effect on the structure of the membrane than the other three alcohols. Closer examination exposed a number of effects on the lipid bilayer as a function of the molecular size and hydrogen bonding capacity of the cryosolvents. Analyses of hydrogen bonds revealed that increased concentrations of the polyhydroxylated cryosolvents induced the formation of a cross-linked cryosolvent layer across the surface of the membrane bilayer. This effect was most pronounced for glycerol at sufficiently high concentrations, which displayed a comparatively enhanced capacity to induce cross-linking of lipid headgroups resulting in the formation of extensive hydrogen bonding bridges and the promotion of a dense cryosolvent layer across the phospholipid bilayer. PMID:23707690

  9. A microfluidic chamber to study the dynamics of muscle-contraction-specific molecular interactions.

    PubMed

    Roman, Horia Nicolae; Juncker, David; Lauzon, Anne-Marie

    2015-03-01

    In vitro motility and laser trap assays are commonly used for molecular mechanics measurements. However, chemicals cannot be added during these measurements, because they create flows that alter the molecular mechanics. Thus, we designed a microfluidic device that allows the addition of chemicals without creating bulk flows. Biocompatibility of the components of this device was tested. A microchannel chamber was created by photolithography with the patterns transferred to polydimethylsiloxane (PDMS). The PDMS chamber was bound to a polycarbonate membrane, which itself was bound to a molecular mechanics chamber. The microchannels ensured rapid distribution of the chemicals over the membrane, whereas the membrane ensured efficient delivery to the mechanics chamber while preventing bulk flow. The biocompatibility of the materials was tested by comparing the velocity (ν(max)) of propulsion by myosin of fluorescently labeled actin filaments to that of the conventional assay; no difference in ν(max) was observed. To estimate total chemical delivery time, labeled bovine serum albumin was injected in the channel chamber and TIRF was used to determine the time to reach the assay surface (2.7 ± 0.1 s). Furthermore, the standard distance of a trapped microsphere calculated during buffer diffusion using the microfluidic device (14.9 ± 3.2 nm) was not different from that calculated using the conventional assay (15.6 ± 5.3 nm, p = 0.922). Finally, ν(max) obtained by injecting adenosine triphosphate (ATP) in the microchannel chamber (2.37 ± 0.48 μm/s) was not different from that obtained when ATP was delivered directly to the mechanics chamber (2.52 ± 0.42 μm/s, p = 0.822). This microfluidic prototype validates the design for molecular mechanics measurements. PMID:25629255

  10. The Interaction Potential of an Open Nanotube and its Permeability: Molecular Dynamics Simulation

    NASA Astrophysics Data System (ADS)

    Bubenchikov, Mikhail A.; Potekaev, Alexander I.; Bubenchikov, Alexey M.; Usenko, Olesya V.; Malozemov, Alexander V.; Tarasov, Egor A.

    2016-02-01

    The integration of the modified LJ-potential allowed revealing the universal effect of the open carbon tube on the molecular objects moving within or proximate to the tube. There has been established that there are modes of the molecule motion without the energy exchange with the atoms of the carbon framing, under which the moving molecules are subjected to the considerable activation in the tube. The potential holes being the sorption zones in fact are localized.

  11. Substructured multibody molecular dynamics.

    SciTech Connect

    Grest, Gary Stephen; Stevens, Mark Jackson; Plimpton, Steven James; Woolf, Thomas B. (Johns Hopkins University, Baltimore, MD); Lehoucq, Richard B.; Crozier, Paul Stewart; Ismail, Ahmed E.; Mukherjee, Rudranarayan M. (Rensselaer Polytechnic Institute, Troy, NY); Draganescu, Andrei I.

    2006-11-01

    We have enhanced our parallel molecular dynamics (MD) simulation software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator, lammps.sandia.gov) to include many new features for accelerated simulation including articulated rigid body dynamics via coupling to the Rensselaer Polytechnic Institute code POEMS (Parallelizable Open-source Efficient Multibody Software). We use new features of the LAMMPS software package to investigate rhodopsin photoisomerization, and water model surface tension and capillary waves at the vapor-liquid interface. Finally, we motivate the recipes of MD for practitioners and researchers in numerical analysis and computational mechanics.

  12. Superposition State Molecular Dynamics.

    PubMed

    Venkatnathan, Arun; Voth, Gregory A

    2005-01-01

    The ergodic sampling of rough energy landscapes is crucial for understanding phenomena like protein folding, peptide aggregation, polymer dynamics, and the glass transition. These rough energy landscapes are characterized by the presence of many local minima separated by high energy barriers, where Molecular Dynamics (MD) fails to satisfy ergodicity. To enhance ergodic behavior, we have developed the Superposition State Molecular Dynamics (SSMD) method, which uses a superposition of energy states to obtain an effective potential for the MD simulation. In turn, the dynamics on this effective potential can be used to sample the configurational free energy of the real potential. The effectiveness of the SSMD method for a one-dimensional rough potential energy landscape is presented as a test case. PMID:26641113

  13. Factors affecting the interactions between beta-lactoglobulin and fatty acids as revealed in molecular dynamics simulations.

    PubMed

    Yi, Changhong; Wambo, Thierry O

    2015-09-21

    Beta-lactoglobulin (BLG), a bovine dairy protein, is a promiscuously interacting protein that can bind multiple hydrophobic ligands. Fatty acids (FAs), common hydrophobic molecules bound to BLG, are important sources of fuel for life because they yield large quantities of ATP when metabolized. The binding affinity increases with the length of the ligands, indicating the importance of the van der Waals (vdW) interactions between the hydrocarbon tail and the hydrophobic calyx of BLG. An exception to this rule is caprylic acid (OCA) which is two-carbon shorter but has a stronger binding affinity than capric acid. Theoretical calculations in the current literature are not accurate enough to shed light on the underlying physics of this exception. The computed affinity values are greater for longer fatty acids without respect for the caprylic exception and those values are generally several orders of magnitude away from the experimental data. In this work, we used hybrid steered molecular dynamics to accurately compute the binding free energies between BLG and the five saturated FAs of 8 to 16 carbon atoms. The computed binding free energies agree well with experimental data not only in rank but also in absolute values. We gained insights into the exceptional behavior of caprylic acid in the computed values of entropy and electrostatic interactions. We found that the electrostatic interaction between the carboxyl group of caprylic acid and the two amino groups of K60/69 in BLG is much stronger than the vdW force between the OCA's hydrophobic tail and the BLG calyx. This pulls OCA to the top of the beta barrel where it is easier to fluctuate, giving rise to greater entropy of OCA at the binding site. PMID:26272099

  14. A molecular dynamics study of the hydroxyl radical in solution applying self-interaction-corrected density functional methods.

    PubMed

    VandeVondele, Joost; Sprik, Michiel

    2005-04-01

    We have performed density functional theory based molecular dynamics (MD) simulations of the *OH radical in solution using self-interaction corrected (SIC) methods. We use a scheme recently proposed by M. d'Avezac, M. Calandra and F. Mauri [arXiv:cond-mat/0407750] in which a correction is only applied to the spin density within a restricted open shell formulation. In addition to two correction formulas employed within this scheme by M. d'Avezac, M. Calandra and F. Mauri, we propose and test an new empirical form which only introduces a scaled Coulomb term. This new functional leads to good agreement with reference calculations on radical cation dimers and on the hydroxyl water dimer in the gas phase. Applied in ab initio MD simulations, these three SIC methods provide a picture of the *OH solvation that differs qualitatively from the one obtained using the standard generalised gradient approximation (GGA). Hemibonded water, observed in GGA simulations and believed to be an artefact due to self-interaction error, is not present. We find that the *OH acts as a good hydrogen bond donor, but accepts less than two hydrogen bonds on average. These hydrogen bonds are part of a mobile, otherwise quasi-hydrophobic solvation cage. Our results show the potential of this computationally expedient scheme, which might extend the range of problems that can be modelled adequately with density functional theory. PMID:19787955

  15. Similarities and differences of serotonin and its precursors in their interactions with model membranes studied by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Wood, Irene; Martini, M. Florencia; Pickholz, Mónica

    2013-08-01

    In this work, we report a molecular dynamics (MD) simulations study of relevant biological molecules as serotonin (neutral and protonated) and its precursors, tryptophan and 5-hydroxy-tryptophan, in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC). The simulations were carried out at the fluid lamellar phase of POPC at constant pressure and temperature conditions. Two guest molecules of each type were initially placed at the water phase. We have analyzed, the main localization, preferential orientation and specific interactions of the guest molecules within the bilayer. During the simulation run, the four molecules were preferentially found at the water-lipid interphase. We found that the interactions that stabilized the systems are essentially hydrogen bonds, salt bridges and cation-π. None of the guest molecules have access to the hydrophobic region of the bilayer. Besides, zwitterionic molecules have access to the water phase, while protonated serotonin is anchored in the interphase. Even taking into account that these simulations were done using a model membrane, our results suggest that the studied molecules could not cross the blood brain barrier by diffusion. These results are in good agreement with works that show that serotonin and Trp do not cross the BBB by simple diffusion.

  16. Molecular dynamics study on the interactions between helium projectiles and helium bubbles pre-existing in tungsten surfaces

    NASA Astrophysics Data System (ADS)

    Ding, Yuan; Ma, Chaoqiong; Li, Min; Hou, Qing

    2016-02-01

    Molecular dynamics simulations were performed to study the interactions between low-energy (⩽100 eV) helium (He) projectiles and helium bubbles pre-existing near tungsten (W) surfaces. It is observed that with increasing bubble size, the reflection coefficient of the He projectiles was reduced, and the channelling effect that could be observed with no pre-existing He bubble was depressed. The He projectiles can be captured by pre-existing He bubbles and also knock He atoms out of the bubbles. The spatial distribution of the single He atoms, including both the slowed-down projectiles and the knocked-out He atoms, was extracted. The single He atoms were found distributed around the bubbles in a region with the width of 3-5.5 in lattice lengths of W. Although the results were obtained for the interaction of He projectiles with isolated He bubbles pre-existing in W, they suggest that the reflection and retention status of He projectiles would change during the irradiation of high flux/fluence He on W surfaces due to the change of He bubbles coverage near W surfaces. The results can be coupled with Monte Carlo modelling in conditions closer to that in experiments of high flux/fluence He bombardments on W surfaces.

  17. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase

    PubMed Central

    Sharma, Reetu; Sastry, G. Narahari

    2015-01-01

    Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant’s functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies. PMID:26657745

  18. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

    PubMed

    Sharma, Reetu; Sastry, G Narahari

    2015-01-01

    Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies. PMID:26657745

  19. Environmental Changes in MoTe2 Excitonic Dynamics by Defects-Activated Molecular Interaction.

    PubMed

    Chen, Bin; Sahin, Hasan; Suslu, Aslihan; Ding, Laura; Bertoni, Mariana I; Peeters, F M; Tongay, Sefaattin

    2015-05-26

    Monolayers of group VI transition metal dichalcogenides possess direct gaps in the visible spectrum with the exception of MoTe2, where its gap is suitably located in the infrared region but its stability is of particular interest, as tellurium compounds are acutely sensitive to oxygen exposure. Here, our environmental (time-dependent) measurements reveal two distinct effects on MoTe2 monolayers: For weakly luminescent monolayers, photoluminescence signal and optical contrast disappear, as if they are decomposed, but yet remain intact as evidenced by AFM and Raman measurements. In contrast, strongly luminescent monolayers retain their optical contrast for a prolonged amount of time, while their PL peak blue-shifts and PL intensity saturates to slightly lower values. Our X-ray photoelectron spectroscopy measurements and DFT calculations suggest that the presence of defects and functionalization of these defect sites with O2 molecules strongly dictate their material properties and aging response by changing the excitonic dynamics due to deep or shallow states that are created within the optical band gap. Presented results not only shed light on environmental effects on fundamental material properties and excitonic dynamics of MoTe2 monolayers but also highlight striking material transformation for metastable 2D systems such as WTe2, silicone, and phosphorene. PMID:25868985

  20. Structures of [Li(glyme)](+) complexes and their interactions with anions in equimolar mixtures of glymes and Li[TFSA]: analysis by molecular dynamics simulations.

    PubMed

    Tsuzuki, Seiji; Shinoda, Wataru; Matsugami, Masaru; Umebayashi, Yasuhiro; Ueno, Kazuhide; Mandai, Toshihiko; Seki, Shiro; Dokko, Kaoru; Watanabe, Masayoshi

    2015-01-01

    Molecular dynamics simulations of equimolar mixtures of glymes (triglyme and tetraglyme) and Li[TFSA] (lithium bis(trifluoromethylsulfonyl)amide) show that the glyme chain length affects the coordination geometries of Li(+), which induces the changes in interactions between the [Li(glyme)](+) complex and [TFSA](-) anions and diffusion of ions in the equimolar mixtures. PMID:25407234

  1. The distal residue-CO interaction in carbonmonoxy myoglobins: a molecular dynamics study of two distal histidine tautomers.

    PubMed Central

    Jewsbury, P; Kitagawa, T

    1994-01-01

    Four independent 90 ps molecular dynamics simulations of sperm-whale wild-type carbonmonoxy myoglobin (MbCO) have been calculated using a new AMBER force field for the haem prosthetic group. Two trajectories have the distal 64N delta nitrogen protonated, and two have the 64N epsilon nitrogen protonated; all water molecules within 16 A of the carbonyl O are included. In three trajectories, the distal residue remains part of the haem pocket, with the protonated distal nitrogen pointing into the active site. This is in contrast with the neutron diffraction crystal structure, but is consistent with the solution phase CO stretching frequencies (upsilon CO) of MbCO and various of its mutants. There are significant differences in the "closed" pocket structures found for each tautomer: the 64N epsilon H trajectories both show stable distal-CO interactions, whereas the 64N delta H tautomer) has a weaker interaction resulting in a more mobile distal side chain. One trajectory (a 64N delta H tautomer) has the distal histidine moving out into the "solvent", leaving the pocket in an "open" structure, with a large unhindered entrance to the active site. These trajectories suggest that the three upsilon CO frequencies observed for wild-type MbCO in solution, rather than representing significantly different Fe-C-O geometries as such, arise from three different haem pocket structures, each with different electric fields at the ligand. Each pocket structure corresponds to a different distal histidine conformer: the A3 band to the 64N epsilon H tautomer, the A1,2 band to the 64N delta H tautomer, and the A0 band to the absence of any significant interaction with the distal side chain. PMID:7696465

  2. Interaction between water molecules and zinc sulfide nanoparticles studied by temperature-programmed desorption and molecular dynamics simulations.

    PubMed

    Zhang, Hengzhong; Rustad, James R; Banfield, Jillian F

    2007-06-14

    We have investigated the bonding of water molecules to the surfaces of ZnS nanoparticles (approximately 2-3 nm sphalerite) using temperature-programmed desorption (TPD). The activation energy for water desorption was derived as a function of the surface coverage through kinetic modeling of the experimental TPD curves. The binding energy of water equals the activation energy of desorption if it is assumed that the activation energy for adsorption is nearly zero. Molecular dynamics (MD) simulations of water adsorption on 3 and 5 nm sphalerite nanoparticles provided insights into the adsorption process and water binding at the atomic level. Water binds with the ZnS nanoparticle surface mainly via formation of Zn-O bonds. As compared with bulk ZnS crystals, ZnS nanoparticles can adsorb more water molecules per unit surface area due to the greatly increased curvature, which increases the distance between adjacent adsorbed molecules. Results from both TPD and MD show that the water binding energy increases with decreasing the water surface coverage. We attribute the increase in binding energy with decreasing surface water coverage to the increasing degree of surface under-coordination as removal of water molecules proceeds. MD also suggests that the water binding energy increases with decreasing particle size due to the further distance and hence lower interaction between adsorbed water molecules on highly curved smaller particle surfaces. Results also show that the binding energy, and thus the strength of interaction of water, is highest in isolated nanoparticles, lower in nanoparticle aggregates, and lowest in bulk crystals. Given that water binding is driven by surface energy reduction, we attribute the decreased binding energy for aggregated as compared to isolated particles to the decrease in surface energy that occurs as the result of inter-particle interactions. PMID:17518448

  3. On the interactions between nucleotide binding domains and membrane spanning domains in cystic fibrosis transmembrane regulator: A molecular dynamic study.

    PubMed

    Belmonte, Luca; Moran, Oscar

    2015-04-01

    The Cystic Fibrosis Transmembrane Regulator (CFTR) is a membrane protein whose mutations cause cystic fibrosis, a lethal genetic disease. We performed a molecular dynamic (MD) study of the properties of the nucleotide binding domains (NBD) whose conformational changes, upon ATP binding, are the direct responsible of the gating mechanisms of CFTR. This study was done for the wild type (WT) CFTR and for the two most common mutations, ΔF508, that produces a traffic defect of the protein, and the mutation G551D, that causes a gating defect on CFTR. Using an homology model of the open channel conformation of the CFTR we thus introduced the mutations to the structure. Although the overall structures of the G551D and ΔF508 are quite well conserved, the NBD1-NBD2 interactions are severely modified in both mutants. NBD1 and NBD2 are indeed destabilized with a higher internal energy (Ei) in the ΔF508-CFTR. Differently, Ei does not change in the NBDs of G551D but, while the number of close contacts between NBD1 and NBD2 in ΔF508 is increased, a significant reduction of close contacts is found in the G551D mutated form. Hydrogen bonds formation between NBDs of the two mutated forms is also altered and it is slightly increased for the ΔF508, while are severely reduced in G551D. A consequent modification of the NBDs-ICLs interactions between residues involved in the transduction of the ATP binding and the channel gating is also registered. Indeed, while a major interaction is noticed between NBDs interface and ICL2 and ICL4 in the WT, this interaction is somehow altered in both mutated forms plausibly with effect on channel gating. Thus, single point mutations of the CFTR protein can reasonably results in channel gating defects due to alteration of the interaction mechanisms between the NBDs and NBDs-ICLs interfaces upon ATP-binding process. PMID:25640670

  4. Exploring the Interaction of SV2A with Racetams Using Homology Modelling, Molecular Dynamics and Site-Directed Mutagenesis

    PubMed Central

    Lee, Joanna; Daniels, Veronique; Sands, Zara A.; Lebon, Florence; Shi, Jiye; Biggin, Philip C.

    2015-01-01

    The putative Major Facilitator Superfamily (MFS) transporter, SV2A, is the target for levetiracetam (LEV), which is a successful anti-epileptic drug. Furthermore, SV2A knock out mice display a severe seizure phenotype and die after a few weeks. Despite this, the mode of action of LEV is not known at the molecular level. It would be extremely desirable to understand this more fully in order to aid the design of improved anti-epileptic compounds. Since there is no structure for SV2A, homology modelling can provide insight into the ligand-binding site. However, it is not a trivial process to build such models, since SV2A has low sequence identity to those MFS transporters whose structures are known. A further level of complexity is added by the fact that it is not known which conformational state of the receptor LEV binds to, as multiple conformational states have been inferred by tomography and ligand binding assays or indeed, if binding is exclusive to a single state. Here, we explore models of both the inward and outward facing conformational states of SV2A (according to the alternating access mechanism for MFS transporters). We use a sequence conservation analysis to help guide the homology modelling process and generate the models, which we assess further with Molecular Dynamics (MD). By comparing the MD results in conjunction with docking and simulation of a LEV-analogue used in radioligand binding assays, we were able to suggest further residues that line the binding pocket. These were confirmed experimentally. In particular, mutation of D670 leads to a complete loss of binding. The results shed light on the way LEV analogues may interact with SV2A and may help with the on-going design of improved anti-epileptic compounds. PMID:25692762

  5. Open boundary molecular dynamics

    NASA Astrophysics Data System (ADS)

    Delgado-Buscalioni, R.; Sablić, J.; Praprotnik, M.

    2015-09-01

    This contribution analyzes several strategies and combination of methodologies to perform molecular dynamic simulations in open systems. Here, the term open indicates that the total system has boundaries where transfer of mass, momentum and energy can take place. This formalism, which we call Open Boundary Molecular Dynamics (OBMD), can act as interface of different schemes, such as Adaptive Resolution Scheme (AdResS) and Hybrid continuum-particle dynamics to link atomistic, coarse-grained (CG) and continuum (Eulerian) fluid dynamics in the general framework of fluctuating Navier-Stokes equations. The core domain of the simulation box is solved using all-atom descriptions. The CG layer introduced using AdResS is located at the outer part of the open box to make feasible the insertion of large molecules into the system. Communications between the molecular system and the outer world are carried out in the outer layers, called buffers. These coupling preserve momentum and mass conservation laws and can thus be linked with Eulerian hydro- dynamic solvers. In its simpler form, OBMD allows, however, to impose a local pressure tensor and a heat flux across the system's boundaries. For a one component molecular system, the external normal pressure and temperature determine the external chemical potential and thus the independent parameters of a grand-canonical ensemble simulation. Extended ensembles under non-equilibrium stationary states can also be simulated as well as time dependent forcings (e.g. oscillatory rheology). To illustrate the robustness of the combined OBMD-AdResS method, we present simulations of star-polymer melts at equilibrium and in sheared flow.

  6. Interaction of run-in edge dislocations with twist grain boundaries in Al-a molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Chandra, S.; Naveen Kumar, N.; Samal, M. K.; Chavan, V. M.; Patel, R. J.

    2016-06-01

    Grain boundaries play an important role in outlining the mechanical properties of crystalline materials. They act as sites for absorption/nucleation of dislocations, which are the main carriers of plastic deformation. In view of this, the interactions between edge dislocations and twist grain boundaries-dislocation pileup, dislocation absorption and dislocation emission were explored by performing molecular dynamics simulations in face-centered cubic Al using embedded atom method. The ?1 1 0? twist grain boundaries with various misorientation angles were selected for this purpose. It was found that the misorientation angle of boundary and stress anomalies arising from repeated dislocation absorption at the grain boundaries are the important parameters in determining the ability of the boundary to emit dislocations. Complex network of dislocations results in later stages of deformation, which may have a significant effect on the mechanical properties of the material. The peculiarities of dislocation nucleation, their emission from twist grain boundaries and the ramifications of this study towards development of higher length scale material models are discussed.

  7. dsRNA-protein interactions studied by molecular dynamics techniques. Unravelling dsRNA recognition by DCL1.

    PubMed

    Drusin, Salvador I; Suarez, Irina P; Gauto, Diego F; Rasia, Rodolfo M; Moreno, Diego M

    2016-04-15

    Double stranded RNA (dsRNA) participates in several biological processes, where RNA molecules acquire secondary structure inside the cell through base complementarity. The double stranded RNA binding domain (dsRBD) is one of the main protein folds that is able to recognize and bind to dsRNA regions. The N-terminal dsRBD of DCL1 in Arabidopsis thaliana (DCL1-1), in contrast to other studied dsRBDs, lacks a stable structure, behaving as an intrinsically disordered protein. DCL1-1 does however recognize dsRNA by acquiring a canonical fold in the presence of its substrate. Here we present a detailed modeling and molecular dynamics study of dsRNA recognition by DCL1-1. We found that DCL1-1 forms stable complexes with different RNAs and we characterized the residues involved in binding. Although the domain shows a binding loop substantially shorter than other homologs, it can still interact with the dsRNA and results in bending of the dsRNA A-type helix. Furthermore, we found that R8, a non-conserved residue located in the first dsRNA binding region, recognizes preferentially mismatched base pairs. We discuss our findings in the context of the function of DCL1-1 within the microRNA processing complex. PMID:26987516

  8. Structural insights into the interactions of xpt riboswitch with novel guanine analogues: a molecular dynamics simulation study.

    PubMed

    Jain, Swapan S; Sonavane, Uddhavesh B; Uppuladinne, Mallikarjunachari V N; McLaughlin, Emily C; Wang, Weiqing; Black, Sheneil; Joshi, Rajendra R

    2015-01-01

    Ligand recognition in purine riboswitches is a complex process requiring different levels of conformational changes. Recent efforts in the area of purine riboswitch research have focused on ligand analogue binding studies. In the case of the guanine xanthine phosphoribosyl transferase (xpt) riboswitch, synthetic analogues that resemble guanine have the potential to tightly bind and subsequently influence the genetic expression of xpt mRNA in prokaryotes. We have carried out 25 ns Molecular Dynamics (MD) simulation studies of the aptamer domain of the xpt G-riboswitch in four different states: guanine riboswitch in free form, riboswitch bound with its cognate ligand guanine, and with two guanine analogues SJ1 and SJ2. Our work reveals novel interactions of SJ1 and SJ2 ligands with the binding core residues of the riboswitch. The ligands proposed in this work bind to the riboswitch with greater overall stability and lower root mean square deviations and fluctuations compared to guanine ligand. Reporter gene assay data demonstrate that the ligand analogues, upon binding to the RNA, lower the genetic expression of the guanine riboswitch. Our work has important implications for future ligand design and binding studies in the exciting field of riboswitches. PMID:24404773

  9. Detection of non-native hydrophobic interactions in the denatured state of lysozyme by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Paci, Emanuele; Vendruscolo, Michele

    2005-05-01

    The presence of native and non-native hydrophobic clusters of amino acids has been detected experimentally for the protein hen egg white lysozyme even under strongly denaturing conditions. We characterize the structure of these hydrophobic clusters by two series of molecular dynamics simulations. The first series shows that in the wild type protein a non-native cluster formed by four tryptophan residues (W62, W63, W108 and W111) is formed with significant probability under denaturing conditions. In contrast, as observed experimentally and indicated by the second series of simulations presented here, the same cluster is formed much more rarely in the W62G mutant, which reduces the hydrophobicity of the polypeptide chain in the interface region between the two structural domains in the native state of the protein. These results support the observation that non-native interactions may play an important role in the folding process of complex proteins by stabilizing intermediate states in which hydrophobic groups are sequestered from the solvent and thus prevented from initiating aggregation.

  10. Interactions of aqueous amino acids and proteins with the (110) surface of ZnS in molecular dynamics simulations

    SciTech Connect

    Nawrocki, Grzegorz; Cieplak, Marek

    2014-03-07

    The growing usage of nanoparticles of zinc sulfide as quantum dots and biosensors calls for a theoretical assessment of interactions of ZnS with biomolecules. We employ the molecular-dynamics-based umbrella sampling method to determine potentials of mean force for 20 single amino acids near the ZnS (110) surface in aqueous solutions. We find that five amino acids do not bind at all and the binding energy of the remaining amino acids does not exceed 4.3 kJ/mol. Such energies are comparable to those found for ZnO (and to hydrogen bonds in proteins) but the nature of the specificity is different. Cysteine can bind with ZnS in a covalent way, e.g., by forming the disulfide bond with S in the solid. If this effect is included within a model incorporating the Morse potential, then the potential well becomes much deeper—the binding energy is close to 98 kJ/mol. We then consider tryptophan cage, a protein of 20 residues, and characterize its events of adsorption to ZnS. We demonstrate the relevance of interactions between the amino acids in the selection of optimal adsorbed conformations and recognize the key role of cysteine in generation of lasting adsorption. We show that ZnS is more hydrophobic than ZnO and that the density profile of water is quite different than that forming near ZnO—it has only a minor articulation into layers. Furthermore, the first layer of water is disordered and mobile.

  11. Interactions of aqueous amino acids and proteins with the (110) surface of ZnS in molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Nawrocki, Grzegorz; Cieplak, Marek

    2014-03-01

    The growing usage of nanoparticles of zinc sulfide as quantum dots and biosensors calls for a theoretical assessment of interactions of ZnS with biomolecules. We employ the molecular-dynamics-based umbrella sampling method to determine potentials of mean force for 20 single amino acids near the ZnS (110) surface in aqueous solutions. We find that five amino acids do not bind at all and the binding energy of the remaining amino acids does not exceed 4.3 kJ/mol. Such energies are comparable to those found for ZnO (and to hydrogen bonds in proteins) but the nature of the specificity is different. Cysteine can bind with ZnS in a covalent way, e.g., by forming the disulfide bond with S in the solid. If this effect is included within a model incorporating the Morse potential, then the potential well becomes much deeper—the binding energy is close to 98 kJ/mol. We then consider tryptophan cage, a protein of 20 residues, and characterize its events of adsorption to ZnS. We demonstrate the relevance of interactions between the amino acids in the selection of optimal adsorbed conformations and recognize the key role of cysteine in generation of lasting adsorption. We show that ZnS is more hydrophobic than ZnO and that the density profile of water is quite different than that forming near ZnO—it has only a minor articulation into layers. Furthermore, the first layer of water is disordered and mobile.

  12. Interactions of aqueous amino acids and proteins with the (110) surface of ZnS in molecular dynamics simulations.

    PubMed

    Nawrocki, Grzegorz; Cieplak, Marek

    2014-03-01

    The growing usage of nanoparticles of zinc sulfide as quantum dots and biosensors calls for a theoretical assessment of interactions of ZnS with biomolecules. We employ the molecular-dynamics-based umbrella sampling method to determine potentials of mean force for 20 single amino acids near the ZnS (110) surface in aqueous solutions. We find that five amino acids do not bind at all and the binding energy of the remaining amino acids does not exceed 4.3 kJ/mol. Such energies are comparable to those found for ZnO (and to hydrogen bonds in proteins) but the nature of the specificity is different. Cysteine can bind with ZnS in a covalent way, e.g., by forming the disulfide bond with S in the solid. If this effect is included within a model incorporating the Morse potential, then the potential well becomes much deeper--the binding energy is close to 98 kJ/mol. We then consider tryptophan cage, a protein of 20 residues, and characterize its events of adsorption to ZnS. We demonstrate the relevance of interactions between the amino acids in the selection of optimal adsorbed conformations and recognize the key role of cysteine in generation of lasting adsorption. We show that ZnS is more hydrophobic than ZnO and that the density profile of water is quite different than that forming near ZnO--it has only a minor articulation into layers. Furthermore, the first layer of water is disordered and mobile. PMID:24606380

  13. Interactions of hydrogen with the iron and iron carbide interfaces: a ReaxFF molecular dynamics study.

    PubMed

    Islam, Md Mahbubul; Zou, Chenyu; van Duin, Adri C T; Raman, Sumathy

    2016-01-14

    Hydrogen embrittlement (HE) is a well-known material phenomenon that causes significant loss in the mechanical strength of structural iron and often leads to catastrophic failures. In order to provide a detailed atomistic description of HE we have used a reactive bond order potential to adequately describe the diffusion of hydrogen as well as its chemical interaction with other hydrogen atoms, defects, and the host metal. The currently published ReaxFF force field for Fe/C/H systems was originally developed to describe Fischer-Tropsch (FT) catalysis [C. Zou, A. C. T. van Duin and D. C. Sorescu, Top. Catal., 2012, 55, 391-401], and especially had been trained for surface formation energies, binding energies of small hydrocarbon radicals on different surfaces of iron and the barrier heights of surface reactions. We merged this force field with the latest ReaxFF carbon parameters [S. Goverapet Srinivasan, A. C. T. van Duin and P. Ganesh, J. Phys. Chem. A, 2015, 119, 1089-5639] and used the same training data set to refit the Fe/C interaction parameters. The present work is focused on evaluating the applicability of this reactive force field to describe material characteristics and study the role of defects and impurities in the bulk and at the precipitator interfaces. We study the interactions of hydrogen with pure and defective α-iron (ferrite), Fe3C (cementite), and ferrite-cementite interfaces with a vacancy cluster. We also investigate the growth of nanovoids in α-iron using a grand canonical Monte Carlo (GCMC) scheme. The calculated hydrogen diffusion coefficients for both ferrite and cementite phases predict a decrease in the work of separation with increasing hydrogen concentration at the ferrite-cementite interface, suggesting a hydrogen-induced decohesion behavior. Hydrogen accumulation at the interface was observed during molecular dynamics (MD) simulations, which is consistent with experimental findings. These results demonstrate the ability of the Reax

  14. Molecular Dynamics of Acetylcholinesterase

    SciTech Connect

    Shen, T Y.; Tai, Kaihsu; Henchman, Richard H.; Mccammon, Andy

    2002-06-01

    Molecular dynamics simulations are leading to a deeper understanding of the activity of the enzyme acetylcholinesterase. Simulations have shown how breathing motions in the enzyme facilitate the displacement of substrate from the surface of the enzyme to the buried active site. The most recent work points to the complex and spatially extensive nature of such motions and suggests possible modes of regulation of the activity of the enzyme.

  15. Defect-Enhanced Charge Transfer by Ion-Solid Interactions in SiC using Large-Scale Ab Initio Molecular Dynamics Simulations

    SciTech Connect

    Gao, Fei; Xiao, H. Y.; Zu, Xiaotao T.; Posselt, Matthias; Weber, William J.

    2009-07-10

    Large-scale ab initio molecular dynamics simulations of ion-solid interactions in SiC reveal that significant charge-transfer occurs between atoms and defects can enhance charge transfer to surrounding atoms. The results demonstrate that charge transfer to and from recoiling atoms can alter the energy barriers and dynamics for stable defect formation. The present simulations illustrate in detail the dynamic processes for charged defect formation. The averaged values of displacement threshold energies along four main crystallographic directions are smaller than those determined by empirical potentials due to charge transfer effects on recoil atoms.

  16. Defect-Enhanced Charge Transfer by Ion-Solid Interactions in SiC using Large-Scale Ab Initio Molecular Dynamics Simulations

    SciTech Connect

    Gao Fei; Weber, William J.; Xiao Haiyan; Zu Xiaotao; Posselt, Matthias

    2009-07-10

    Large-scale ab initio molecular dynamics simulations of ion-solid interactions in SiC reveal that significant charge transfer occurs between atoms, and defects can enhance charge transfer to surrounding atoms. The results demonstrate that charge transfer to and from recoiling atoms can alter the energy barriers and dynamics for stable defect formation. The present simulations illustrate in detail the dynamic processes for charged defect formation. The averaged values of displacement threshold energies along four main crystallographic directions are smaller than those determined by empirical potentials due to charge-transfer effects on recoil atoms.

  17. Parallel Molecular Dynamics Program for Molecules

    Energy Science and Technology Software Center (ESTSC)

    1995-03-07

    ParBond is a parallel classical molecular dynamics code that models bonded molecular systems, typically of an organic nature. It uses classical force fields for both non-bonded Coulombic and Van der Waals interactions and for 2-, 3-, and 4-body bonded (bond, angle, dihedral, and improper) interactions. It integrates Newton''s equation of motion for the molecular system and evaluates various thermodynamical properties of the system as it progresses.

  18. Cholesterol-Ceramide Interactions in Phospholipid and Sphingolipid Bilayers As Observed by Positron Annihilation Lifetime Spectroscopy and Molecular Dynamics Simulations.

    PubMed

    García-Arribas, Aritz B; Axpe, Eneko; Mujika, Jon Iñaki; Mérida, David; Busto, Jon V; Sot, Jesús; Alonso, Alicia; Lopez, Xabier; García, Jose Ángel; Ugalde, Jesus M; Plazaola, Fernando; Goñi, Félix M

    2016-05-31

    Free volume voids in lipid bilayers can be measured by positron annihilation lifetime spectroscopy (PALS). This technique has been applied, together with differential scanning calorimetry and molecular dynamics (MD) simulations, to study the effects of cholesterol (Chol) and ceramide (Cer) on free volume voids in sphingomyelin (SM) or dipalmitoylphosphatidylcholine (DPPC) bilayers. Binary lipid samples with Chol were studied (DPPC:Chol 60:40, SM:Chol 60:40 mol ratio), and no phase transition was detected in the 20-60 °C range, in agreement with calorimetric data. Chol-driven liquid-ordered phase showed an intermediate free volume void size as compared to gel and fluid phases. For SM and SM:Cer (85:15 mol:mol) model membranes measured in the 20-60 °C range the gel-to-fluid phase transition could be observed with a related increase in free volume, which was more pronounced for the SM:Cer sample. MD simulations suggest a hitherto unsuspected lipid tilting in SM:Cer bilayers but not in pure SM. Ternary samples of DPPC:Cer:Chol (54:23:23) and SM:Cer:Chol (54:23:23) were measured, and a clear pattern of free volume increase was observed in the 20-60 °C because of the gel-to-fluid transition. Interestingly, MD simulations showed a tendency of Cer to change its distribution along the membrane to make room for Chol in ternary mixtures. The results suggest that the gel phase formed in these ternary mixtures is stabilized by Chol-Cer interactions. PMID:27158737

  19. Interactions of the C-terminal Domain of Human Ku70 with DNA Substrate: A Molecular Dynamics Study

    NASA Technical Reports Server (NTRS)

    Hu, Shaowen; Huff, Janice; Pluth, Janice M.; Cucinotta, Francis A.

    2007-01-01

    NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku(sub 70/80) complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The C-terminal domain of Ku70 (Ku70c, residues 559-609), contains an helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the Ku70c/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the subunit Ku70c and a 14 base pairs DNA duplex, whose starting structures are designed to be variable so as to mimic their different binding modes. By analyzing conformational changes and energetic properties of the complex during MD simulations, we found that interactions are preferred at DNA ends, and within the major groove, which is consistent with previous experimental investigations. In addition, the results indicate that cooperation of Ku70c with other subunits of Ku(sub 70/80) is necessary to explain the high affinity of binding as observed in experiments.

  20. Interactive Modelling of Molecular Structures

    NASA Astrophysics Data System (ADS)

    Rustad, J. R.; Kreylos, O.; Hamann, B.

    2004-12-01

    The "Nanotech Construction Kit" (NCK) [1] is a new project aimed at improving the understanding of molecular structures at a nanometer-scale level by visualization and interactive manipulation. Our very first prototype is a virtual-reality program allowing the construction of silica and carbon structures from scratch by assembling them one atom at a time. In silica crystals or glasses, the basic building block is an SiO4 unit, with the four oxygen atoms arranged around the central silicon atom in the shape of a regular tetrahedron. Two silicate units can connect to each other by their silicon atoms covalently bonding to one shared oxygen atom. Geometrically, this means that two tetrahedra can link at their vertices. Our program is based on geometric representations and uses simple force fields to simulate the interaction of building blocks, such as forming/breaking of bonds and repulsion. Together with stereoscopic visualization and direct manipulation of building blocks using wands or data gloves, this enables users to create realistic and complex molecular models in short amounts of time. The NCK can either be used as a standalone tool, to analyze or experiment with molecular structures, or it can be used in combination with "traditional" molecular dynamics (MD) simulations. In a first step, the NCK can create initial configurations for subsequent MD simulation. In a more evolved setup, the NCK can serve as a visual front-end for an ongoing MD simulation, visualizing changes in simulation state in real time. Additionally, the NCK can be used to change simulation state on-the-fly, to experiment with different simulation conditions, or force certain events, e.g., the forming of a bond, and observe the simulation's reaction. [1] http://graphics.cs.ucdavis.edu/~okreylos/ResDev/NanoTech

  1. Molecular ions, Rydberg spectroscopy and dynamics

    SciTech Connect

    Jungen, Ch.

    2015-01-22

    Ion spectroscopy, Rydberg spectroscopy and molecular dynamics are closely related subjects. Multichannel quantum defect theory is a theoretical approach which draws on this close relationship and thereby becomes a powerful tool for the study of systems consisting of a positively charged molecular ion core interacting with an electron which may be loosely bound or freely scattering.

  2. Influence of the R823W mutation on the interaction of the ANKS6-ANKS3: insights from molecular dynamics simulation and free energy analysis.

    PubMed

    Kan, Wei; Fang, Fengqin; Chen, Lin; Wang, Ruige; Deng, Qigang

    2016-05-01

    The sterile alpha motif (SAM) domain of the protein ANKS6, a protein-protein interaction domain, is responsible for autosomal dominant polycystic kidney disease. Although the disease is the result of the R823W point mutation in the SAM domain of the protein ANKS6, the molecular details are still unclear. We applied molecular dynamics simulations, the principal component analysis, and the molecular mechanics Poisson-Boltzmann surface area binding free energy calculation to explore the structural and dynamic effects of the R823W point mutation on the complex ANKS6-ANKS3 (PDB ID: 4NL9) in comparison to the wild proteins. The energetic analysis presents that the wild type has a more stable structure than the mutant. The R823W point mutation not only disrupts the structure of the ANKS6 SAM domain but also negatively affects the interaction of the ANKS6-ANKS3. These results further clarify the previous experiments to understand the ANKS6-ANKS3 interaction comprehensively. In summary, this study would provide useful suggestions to understand the interaction of these proteins and their fatal action on mediating kidney function. PMID:26295479

  3. Introduction to Accelerated Molecular Dynamics

    SciTech Connect

    Perez, Danny

    2012-07-10

    Molecular Dynamics is the numerical solution of the equations of motion of a set of atoms, given an interatomic potential V and some boundary and initial conditions. Molecular Dynamics is the largest scale model that gives unbiased dynamics [x(t),p(t)] in full atomistic detail. Molecular Dynamics: is simple; is 'exact' for classical dynamics (with respect to a given V); can be used to compute any (atomistic) thermodynamical or dynamical properties; naturally handles complexity -- the system does the right thing at the right time. The physics derives only from the interatomic potential.

  4. Molecular Dynamics Calculations

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The development of thermodynamics and statistical mechanics is very important in the history of physics, and it underlines the difficulty in dealing with systems involving many bodies, even if those bodies are identical. Macroscopic systems of atoms typically contain so many particles that it would be virtually impossible to follow the behavior of all of the particles involved. Therefore, the behavior of a complete system can only be described or predicted in statistical ways. Under a grant to the NASA Lewis Research Center, scientists at the Case Western Reserve University have been examining the use of modern computing techniques that may be able to investigate and find the behavior of complete systems that have a large number of particles by tracking each particle individually. This is the study of molecular dynamics. In contrast to Monte Carlo techniques, which incorporate uncertainty from the outset, molecular dynamics calculations are fully deterministic. Although it is still impossible to track, even on high-speed computers, each particle in a system of a trillion trillion particles, it has been found that such systems can be well simulated by calculating the trajectories of a few thousand particles. Modern computers and efficient computing strategies have been used to calculate the behavior of a few physical systems and are now being employed to study important problems such as supersonic flows in the laboratory and in space. In particular, an animated video (available in mpeg format--4.4 MB) was produced by Dr. M.J. Woo, now a National Research Council fellow at Lewis, and the G-VIS laboratory at Lewis. This video shows the behavior of supersonic shocks produced by pistons in enclosed cylinders by following exactly the behavior of thousands of particles. The major assumptions made were that the particles involved were hard spheres and that all collisions with the walls and with other particles were fully elastic. The animated video was voted one of two

  5. Ab initio molecular orbital-configuration interaction based quantum master equation (MOQME) approach to the dynamic first hyperpolarizabilities of asymmetric π-conjugated systems

    SciTech Connect

    Kishi, Ryohei; Fujii, Hiroaki; Minami, Takuya; Shigeta, Yasuteru; Nakano, Masayoshi

    2015-01-22

    In this study, we apply the ab initio molecular orbital - configuration interaction based quantum master equation (MOQME) approach to the calculation and analysis of the dynamic first hyperpolarizabilities (β) of asymmetric π-conjugated molecules. In this approach, we construct the excited state models by the ab initio configuration interaction singles method. Then, time evolutions of system reduced density matrix ρ(t) and system polarization p(t) are calculated by the QME approach. Dynamic β in the second harmonic generation is calculated based on the nonperturbative definition of nonlinear optical susceptibility, using the frequency domain system polarization p(ω). Spatial contributions of electrons to β are analyzed based on the dynamic hyperpolarizability density map, which visualizes the second-order response of charge density oscillating with a frequency of 2ω. We apply the present method to the calculation of the dynamic β of a series of donor/acceptor substituted polyene oligomers, and then discuss the applicability of the MOQME method to the calculation and analysis of dynamic NLO properties of molecular systems.

  6. Specific ion interactions with aromatic rings in aqueous solutions: Comparison of molecular dynamics simulations with a thermodynamic solute partitioning model and Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Vincent, Jordan C.; Matt, Sarah M.; Rankin, Blake M.; D'Auria, Raffaella; Freites, J. Alfredo; Ben-Amotz, Dor; Tobias, Douglas J.

    2015-10-01

    Specific ion interactions of KF, and the Na+ salts of SO42-, F-, Cl-, NO3-, I-, and ClO4- with benzene in aqueous solutions were investigated using molecular dynamics simulations and compared with experimental Raman multivariate curve resolution (Raman-MCR) and thermodynamic results. Good agreement is found with the hydration-shell partition coefficients of salts obtained from the thermodynamic analysis and of halogen anions obtained from the Raman-MCR spectra of benzene and pyridine. Larger discrepancies between the simulation and thermodynamic cation partitioning results point to the influence of counter-ion interaction on cation partitioning.

  7. Molecular dynamics simulations

    SciTech Connect

    Alder, B.J.

    1985-07-01

    The molecular dynamics computer simulation discovery of the slow decay of the velocity autocorrelation function in fluids is briefly reviewed in order to contrast that long time tail with those observed for the stress autocorrelation function in fluids and the velocity autocorrelation function in the Lorentz gas. For a non-localized particle in the Lorentz gas it is made plausible that even if it behaved quantum mechanically its long time tail would be the same as the classical one. The generalization of Fick's law for diffusion for the Lorentz gas, necessary to avoid divergences due to the slow decay of correlations, is presented. For fluids, that generalization has not yet been established, but the region of validity of generalized hydrodynamics is discussed. 20 refs., 5 figs.

  8. Selective IR multiphoton dissociation of molecules in a pulsed gas-dynamically cooled molecular flow interacting with a solid surface as an alternative to low-energy methods of molecular laser isotope separation

    NASA Astrophysics Data System (ADS)

    Makarov, G. N.; Petin, A. N.

    2016-03-01

    We report the results of studies on the isotope-selective infrared multiphoton dissociation (IR MFD) of SF6 and CF3I molecules in a pulsed, gas-dynamically cooled molecular flow interacting with a solid surface. The productivity of this method in the conditions of a specific experiment (by the example of SF6 molecules) is evaluated. A number of low-energy methods of molecular laser isotope separation based on the use of infrared lasers for selective excitation of molecules are analysed and their productivity is estimated. The methods are compared with those of selective dissociation of molecules in the flow interacting with a surface. The advantages of this method compared to the low-energy methods of molecular laser isotope separation and the IR MPD method in the unperturbed jets and flows are shown. It is concluded that this method could be a promising alternative to the low-energy methods of molecular laser isotope separation.

  9. A molecular dynamics study of model SI clathrate hydrates: the effect of guest size and guest-water interaction on decomposition kinetics.

    PubMed

    Das, Subhadip; Baghel, Vikesh Singh; Roy, Sudip; Kumar, Rajnish

    2015-04-14

    One of the options suggested for methane recovery from natural gas hydrates is molecular replacement of methane by suitable guests like CO2 and N2. This approach has been found to be feasible through many experimental and molecular dynamics simulation studies. However, the long term stability of the resultant hydrate needs to be evaluated; the decomposition rate of these hydrates is expected to depend on the interaction between these guest and water molecules. In this work, molecular dynamics simulation has been performed to illustrate the effect of guest molecules with different sizes and interaction strengths with water on structure I (SI) hydrate decomposition and hence the stability. The van der Waals interaction between water of hydrate cages and guest molecules is defined by Lennard Jones potential parameters. A wide range of parameter spaces has been scanned by changing the guest molecules in the SI hydrate, which acts as a model gas for occupying the small and large cages of the SI hydrate. All atomistic simulation results show that the stability of the hydrate is sensitive to the size and interaction of the guest molecules with hydrate water. The increase in the interaction of guest molecules with water stabilizes the hydrate, which in turn shows a slower rate of hydrate decomposition. Similarly guest molecules with a reasonably small (similar to Helium) or large size increase the decomposition rate. The results were also analyzed by calculating the structural order parameter to understand the dynamics of crystal structure and correlated with the release rate of guest molecules from the solid hydrate phase. The results have been explained based on the calculation of potential energies felt by guest molecules in amorphous water, hydrate bulk and hydrate-water interface regions. PMID:25767053

  10. Molecular dynamics simulation of benzene

    NASA Astrophysics Data System (ADS)

    Trumpakaj, Zygmunt; Linde, Bogumił B. J.

    2016-03-01

    Intermolecular potentials and a few models of intermolecular interaction in liquid benzene are tested by Molecular Dynamics (MD) simulations. The repulsive part of the Lennard-Jones 12-6 (LJ 12-6) potential is too hard, which yields incorrect results. The exp-6 potential with a too hard repulsive term is also often used. Therefore, we took an expa-6 potential with a small Gaussian correction plus electrostatic interactions. This allows to modify the curvature of the potential. The MD simulations are carried out in the temperature range 280-352 K under normal pressure and at experimental density. The Rayleigh scattering of depolarized light is used for comparison. The results of MD simulations are comparable with the experimental values.

  11. Interaction Networks in Protein Folding via Atomic-Resolution Experiments and Long-Time-Scale Molecular Dynamics Simulations

    PubMed Central

    2015-01-01

    The integration of atomic-resolution experimental and computational methods offers the potential for elucidating key aspects of protein folding that are not revealed by either approach alone. Here, we combine equilibrium NMR measurements of thermal unfolding and long molecular dynamics simulations to investigate the folding of gpW, a protein with two-state-like, fast folding dynamics and cooperative equilibrium unfolding behavior. Experiments and simulations expose a remarkably complex pattern of structural changes that occur at the atomic level and from which the detailed network of residue–residue couplings associated with cooperative folding emerges. Such thermodynamic residue–residue couplings appear to be linked to the order of mechanistically significant events that take place during the folding process. Our results on gpW indicate that the methods employed in this study are likely to prove broadly applicable to the fine analysis of folding mechanisms in fast folding proteins. PMID:25924808

  12. Interaction Networks in Protein Folding via Atomic-Resolution Experiments and Long-Time-Scale Molecular Dynamics Simulations.

    PubMed

    Sborgi, Lorenzo; Verma, Abhinav; Piana, Stefano; Lindorff-Larsen, Kresten; Cerminara, Michele; Santiveri, Clara M; Shaw, David E; de Alba, Eva; Muñoz, Victor

    2015-05-27

    The integration of atomic-resolution experimental and computational methods offers the potential for elucidating key aspects of protein folding that are not revealed by either approach alone. Here, we combine equilibrium NMR measurements of thermal unfolding and long molecular dynamics simulations to investigate the folding of gpW, a protein with two-state-like, fast folding dynamics and cooperative equilibrium unfolding behavior. Experiments and simulations expose a remarkably complex pattern of structural changes that occur at the atomic level and from which the detailed network of residue-residue couplings associated with cooperative folding emerges. Such thermodynamic residue-residue couplings appear to be linked to the order of mechanistically significant events that take place during the folding process. Our results on gpW indicate that the methods employed in this study are likely to prove broadly applicable to the fine analysis of folding mechanisms in fast folding proteins. PMID:25924808

  13. Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics.

    PubMed

    Yamamoto, Eiji; Kalli, Antreas C; Yasuoka, Kenji; Sansom, Mark S P

    2016-08-01

    A molecular simulation pipeline for determining the mode of interaction of pleckstrin homology (PH) domains with phosphatidylinositol phosphate (PIP)-containing lipid bilayers is presented. We evaluate our methodology for the GRP1 PH domain via comparison with structural and biophysical data. Coarse-grained simulations yield a 2D density landscape for PH/membrane interactions alongside residue contact profiles. Predictions of the membrane localization and interactions of 13 PH domains reveal canonical, non-canonical, and dual PIP-binding sites on the proteins. Thus, the PH domains associate with the PIP molecules in the membrane via a highly positively charged loop. Some PH domains exhibit modes of interaction with PIP-containing membranes additional to this canonical binding mode. All 13 PH domains cause a degree of local clustering of PIP molecules upon binding to the membrane. This provides a global picture of PH domain interactions with membranes. The high-throughput approach could be extended to other families of peripheral membrane proteins. PMID:27427480

  14. Dynamics of Galaxy Interactions

    NASA Astrophysics Data System (ADS)

    Barnes, Joshua E.

    Preface Theory of Interacting Galaxies The Role of Gravity Holmberg's Work on Tidal Interactions "Galactic Bridges and Tails" Dark Matter Numerical Stellar Dynamics Collisionless Stellar Systems Simulating the Stars Force Calculation Time Integration Errors and Relaxation Effects Initial Conditions Numerical Gas Dynamics A Sketch of the Interstellar Medium Simulating the ISM Gas in B/D/H Models Tidal Interactions Test-Particle Studies: Bridges and Tails Self-Consistent Studies Bars and Spirals Tidal Dwarf Galaxies Self-Consistent "Lookalikes" Getting the Feel of the Antennae Sneaking Up on the Mice What Happened to the Whirlpool? Unresolved Issues Mechanics of Merging Tidal Drag Orbit Decay Violent Relaxation Final Encounters Remnant Structure Phase Mixing Characteristics Scales Radial Profiles Shapes and Kinematics Orbit Structure Gas Dynamics in Mergers Inflows in Perturbed Disks Merging Encounters Remnant Structure Dissipation and Stellar Backlash Galaxy transformation and the Arrow of Time

  15. Floating orbital molecular dynamics simulations.

    PubMed

    Perlt, Eva; Brüssel, Marc; Kirchner, Barbara

    2014-04-21

    We introduce an alternative ab initio molecular dynamics simulation as a unification of Hartree-Fock molecular dynamics and the floating orbital approach. The general scheme of the floating orbital molecular dynamics method is presented. Moreover, a simple but sophisticated guess for the orbital centers is provided to reduce the number of electronic structure optimization steps at each molecular dynamics step. The conservation of total energy and angular momentum is investigated in order to validate the floating orbital molecular dynamics approach with and without application of the initial guess. Finally, a water monomer and a water dimer are simulated, and the influence of the orbital floating on certain properties like the dipole moment is investigated. PMID:24600690

  16. Radiation in molecular dynamic simulations

    SciTech Connect

    Glosli, J; Graziani, F; More, R; Murillo, M; Streitz, F; Surh, M

    2008-10-13

    Hot dense radiative (HDR) plasmas common to Inertial Confinement Fusion (ICF) and stellar interiors have high temperature (a few hundred eV to tens of keV), high density (tens to hundreds of g/cc) and high pressure (hundreds of Megabars to thousands of Gigabars). Typically, such plasmas undergo collisional, radiative, atomic and possibly thermonuclear processes. In order to describe HDR plasmas, computational physicists in ICF and astrophysics use atomic-scale microphysical models implemented in various simulation codes. Experimental validation of the models used to describe HDR plasmas are difficult to perform. Direct Numerical Simulation (DNS) of the many-body interactions of plasmas is a promising approach to model validation but, previous work either relies on the collisionless approximation or ignores radiation. We present a new numerical simulation technique to address a currently unsolved problem: the extension of molecular dynamics to collisional plasmas including emission and absorption of radiation. The new technique passes a key test: it relaxes to a blackbody spectrum for a plasma in local thermodynamic equilibrium. This new tool also provides a method for assessing the accuracy of energy and momentum exchange models in hot dense plasmas. As an example, we simulate the evolution of non-equilibrium electron, ion, and radiation temperatures for a hydrogen plasma using the new molecular dynamics simulation capability.

  17. Ab initio molecular dynamics simulations of ion-solid interactions in zirconate pyrochlores

    SciTech Connect

    Xiao, Haiyan Y.; Weber, William J.; Zhang, Yanwen; Zu, X. T.

    2015-01-31

    In this paper, an ab initio molecular dynamics method is employed to study low energy recoil events in zirconate pyrochlores (A2Zr2O7, A = La, Nd and Sm). It shows that both cations and anions in Nd2Zr2O7 and Sm2Zr2O7 are generally more likely to be displaced than those in La2Zr2O7. The damage end states mainly consist of Frenkel pair defects, and the Frenkel pair formation energies in Nd2Zr2O7 and Sm2Zr2O7 are lower than those in La2Zr2O7. These results suggest that the order–disorder structural transition more easily occurs in Nd2Zr2O7 and Sm2Zr2O7 resulting in a defect-fluorite structure, which agrees well with experimental observations. Our calculations indicate that oxygen migration from 48f and 8b to 8a sites is dominant under low energy irradiation. A number of new defects, including four types of cation Frenkel pairs and six types of anion Frenkel pairs, are revealed by ab initio molecular dynamics simulations. The present findings may help to advance the fundamental understanding of the irradiation response behavior of zirconate pyrochlores.

  18. Improved Parameterization of Amine-Carboxylate and Amine-Phosphate Interactions for Molecular Dynamics Simulations Using the CHARMM and AMBER Force Fields.

    PubMed

    Yoo, Jejoong; Aksimentiev, Aleksei

    2016-01-12

    Over the past decades, molecular dynamics (MD) simulations of biomolecules have become a mainstream biophysics technique. As the length and time scales amenable to the MD method increase, shortcomings of the empirical force fields, which have been developed and validated using relatively short simulations of small molecules, become apparent. One common artifact is aggregation of water-soluble biomolecules driven by artificially strong charge-charge interactions. Here, we report a systematic atom pair-specific refinement of Lennard-Jones parameters (NBFIX) describing amine-carboxylate and amine-phosphate interactions, which bring MD simulations of basic peptide-mediated nucleic acid assemblies and lipid bilayer membranes into better agreement with experimental data. As our refinement does not affect the existing parametrization of bonded interactions or alter the solvation free energies, it improves the realism of an MD simulation without introducing additional artifacts. PMID:26632962

  19. Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?

    PubMed

    Ratnaparkhi, Aditi; Muthu, Shivani A; Shiriskar, Sonali M; Pissurlenkar, Raghuvir R S; Choudhary, Sinjan; Ahmad, Basir

    2015-09-01

    Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation. The HESP-HEWL binding studies were performed using a fluorescence quenching technique, molecular docking and molecular dynamics simulations. We found a strong interaction of HESP with the lysozyme monomer (Ka, ~ 5 × 10(4) M(-1)) mainly through hydrogen bonding, water bridges, and hydrophobic interactions. We showed that HESP molecule spanned the highly aggregation prone region (amino acid residues 48-101) of HEWL and prevented its fibrillar aggregation. Further, we found that HESP binding completely inhibited amorphous aggregation of the protein induced by disulfide-reducing agent tries-(2-carboxyethyl) phosphine. Conformational and stability studies as followed by various tertiary and secondary structure probes revealed that HESP binding only marginally affected the lysozyme monomer conformation and increased both stability and reversibility of the protein against thermal denaturation. Future studies should investigate detail effects of HESP on solvent dynamics, structure, and toxicity of various aggregates. The answers to these questions will not only target the basic sciences, but also have application in biomedical and biotechnological sciences. PMID:25301518

  20. Theoretical studies of molecular interactions

    SciTech Connect

    Lester, W.A. Jr.

    1993-12-01

    This research program is directed at extending fundamental knowledge of atoms and molecules including their electronic structure, mutual interaction, collision dynamics, and interaction with radiation. The approach combines the use of ab initio methods--Hartree-Fock (HF) multiconfiguration HF, configuration interaction, and the recently developed quantum Monte Carlo (MC)--to describe electronic structure, intermolecular interactions, and other properties, with various methods of characterizing inelastic and reaction collision processes, and photodissociation dynamics. Present activity is focused on the development and application of the QMC method, surface catalyzed reactions, and reorientation cross sections.

  1. Molecular dynamics simulation and experimental verification of the interaction between cyclin T1 and HIV-1 Tat proteins.

    PubMed

    Asamitsu, Kaori; Hirokawa, Takatsugu; Hibi, Yurina; Okamoto, Takashi

    2015-01-01

    The viral encoded Tat protein is essential for the transcriptional activation of HIV proviral DNA. Interaction of Tat with a cellular transcription elongation factor P-TEFb containing CycT1 is critically required for its action. In this study, we performed MD simulation using the 3D data for wild-type and 4CycT1mutants3D data. We found that the dynamic structural change of CycT1 H2' helix is indispensable for its activity for the Tat action. Moreover, we detected flexible structural changes of the Tat-recognition cavity in the WT CycT1 comprising of ten AAs that are in contact with Tat. These structural fluctuations in WT were lost in the CycT1 mutants. We also found the critical importance of the hydrogen bond network involving H1, H1' and H2 helices of CycT1. Since similar AA substitutions of the Tat-CycT1 chimera retained the Tat-supporting activity, these interactions are considered primarily involved in interaction with Tat. These findings described in this paper should provide vital information for the development of effective anti-Tat compound. PMID:25781978

  2. Molecular dynamics of protein A and a WW domain with a united-residue model including hydrodynamic interaction.

    PubMed

    Lipska, Agnieszka G; Seidman, Steven R; Sieradzan, Adam K; Giełdoń, Artur; Liwo, Adam; Scheraga, Harold A

    2016-05-14

    The folding of the N-terminal part of the B-domain of staphylococcal protein A (PDB ID: 1BDD, a 46-residue three-α-helix bundle) and the formin-binding protein 28 WW domain (PDB ID: 1E0L, a 37-residue three-stranded anti-parallel β protein) was studied by means of Langevin dynamics with the coarse-grained UNRES force field to assess the influence of hydrodynamic interactions on protein-folding pathways and kinetics. The unfolded, intermediate, and native-like structures were identified by cluster analysis, and multi-exponential functions were fitted to the time dependence of the fractions of native and intermediate structures, respectively, to determine bulk kinetics. It was found that introducing hydrodynamic interactions slows down both the formation of an intermediate state and the transition from the collapsed structures to the final native-like structures by creating multiple kinetic traps. Therefore, introducing hydrodynamic interactions considerably slows the folding, as opposed to the results obtained from earlier studies with the use of Gō-like models. PMID:27179474

  3. Molecular Dynamics Simulation and Experimental Verification of the Interaction between Cyclin T1 and HIV-1 Tat Proteins

    PubMed Central

    Asamitsu, Kaori; Hibi, Yurina

    2015-01-01

    The viral encoded Tat protein is essential for the transcriptional activation of HIV proviral DNA. Interaction of Tat with a cellular transcription elongation factor P-TEFb containing CycT1 is critically required for its action. In this study, we performed MD simulation using the 3D data for wild-type and 4CycT1mutants3D data. We found that the dynamic structural change of CycT1 H2’ helix is indispensable for its activity for the Tat action. Moreover, we detected flexible structural changes of the Tat-recognition cavity in the WT CycT1 comprising of ten AAs that are in contact with Tat. These structural fluctuations in WT were lost in the CycT1 mutants. We also found the critical importance of the hydrogen bond network involving H1, H1’ and H2 helices of CycT1. Since similar AA substitutions of the Tat-CycT1 chimera retained the Tat-supporting activity, these interactions are considered primarily involved in interaction with Tat. These findings described in this paper should provide vital information for the development of effective anti-Tat compound. PMID:25781978

  4. Molecular dynamics of protein A and a WW domain with a united-residue model including hydrodynamic interaction

    NASA Astrophysics Data System (ADS)

    Lipska, Agnieszka G.; Seidman, Steven R.; Sieradzan, Adam K.; Giełdoń, Artur; Liwo, Adam; Scheraga, Harold A.

    2016-05-01

    The folding of the N-terminal part of the B-domain of staphylococcal protein A (PDB ID: 1BDD, a 46-residue three-α-helix bundle) and the formin-binding protein 28 WW domain (PDB ID: 1E0L, a 37-residue three-stranded anti-parallel β protein) was studied by means of Langevin dynamics with the coarse-grained UNRES force field to assess the influence of hydrodynamic interactions on protein-folding pathways and kinetics. The unfolded, intermediate, and native-like structures were identified by cluster analysis, and multi-exponential functions were fitted to the time dependence of the fractions of native and intermediate structures, respectively, to determine bulk kinetics. It was found that introducing hydrodynamic interactions slows down both the formation of an intermediate state and the transition from the collapsed structures to the final native-like structures by creating multiple kinetic traps. Therefore, introducing hydrodynamic interactions considerably slows the folding, as opposed to the results obtained from earlier studies with the use of Gō-like models.

  5. Probing Allosteric Inhibition Mechanisms of the Hsp70 Chaperone Proteins Using Molecular Dynamics Simulations and Analysis of the Residue Interaction Networks.

    PubMed

    Stetz, Gabrielle; Verkhivker, Gennady M

    2016-08-22

    Although molecular mechanisms of allosteric regulation in the Hsp70 chaperones have been extensively studied at both structural and functional levels, the current understanding of allosteric inhibition of chaperone activities by small molecules is still lacking. In the current study, using a battery of computational approaches, we probed allosteric inhibition mechanisms of E. coli Hsp70 (DnaK) and human Hsp70 proteins by small molecule inhibitors PET-16 and novolactone. Molecular dynamics simulations and binding free energy analysis were combined with network-based modeling of residue interactions and allosteric communications to systematically characterize and compare molecular signatures of the apo form, substrate-bound, and inhibitor-bound chaperone complexes. The results suggested a mechanism by which the allosteric inhibitors may leverage binding energy hotspots in the interaction networks to stabilize a specific conformational state and impair the interdomain allosteric control. Using the network-based centrality analysis and community detection, we demonstrated that substrate binding may strengthen the connectivity of local interaction communities, leading to a dense interaction network that can promote an efficient allosteric communication. In contrast, binding of PET-16 to DnaK may induce significant dynamic changes and lead to a fractured interaction network and impaired allosteric communications in the DnaK complex. By using a mechanistic-based analysis of distance fluctuation maps and allosteric propensities of protein residues, we determined that the allosteric network in the PET-16 complex may be small and localized due to the reduced communication and low cooperativity of the substrate binding loops, which may promote the higher rates of substrate dissociation and the decreased substrate affinity. In comparison with the significant effect of PET-16, binding of novolactone to HSPA1A may cause only moderate network changes and preserve allosteric

  6. Detection of molecular interactions

    DOEpatents

    Groves, John T.; Baksh, Michael M.; Jaros, Michal

    2012-02-14

    A method and assay are described for measuring the interaction between a ligand and an analyte. The assay can include a suspension of colloidal particles that are associated with a ligand of interest. The colloidal particles are maintained in the suspension at or near a phase transition state from a condensed phase to a dispersed phase. An analyte to be tested is then added to the suspension. If the analyte binds to the ligand, a phase change occurs to indicate that the binding was successful.

  7. Dynamic molecular crystals with switchable physical properties.

    PubMed

    Sato, Osamu

    2016-06-21

    The development of molecular materials whose physical properties can be controlled by external stimuli - such as light, electric field, temperature, and pressure - has recently attracted much attention owing to their potential applications in molecular devices. There are a number of ways to alter the physical properties of crystalline materials. These include the modulation of the spin and redox states of the crystal's components, or the incorporation within the crystalline lattice of tunable molecules that exhibit stimuli-induced changes in their molecular structure. A switching behaviour can also be induced by changing the molecular orientation of the crystal's components, even in cases where the overall molecular structure is not affected. Controlling intermolecular interactions within a molecular material is also an effective tool to modulate its physical properties. This Review discusses recent advances in the development of such stimuli-responsive, switchable crystalline compounds - referred to here as dynamic molecular crystals - and suggests how different approaches can serve to prepare functional materials. PMID:27325090

  8. Molecular dynamics investigation of the interaction of an edge dislocation with Frank loops in Fe-Ni10-Cr20 alloy

    NASA Astrophysics Data System (ADS)

    Baudouin, Jean-Baptiste; Nomoto, Akiyoshi; Perez, Michel; Monnet, Ghiath; Domain, Christophe

    2015-10-01

    The inhibition of dislocations motion by irradiation-induced defects, such as dislocation loops, is one of the main mechanisms of irradiation hardening of austenitic stainless steels. In this work, Molecular Dynamics (MD) simulations of interaction between an edge dislocation and Frank loops in Fe-Ni10-Cr20 ternary alloy mimicking austenitic stainless steels are carried out to investigate and model dislocation behavior. An empirical interatomic potential developed recently for a ternary FeNiCr system is used for the MD calculations. The interactions are calculated at different temperatures, loop orientations, loop size and solute atom configurations. The results show that the loop strength and the interaction processes depend on the solute atom configuration, the geometrical configurations between the dislocation and the loop and temperature. It is also demonstrated that a small Frank loop is not so weak an obstacle in the alloy. The interaction leads microstructural change such as loop shearing, loop unfaulting and loop absorption in the dislocation. In the former two cases, the loop remains after the interaction, however in some cases an absorption of the remaining loop by subsequent interactions with successive dislocations is observed.

  9. An image-based reaction field method for electrostatic interactions in molecular dynamics simulations of aqueous solutions

    NASA Astrophysics Data System (ADS)

    Lin, Yuchun; Baumketner, Andrij; Deng, Shaozhong; Xu, Zhenli; Jacobs, Donald; Cai, Wei

    2009-10-01

    In this paper, a new solvation model is proposed for simulations of biomolecules in aqueous solutions that combines the strengths of explicit and implicit solvent representations. Solute molecules are placed in a spherical cavity filled with explicit water, thus providing microscopic detail where it is most needed. Solvent outside of the cavity is modeled as a dielectric continuum whose effect on the solute is treated through the reaction field corrections. With this explicit/implicit model, the electrostatic potential represents a solute molecule in an infinite bath of solvent, thus avoiding unphysical interactions between periodic images of the solute commonly used in the lattice-sum explicit solvent simulations. For improved computational efficiency, our model employs an accurate and efficient multiple-image charge method to compute reaction fields together with the fast multipole method for the direct Coulomb interactions. To minimize the surface effects, periodic boundary conditions are employed for nonelectrostatic interactions. The proposed model is applied to study liquid water. The effect of model parameters, which include the size of the cavity, the number of image charges used to compute reaction field, and the thickness of the buffer layer, is investigated in comparison with the particle-mesh Ewald simulations as a reference. An optimal set of parameters is obtained that allows for a faithful representation of many structural, dielectric, and dynamic properties of the simulated water, while maintaining manageable computational cost. With controlled and adjustable accuracy of the multiple-image charge representation of the reaction field, it is concluded that the employed model achieves convergence with only one image charge in the case of pure water. Future applications to pKa calculations, conformational sampling of solvated biomolecules and electrolyte solutions are briefly discussed.

  10. Topology of molecular interaction networks.

    PubMed

    Winterbach, Wynand; Van Mieghem, Piet; Reinders, Marcel; Wang, Huijuan; de Ridder, Dick

    2013-01-01

    Molecular interactions are often represented as network models which have become the common language of many areas of biology. Graphs serve as convenient mathematical representations of network models and have themselves become objects of study. Their topology has been intensively researched over the last decade after evidence was found that they share underlying design principles with many other types of networks.Initial studies suggested that molecular interaction network topology is related to biological function and evolution. However, further whole-network analyses did not lead to a unified view on what this relation may look like, with conclusions highly dependent on the type of molecular interactions considered and the metrics used to study them. It is unclear whether global network topology drives function, as suggested by some researchers, or whether it is simply a byproduct of evolution or even an artefact of representing complex molecular interaction networks as graphs.Nevertheless, network biology has progressed significantly over the last years. We review the literature, focusing on two major developments. First, realizing that molecular interaction networks can be naturally decomposed into subsystems (such as modules and pathways), topology is increasingly studied locally rather than globally. Second, there is a move from a descriptive approach to a predictive one: rather than correlating biological network topology to generic properties such as robustness, it is used to predict specific functions or phenotypes.Taken together, this change in focus from globally descriptive to locally predictive points to new avenues of research. In particular, multi-scale approaches are developments promising to drive the study of molecular interaction networks further. PMID:24041013

  11. Topology of molecular interaction networks

    PubMed Central

    2013-01-01

    Molecular interactions are often represented as network models which have become the common language of many areas of biology. Graphs serve as convenient mathematical representations of network models and have themselves become objects of study. Their topology has been intensively researched over the last decade after evidence was found that they share underlying design principles with many other types of networks. Initial studies suggested that molecular interaction network topology is related to biological function and evolution. However, further whole-network analyses did not lead to a unified view on what this relation may look like, with conclusions highly dependent on the type of molecular interactions considered and the metrics used to study them. It is unclear whether global network topology drives function, as suggested by some researchers, or whether it is simply a byproduct of evolution or even an artefact of representing complex molecular interaction networks as graphs. Nevertheless, network biology has progressed significantly over the last years. We review the literature, focusing on two major developments. First, realizing that molecular interaction networks can be naturally decomposed into subsystems (such as modules and pathways), topology is increasingly studied locally rather than globally. Second, there is a move from a descriptive approach to a predictive one: rather than correlating biological network topology to generic properties such as robustness, it is used to predict specific functions or phenotypes. Taken together, this change in focus from globally descriptive to locally predictive points to new avenues of research. In particular, multi-scale approaches are developments promising to drive the study of molecular interaction networks further. PMID:24041013

  12. Statistical Estimation of the Protein-Ligand Binding Free Energy Based On Direct Protein-Ligand Interaction Obtained by Molecular Dynamics Simulation

    PubMed Central

    Fukunishi, Yoshifumi; Nakamura, Haruki

    2012-01-01

    We have developed a method for estimating protein-ligand binding free energy (ΔG) based on the direct protein-ligand interaction obtained by a molecular dynamics simulation. Using this method, we estimated the ΔG value statistically by the average values of the van der Waals and electrostatic interactions between each amino acid of the target protein and the ligand molecule. In addition, we introduced fluctuations in the accessible surface area (ASA) and dihedral angles of the protein-ligand complex system as the entropy terms of the ΔG estimation. The present method included the fluctuation term of structural change of the protein and the effective dielectric constant. We applied this method to 34 protein-ligand complex structures. As a result, the correlation coefficient between the experimental and calculated ΔG values was 0.81, and the average error of ΔG was 1.2 kcal/mol with the use of the fixed parameters. These results were obtained from a 2 nsec molecular dynamics simulation. PMID:24281257

  13. Structural insights into the interaction between molluscan hemocyanins and phenolic substrates: An in silico study using docking and molecular dynamics.

    PubMed

    Naresh, K N; Sreekumar, Arun; Rajan, S S

    2015-09-01

    Hemocyanin is a multimeric type-3 copper containing oxygen carrier protein that exhibits phenoloxidase-like activity and is found in selected species of arthropoda and mollusca. The phenoloxidase activity in the molluscan hemocyanins can be triggered by the proteolytic removal of the C-terminal β-rich sandwich domain of the protein or by the treatment with chemical agents like SDS, both of which enable active site access to the phenolic substrates. The mechanism by which SDS treatment enhances active site access to the substrates is however not well understood in molluscan hemocyanins. Here, using a combination of in silico molecular dynamics (MD) and docking studies on the crystal structure of Octopus dofleini hemocyanin (PDB code:1JS8), we demonstrate that the C-terminal β-domain of the protein plays a crucial role in regulating active site access to bulky phenolic substrates. Furthermore, MD simulation of hemocyanin in SDS revealed displacement of β-domain, enhanced active site access and a resulting increase in binding affinity for substrates. These observations were further validated by enzyme kinetics experiments. PMID:26300244

  14. Molecular photoionization dynamics

    SciTech Connect

    Dehmer, Joseph L.

    1982-05-01

    This program seeks to develop both physical insight and quantitative characterization of molecular photoionization processes. Progress is briefly described, and some publications resulting from the research are listed. (WHK)

  15. Methyl Radical in Clathrate Silica Voids. The Peculiar Physisorption Features of the Guest-Host Molecular Dynamics Interaction.

    PubMed

    Dmitriev, Yurij A; Buscarino, Gianpiero; Benetis, Nikolas P

    2016-08-11

    EPR line shape simulations of CH3/SiO2 clathrates and comparison to CH3/N2O and CH3/SiO2 experiments reveal the motional conditions of the CH3 radical up to the unusual regime of its stability, the high-temperature diffusional regime, at 300 K. In the low-temperature region, the CH3 in clathrates is found to rotate around the in-plane axes even at as low temperatures as 3.8 K. However, nonrotating methyls performing only libration about the C2-axes as well as around the C3-axis are also found, proving the existence of special sites in the clathrate voids that begin to accumulate a significant fraction of methyl radicals at temperatures below approximately 7 K. A distinctive feature in the spectrum anisotropy and line width temperature profiles is found nearby 25 K, which is interpreted as the radical physisorption inside the voids that occurs with the sample temperature lowering. The unusual increase of the CH3/SiO2 clathrate EPR spectral width with temperature over approximately 120 K has its origin in repeated angular momentum vector alterations due to frequent collisions with the clathrate void walls between periodical free rotation periods. This relaxation mechanism resembles to spin-rotation interaction known only for small molecular species in nonviscous fluids but unknown earlier for methyl hosted in solids. PMID:27405003

  16. Molecular dynamics of membrane proteins.

    SciTech Connect

    Woolf, Thomas B.; Crozier, Paul Stewart; Stevens, Mark Jackson

    2004-10-01

    Understanding the dynamics of the membrane protein rhodopsin will have broad implications for other membrane proteins and cellular signaling processes. Rhodopsin (Rho) is a light activated G-protein coupled receptor (GPCR). When activated by ligands, GPCRs bind and activate G-proteins residing within the cell and begin a signaling cascade that results in the cell's response to external stimuli. More than 50% of all current drugs are targeted toward G-proteins. Rho is the prototypical member of the class A GPCR superfamily. Understanding the activation of Rho and its interaction with its Gprotein can therefore lead to a wider understanding of the mechanisms of GPCR activation and G-protein activation. Understanding the dark to light transition of Rho is fully analogous to the general ligand binding and activation problem for GPCRs. This transition is dependent on the lipid environment. The effect of lipids on membrane protein activity in general has had little attention, but evidence is beginning to show a significant role for lipids in membrane protein activity. Using the LAMMPS program and simulation methods benchmarked under the IBIG program, we perform a variety of allatom molecular dynamics simulations of membrane proteins.

  17. 2010 Atomic & Molecular Interactions Gordon Research Conference

    SciTech Connect

    Todd Martinez

    2010-07-23

    The Atomic and Molecular Interactions Gordon Conferences is justifiably recognized for its broad scope, touching on areas ranging from fundamental gas phase and gas-condensed matter collision dynamics, to laser-molecule interactions, photophysics, and unimolecular decay processes. The meeting has traditionally involved scientists engaged in fundamental research in gas and condensed phases and those who apply these concepts to systems of practical chemical and physical interest. A key tradition in this meeting is the strong mixing of theory and experiment throughout. The program for 2010 conference continues these traditions. At the 2010 AMI GRC, there will be talks in 5 broadly defined and partially overlapping areas of intermolecular interactions and chemical dynamics: (1) Photoionization and Photoelectron Dynamics; (2) Quantum Control and Molecules in Strong Fields; (3) Photochemical Dynamics; (4) Complex Molecules and Condensed Phases; and (5) Clusters and Reaction Dynamics. These areas encompass many of the most productive and exciting areas of chemical physics, including both reactive and nonreactive processes, intermolecular and intramolecular energy transfer, and photodissociation and unimolecular processes. Gas phase dynamics, van der Waals and cluster studies, laser-matter interactions and multiple potential energy surface phenomena will all be discussed.

  18. Dynamic-domain-decomposition parallel molecular dynamics

    NASA Astrophysics Data System (ADS)

    Srinivasan, S. G.; Ashok, I.; Jônsson, Hannes; Kalonji, Gretchen; Zahorjan, John

    1997-05-01

    Parallel molecular dynamics with short-range forces can suffer from load-imbalance problems and attendant performance degradation due to density variations in the simulated system. In this paper, we describe an approach to dynamical load balancing, enabled by the Ādhāra runtime system. The domain assigned to each processor is automatically and dynamically resized so as to evenly distribute the molecular dynamics computations across all the processors. The algorithm was tested on an Intel Paragon parallel computer for two and three-dimensional Lennard-Jones systems containing 99 458 and 256000 atoms, respectively, and using up to 256 processors. In these benchmarks, the overhead for carrying out the load-balancing operations was found to be small and the total computation time was reduced by as much as 50%.

  19. An investigation on the interaction modes of a single-strand DNA aptamer and RBP4 protein: a molecular dynamic simulations approach.

    PubMed

    Torabi, Raheleh; Bagherzadeh, Kowsar; Ghourchian, Hedayatollah; Amanlou, Massoud

    2016-09-14

    Type two diabetes is one of the primary health issues threatening public well-being worldwide. One of the pre-diagnosis biomarkers of this disease, retinol binding protein 4 (RBP4), has been demonstrated to be detected with a 76-mer ssDNA aptamer instead of conventional antibodies. However, there is no structural information on the RBP4 binding aptamer (RBA) and the mechanism of its binding to RBP4 still remains unexplored. The objective of the present study is to achieve a better understanding of specific binding interactions of the target protein (RBP4) and RBA, employing Molecular Dynamics simulations (MDs) to provide detailed information on fluctuations, conformational changes, critical bases and effective forces to develop regulated aptamers to be employed in designing new aptamers for many useful recognition applications. RBA was designed according to its reported base pair sequence and secondary structure. The HADDOCK on line docking program was used to predict a suitable RBP4-RBA mode of interaction to start MDs with. MDs methodology was used to analyze the final complex stability and detect interacting residues. Eventually, we conclude that single strand located bases are the key components that conduct the intercalation phenomenon with big targets rather than those involving loops and folded motifs, to encompass targets and probably inhibit their activity. Also, UV-visible, circular dichroism and fluorescence spectroscopy measurements confirmed the interactions between RBA and RBP4 and RBP4-RBA complex formation. PMID:27511589

  20. Antimicrobial peptide dendrimer interacts with phosphocholine membranes in a fluidity dependent manner: A neutron reflection study combined with molecular dynamics simulations.

    PubMed

    Lind, T K; Darré, L; Domene, C; Urbanczyk-Lipkowska, Z; Cárdenas, M; Wacklin, H P

    2015-10-01

    The interaction mechanism of a novel amphiphilic antimicrobial peptide dendrimer, BALY, with model lipid bilayers was explored through a combination of neutron reflection and molecular dynamics simulations. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3-phos-phocholine (DPPC) lipid bilayers were examined at room temperature to extract information on the interaction of BALY with fluid and gel phases, respectively. Furthermore, a 1:4 mixture of POPC and DPPC was used as a model of a phase-separated membrane. Upon interaction with fluid membranes, BALY inserted in the distal leaflet and caused thinning and disordering of the headgroups. Membrane thinning and expansion of the lipid cross-sectional area were observed for gel phase membranes, also with limited insertion to the distal leaflet. However, dendrimer insertion through the entire lipid tail region was observed upon crossing the lipid phase transition temperature of DPPC and in phase separated membranes. The results show clear differences in the interaction mechanism of the dendrimer depending on the lipid membrane fluidity, and suggest a role for lipid phase separation in promoting its antimicrobial activity. PMID:26025586

  1. Intermolecular interactions of liquid dichloromethane and equilibrium properties of liquid{endash}vapor and liquid{endash}liquid interfaces: A molecular dynamics study

    SciTech Connect

    Dang, L.X.

    1999-05-01

    Extensive molecular dynamics simulations are carried out to study the molecular interactions, liquid states, and liquid/vapor properties of dichloromethane. The study is also extended to the equilibrium properties of the liquid/liquid interface of water-dichloromethane. The intermolecular interactions among water, dichloromethane, and water-dichloromethane are described using our polarizable potential models. The equilibrium properties of liquid dichloromethane, including the radial distribution functions, the intermolecular structural factor, the self-diffusion coefficient, and the dielectric constant, are evaluated. The dielectric constant is computed using Ewald summation techniques and the computed result compared reasonably well with the available experimental data. Properties such as surface tensions and density profiles of liquid/vapor dichloromethane are evaluated. We found that the computed surface tensions for several temperatures are in excellent agreement with experimental data. The computed density profile of the liquid/liquid interface of water-dichloromethane is averaged over 1 ns and we found the computed profile to be quite smooth and stable. The effect of polarization on the liquid/liquid interfacial equilibrium properties is evaluated by computing the dipole moments of water and dichloromethane molecules as a function of the distance normal to the interface. We found that these values deviated significantly from the simulations that are based on nonpolarizable potential models. We attribute these observations to the changes in the electric fields around the water and dichloromethane molecules near the interface. {copyright} {ital 1999 American Institute of Physics.}

  2. Multielectron effects in high harmonic generation in N2 and benzene: Simulation using a non-adiabatic quantum molecular dynamics approach for laser-molecule interactions

    NASA Astrophysics Data System (ADS)

    Dundas, Daniel

    2012-05-01

    A mixed quantum-classical approach is introduced which allows the dynamical response of molecules driven far from equilibrium to be modeled. This method is applied to the interaction of molecules with intense, short-duration laser pulses. The electronic response of the molecule is described using time-dependent density functional theory (TDDFT) and the resulting Kohn-Sham equations are solved numerically using finite difference techniques in conjunction with local and global adaptations of an underlying grid in curvilinear coordinates. Using this approach, simulations can be carried out for a wide range of molecules and both all-electron and pseudopotential calculations are possible. The approach is applied to the study of high harmonic generation in N2 and benzene using linearly polarized laser pulses and, to the best of our knowledge, the results for benzene represent the first TDDFT calculations of high harmonic generation in benzene using linearly polarized laser pulses. For N2 an enhancement of the cut-off harmonics is observed whenever the laser polarization is aligned perpendicular to the molecular axis. This enhancement is attributed to the symmetry properties of the Kohn-Sham orbital that responds predominantly to the pulse. In benzene we predict that a suppression in the cut-off harmonics occurs whenever the laser polarization is aligned parallel to the molecular plane. We attribute this suppression to the symmetry-induced response of the highest-occupied molecular orbital.

  3. Identification of amino acid residues of a designed ankyrin repeat protein potentially involved in intermolecular interactions with CD4: analysis by molecular dynamics simulations.

    PubMed

    Nimmanpipug, Piyarat; Khampa, Chalermpon; Lee, Vannajan Sanghiran; Nangola, Sawitree; Tayapiwatana, Chatchai

    2011-11-01

    We applied molecular dynamics simulations to investigate the binding properties of a designed ankyrin repeat protein, the DARPin-CD4 complex. DARPin 23.2 has been reported to disturb the human immunodeficiency virus (HIV) viral entry process by Schweizer et al. The protein docking simulation was analysed by comparing the specific ankyrin binder (DARPin 23.2) to an irrelevant control (2JAB) in forming a composite with CD4. To determine the binding free energy of both ankyrins, the MM/PBSA and MM/GBSA protocols were used. The free energy decomposition of both complexes were analysed to explore the role of certain amino acid residues in complex configuration. Interestingly, the molecular docking analysis of DARPin 23.2 revealed a similar CD4 interaction regarding the gp120 theoretical anchoring motif. In contrast, the binding of control ankyrin to CD4 occurred at a different location. This observation suggests that there is an advantage to the molecular modification of DARPin 23.2, an enhanced affinity for CD4. PMID:21962990

  4. Correlation between inter-spin interaction and molecular dynamics of organic radicals in organic 1D nanochannels

    SciTech Connect

    Kobayashi, Hirokazu

    2015-12-31

    One-dimensional (1D) molecular chains of 4-substituted-2,2,6,6-tetramethyl-1-piperidinyloxyl (4-X-TEMPO) radicals were constructed in the crystalline 1D nanochannels of 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) used as a template. The ESR spectra of CLPOT inclusion compounds (ICs) using 4-X-TEMPO were examined on the basis of spectral simulation using EasySpin program package for simulating and fitting ESR spectra. The ESR spectra of [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC were isotropic in the total range of temperatures. The peak-to-peak line width (ΔB{sub pp}) became monotonically narrower from 2.8 to 1.3 mT with increase in temperature in the range of 4.2–298 K. The effect of the rotational diffusion motion of TEMPO radicals in the CLPOT nanochannels for the inter-spin interaction of the [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC was found to be smaller than the case of [(TPP){sub 2}−(TEMPO){sub 1.0}] IC (TPP = tris(o-phenylenedioxy)cyclotriphosphazene) reported in our previous study. The ΔB{sub pp} of the [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC in the whole range of temperatures was much narrower than the estimation to be based on the Van Vleck’s formula for the second moment of the rigid lattice model where the electron spin can be considered as fixed; 11 mT of Gaussian line-width component. This suggests the possibility of exchange narrowing in the 1D organic-radical chains of the [(CLPOT){sub 2}-(TEMPO){sub 1.0}] IC. On the other hand, the ESR spectra of [(CLPOT){sub 2}-(MeO-TEMPO){sub 0.41}] IC (MeO-TEMPO = 4-methoxy-TEMPO) were reproduced by a superposition of major broad isotropic adsorption line and minor temperature-dependent modulated triplet component. This suggests that the IC has the part of 1D organic-radical chains and MeO-TEMPO molecules isolated in the CLPOT nanochannels.

  5. Correlation between inter-spin interaction and molecular dynamics of organic radicals in organic 1D nanochannels

    NASA Astrophysics Data System (ADS)

    Kobayashi, Hirokazu

    2015-12-01

    One-dimensional (1D) molecular chains of 4-substituted-2,2,6,6-tetramethyl-1-piperidinyloxyl (4-X-TEMPO) radicals were constructed in the crystalline 1D nanochannels of 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) used as a template. The ESR spectra of CLPOT inclusion compounds (ICs) using 4-X-TEMPO were examined on the basis of spectral simulation using EasySpin program package for simulating and fitting ESR spectra. The ESR spectra of [(CLPOT)2-(TEMPO)1.0] IC were isotropic in the total range of temperatures. The peak-to-peak line width (ΔBpp) became monotonically narrower from 2.8 to 1.3 mT with increase in temperature in the range of 4.2-298 K. The effect of the rotational diffusion motion of TEMPO radicals in the CLPOT nanochannels for the inter-spin interaction of the [(CLPOT)2-(TEMPO)1.0] IC was found to be smaller than the case of [(TPP)2-(TEMPO)1.0] IC (TPP = tris(o-phenylenedioxy)cyclotriphosphazene) reported in our previous study. The ΔBpp of the [(CLPOT)2-(TEMPO)1.0] IC in the whole range of temperatures was much narrower than the estimation to be based on the Van Vleck's formula for the second moment of the rigid lattice model where the electron spin can be considered as fixed; 11 mT of Gaussian line-width component. This suggests the possibility of exchange narrowing in the 1D organic-radical chains of the [(CLPOT)2-(TEMPO)1.0] IC. On the other hand, the ESR spectra of [(CLPOT)2-(MeO-TEMPO)0.41] IC (MeO-TEMPO = 4-methoxy-TEMPO) were reproduced by a superposition of major broad isotropic adsorption line and minor temperature-dependent modulated triplet component. This suggests that the IC has the part of 1D organic-radical chains and MeO-TEMPO molecules isolated in the CLPOT nanochannels.

  6. Molecular dynamics and protein function

    PubMed Central

    Karplus, M.; Kuriyan, J.

    2005-01-01

    A fundamental appreciation for how biological macromolecules work requires knowledge of structure and dynamics. Molecular dynamics simulations provide powerful tools for the exploration of the conformational energy landscape accessible to these molecules, and the rapid increase in computational power coupled with improvements in methodology makes this an exciting time for the application of simulation to structural biology. In this Perspective we survey two areas, protein folding and enzymatic catalysis, in which simulations have contributed to a general understanding of mechanism. We also describe results for the F1 ATPase molecular motor and the Src family of signaling proteins as examples of applications of simulations to specific biological systems. PMID:15870208

  7. A sampling of molecular dynamics

    NASA Astrophysics Data System (ADS)

    Sindhikara, Daniel Jon

    The sheer vastness of the number of computations required to simulate a biological molecule puts incredible pressure on algorithms to be efficient while maintaining sufficient accuracy. This dissertation summarizes various projects whose purposes address the large span of types of problems in molecular dynamics simulations of biological systems including: increasing efficiency, measuring convergence, avoiding pitfalls, and an application and analysis of a biological system. Chapters 3 and 4 deal with an enhanced sampling algorithm called "replica exchange molecular dynamics" which is designed to speed-up molecular dynamics simulations. The optimization of a key parameter of these simulations is analyzed. In these successive projects, it was found conclusively that maximizing "exchange attempt frequency" is the most efficient way to run a replica exchange molecular dynamics simulation. Chapter 5 describes an enhanced metric for convergence in parallel simulations called the normalized ergodic measure. The metric is applied to several properties for several replica exchange simulations. Advantages of this metric over other methods are described. Chapter 6 describes the implementation and optimization of an enhanced sampling algorithm similar to replica exchange molecular dynamics called multicanonical algorithm replica exchange molecular dynamics. The algorithm was implemented into a biomolecular simulation suite called AMBER. Additionally several parameters were analyzed and optimized. In Chapter 7, a pitfall in molecular dynamics is observed in biological systems that is caused by negligent use of a simulation's "thermostat". It was found that if the same pseudorandom number seed were used for multiple systems, they eventually synchronize. In this project, synchronization was observed in biological molecules. Various negative effects including corruption of data are pointed out. Chapter 8 describes molecular dynamics simulation of NikR, a homotetrameric nickel

  8. Gas Phase Molecular Dynamics

    SciTech Connect

    Hall, G.E.; Prrese, J.M.; Sears, T.J.; Weston, R.E.

    1999-05-21

    The goal of this research is the understanding of elementary chemical and physical processes important in the combustion of fossil fuels. Interest centers on reactions involving short-lived chemical intermediates and their properties. High-resolution high-sensitivity laser absorption methods are augmented by high temperature flow-tube reaction kinetics studies with mass spectrometric sampling. These experiments provide information on the energy levels, structures and reactivity of molecular flee radical species and, in turn, provide new tools for the study of energy flow and chemical bond cleavage in the radicals in chemical systems. The experimental work is supported by theoretical and computational work using time-dependent quantum wavepacket calculations that provide insights into energy flow between the vibrational modes of the molecule.

  9. Integration methods for molecular dynamics

    SciTech Connect

    Leimkuhler, B.J.; Reich, S.; Skeel, R.D.

    1996-12-31

    Classical molecular dynamics simulation of a macromolecule requires the use of an efficient time-stepping scheme that can faithfully approximate the dynamics over many thousands of timesteps. Because these problems are highly nonlinear, accurate approximation of a particular solution trajectory on meaningful time intervals is neither obtainable nor desired, but some restrictions, such as symplecticness, can be imposed on the discretization which tend to imply good long term behavior. The presence of a variety of types and strengths of interatom potentials in standard molecular models places severe restrictions on the timestep for numerical integration used in explicit integration schemes, so much recent research has concentrated on the search for alternatives that possess (1) proper dynamical properties, and (2) a relative insensitivity to the fastest components of the dynamics. We survey several recent approaches. 48 refs., 2 figs.

  10. Transcript dynamics at early stages of molecular interactions of MYMIV with resistant and susceptible genotypes of the leguminous host, Vigna mungo.

    PubMed

    Kundu, Anirban; Patel, Anju; Paul, Sujay; Pal, Amita

    2015-01-01

    Initial phases of the MYMIV-Vigna mungo interaction is crucial in determining the infection phenotype upon challenging with the virus. During incompatible interaction, the plant deploys multiple stratagems that include extensive transcriptional alterations defying the virulence factors of the pathogen. Such molecular events are not frequently addressed by genomic tools. In order to obtain a critical insight to unravel how V. mungo respond to Mungbean yellow mosaic India virus (MYMIV), we have employed the PCR based suppression subtractive hybridization technique to identify genes that exhibit altered expressions. Dynamics of 345 candidate genes are illustrated that differentially expressed either in compatible or incompatible reactions and their possible biological and cellular functions are predicted. The MYMIV-induced physiological aspects of the resistant host include reactive oxygen species generation, induction of Ca2+ mediated signaling, enhanced expression of transcripts involved in phenylpropanoid and ubiquitin-proteasomal pathways; all these together confer resistance against the invader. Elicitation of genes implicated in salicylic acid (SA) pathway suggests that immune response is under the regulation of SA signaling. A significant fraction of modulated transcripts are of unknown function indicating participation of novel candidate genes in restricting this viral pathogen. Susceptibility on the other hand, as exhibited by V. mungo Cv. T9 is perhaps due to the poor execution of these transcript modulation exhibiting remarkable repression of photosynthesis related genes resulting in chlorosis of leaves followed by penalty in crop yield. Thus, the present findings revealed an insight on the molecular warfare during host-virus interaction suggesting plausible signaling mechanisms and key biochemical pathways overriding MYMIV invasion in resistant genotype of V. mungo. In addition to inflate the existing knowledge base, the genomic resources identified in

  11. Transcript Dynamics at Early Stages of Molecular Interactions of MYMIV with Resistant and Susceptible Genotypes of the Leguminous Host, Vigna mungo

    PubMed Central

    Kundu, Anirban; Patel, Anju; Paul, Sujay; Pal, Amita

    2015-01-01

    Initial phases of the MYMIV- Vigna mungo interaction is crucial in determining the infection phenotype upon challenging with the virus. During incompatible interaction, the plant deploys multiple stratagems that include extensive transcriptional alterations defying the virulence factors of the pathogen. Such molecular events are not frequently addressed by genomic tools. In order to obtain a critical insight to unravel how V. mungo respond to Mungbean yellow mosaic India virus (MYMIV), we have employed the PCR based suppression subtractive hybridization technique to identify genes that exhibit altered expressions. Dynamics of 345 candidate genes are illustrated that differentially expressed either in compatible or incompatible reactions and their possible biological and cellular functions are predicted. The MYMIV-induced physiological aspects of the resistant host include reactive oxygen species generation, induction of Ca2+ mediated signaling, enhanced expression of transcripts involved in phenylpropanoid and ubiquitin-proteasomal pathways; all these together confer resistance against the invader. Elicitation of genes implicated in salicylic acid (SA) pathway suggests that immune response is under the regulation of SA signaling. A significant fraction of modulated transcripts are of unknown function indicating participation of novel candidate genes in restricting this viral pathogen. Susceptibility on the other hand, as exhibited by V. mungo Cv. T9 is perhaps due to the poor execution of these transcript modulation exhibiting remarkable repression of photosynthesis related genes resulting in chlorosis of leaves followed by penalty in crop yield. Thus, the present findings revealed an insight on the molecular warfare during host-virus interaction suggesting plausible signaling mechanisms and key biochemical pathways overriding MYMIV invasion in resistant genotype of V. mungo. In addition to inflate the existing knowledge base, the genomic resources identified in

  12. Development of hardware accelerator for molecular dynamics simulations: a computation board that calculates nonbonded interactions in cooperation with fast multipole method.

    PubMed

    Amisaki, Takashi; Toyoda, Shinjiro; Miyagawa, Hiroh; Kitamura, Kunihiro

    2003-04-15

    Evaluation of long-range Coulombic interactions still represents a bottleneck in the molecular dynamics (MD) simulations of biological macromolecules. Despite the advent of sophisticated fast algorithms, such as the fast multipole method (FMM), accurate simulations still demand a great amount of computation time due to the accuracy/speed trade-off inherently involved in these algorithms. Unless higher order multipole expansions, which are extremely expensive to evaluate, are employed, a large amount of the execution time is still spent in directly calculating particle-particle interactions within the nearby region of each particle. To reduce this execution time for pair interactions, we developed a computation unit (board), called MD-Engine II, that calculates nonbonded pairwise interactions using a specially designed hardware. Four custom arithmetic-processors and a processor for memory manipulation ("particle processor") are mounted on the computation board. The arithmetic processors are responsible for calculation of the pair interactions. The particle processor plays a central role in realizing efficient cooperation with the FMM. The results of a series of 50-ps MD simulations of a protein-water system (50,764 atoms) indicated that a more stringent setting of accuracy in FMM computation, compared with those previously reported, was required for accurate simulations over long time periods. Such a level of accuracy was efficiently achieved using the cooperative calculations of the FMM and MD-Engine II. On an Alpha 21264 PC, the FMM computation at a moderate but tolerable level of accuracy was accelerated by a factor of 16.0 using three boards. At a high level of accuracy, the cooperative calculation achieved a 22.7-fold acceleration over the corresponding conventional FMM calculation. In the cooperative calculations of the FMM and MD-Engine II, it was possible to achieve more accurate computation at a comparable execution time by incorporating larger nearby

  13. Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations.

    PubMed

    Wang, Bo; Li, Liwei; Hurley, Thomas D; Meroueh, Samy O

    2013-10-28

    End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed understanding of molecular recognition in protein-ligand interactions. The binding free energy can be used to rank-order protein-ligand structures in virtual screening for compound or target identification. Here, we carry out free energy calculations for a diverse set of 11 proteins bound to 14 small molecules using extensive explicit-solvent MD simulations. The structure of these complexes was previously solved by crystallography and their binding studied with isothermal titration calorimetry (ITC) data enabling direct comparison to the MM-GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations reproduced the ITC free energy within 1 kcal·mol(-1) highlighting the challenges in reproducing the absolute free energy from end-point free energy calculations. MM-GBSA exhibited better rank-ordering with a Spearman ρ of 0.68 compared to 0.40 for MM-PBSA with dielectric constant (ε = 1). An increase in ε resulted in significantly better rank-ordering for MM-PBSA (ρ = 0.91 for ε = 10), but larger ε significantly reduced the contributions of electrostatics, suggesting that the improvement is due to the nonpolar and entropy components, rather than a better representation of the electrostatics. The SVRKB scoring function applied to MD snapshots resulted in excellent rank-ordering (ρ = 0.81). Calculations of the configurational entropy using normal-mode analysis led to free energies that correlated significantly better to the ITC free energy than the MD-based quasi-harmonic approach, but the computed entropies showed no correlation with the ITC entropy. When the adaptation energy is taken into consideration by running separate simulations for complex, apo, and ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the individual free energies, but remarkably good rank-ordering is observed (ρ = 0.89). Interestingly, filtering MD snapshots by prescoring

  14. Molecular Dynamics Simulations of Graphene Oxide Frameworks

    SciTech Connect

    Zhu, Pan; Sumpter, Bobby G; Meunier, V.; Nicolai, Adrien

    2013-01-01

    We use quantum mechanical calculations to develop a full set of force field parameters in order to perform molecular dynamics simulations to understand and optimize the molecular storage properties inside Graphene Oxide Frameworks (GOFs). A set of boron-related parameters for commonly used empirical force fields is determined to describe the non-bonded and bonded interactions between linear boronic acid linkers and graphene sheets of GOF materials. The transferability of the parameters is discussed and their validity is quantified by comparing quantum mechanical and molecular mechanical structural and vibrational properties. The application of the model to the dynamics of water inside the GOFs reveals significant variations in structural flexibility of GOF depending on the linker density, which is shown to be usable as a tuning parameter for desired diffusion properties.

  15. Dynamical interactions of galaxy pairs

    NASA Technical Reports Server (NTRS)

    Athanassoula, E.

    1990-01-01

    Here the author briefly reviews the dynamics of sinking satellites and the effect of companions on elliptical galaxies. The author then discusses recent work on interacting disk systems, and finally focuses on a favorite interacting pair, NGC 5194/5195.

  16. Atomistic mechanism of polyphenol amyloid aggregation inhibitors: molecular dynamics study of Curcumin, Exifone, and Myricetin interaction with the segment of tau peptide oligomer.

    PubMed

    Berhanu, Workalemahu M; Masunov, Artëm E

    2015-01-01

    Amyloid fibrils are highly ordered protein aggregates associated with many diseases affecting millions of people worldwide. Polyphenols such as Curcumin, Exifone, and Myricetin exhibit modest inhibition toward fibril formation of tau peptide which is associated with Alzheimer's disease. However, the molecular mechanisms of this inhibition remain elusive. We investigated the binding of three polyphenol molecules to the protofibrils of an amyloidogenic fragment VQIVYK of tau peptide by molecular dynamics simulations in explicit solvent. We find that polyphenols induce conformational changes in the oligomer aggregate. These changes disrupt the amyloid H bonding, perturbing the aggregate. While the structural evolution of the control oligomer with no ligand is limited to the twisting of the β-sheets without their disassembly, the presence of polyphenol molecule pushes the β-sheets apart, and leads to a loosely packed structure where two of four β-sheets dissociate in each of the three cases considered here. The H-bonding capacity of polyphenols is responsible for the observed behavior. The calculated binding free energies and its individual components enabled better understanding of the binding. Results indicated that the contribution from Van der Waals interactions is more significant than electrostatic contribution to the binding. The findings from this study are expected to assist in the development of aggregation inhibitors. Significant binding between polyphenols and aggregate oligomer identified in our simulations confirms the previous experimental observations in which polyphenols refold the tau peptide without forming covalent bonds. PMID:25093402

  17. Molecular dynamics investigation of nanoscale cavitation dynamics

    NASA Astrophysics Data System (ADS)

    Sasikumar, Kiran; Keblinski, Pawel

    2014-12-01

    We use molecular dynamics simulations to investigate the cavitation dynamics around intensely heated solid nanoparticles immersed in a model Lennard-Jones fluid. Specifically, we study the temporal evolution of vapor nanobubbles that form around the solid nanoparticles heated over ps time scale and provide a detail description of the following vapor formation and collapse. For 8 nm diameter nanoparticles we observe the formation of vapor bubbles when the liquid temperature 0.5-1 nm away from the nanoparticle surface reaches ˜90% of the critical temperature, which is consistent with the onset of spinodal decomposition. The peak heat flux from the hot solid to the surrounding liquid at the bubble formation threshold is ˜20 times higher than the corresponding steady state critical heat flux. Detailed analysis of the bubble dynamics indicates adiabatic formation followed by an isothermal final stage of growth and isothermal collapse.

  18. Ab initio molecular dynamics simulations of ion–solid interactions in Gd2Zr2O7 and Gd2Ti2O7

    SciTech Connect

    Wang, X. J.; Xiao, Haiyan Y.; Zu, Xiaotao; Zhang, Yanwen; Weber, William J.

    2012-12-21

    The development of the ab initio molecular dynamics (AIMD) method has made it a powerful tool in describing ion–solid interactions in materials, with the determination of threshold displacement energies with ab initio accuracy, and prediction of a new mechanism for defect generation and new defective states that are different from classical molecular dynamics (MD) simulations. In the present work, this method is employed to study the low energy recoil events in Gd2Zr2O7 and Gd2Ti2O7. The weighted average threshold displacement energies in Gd2Zr2O7 are determined to be 38.8 eV for Gd, 41.4 eV for Zr, 18.6 eV for O48f, and 15.6 eV for O8b, which are smaller than the respective values of 41.8, >53.8, 22.6 and 16.2 eV in Gd2Ti2O7. It reveals that all the ions in Gd2Zr2O7 are more easily displaced than those in Gd2Ti2O7, and anion order–disorder is more likely to be involved in the displacement events than cation disordering. The average charge transfer from the primary knock-on atom to its neighbors is estimated to be [similar]0.15, [similar]0.11 to 0.27 and [similar]0.1 to 0.13 |e| for Gd, Zr (or Ti), and O, respectively. Neglecting the charge transfer in the interatomic potentials may result in the larger threshold displacement energies in classical MD.

  19. Ab initio molecular dynamics simulations of ion-solid interactions in Gd2Zr2O7 and Gd2Ti2O7

    SciTech Connect

    Wang, X J; Xiao, Haiyan; Zu, X T; Zhang, Yanwen; Weber, William J

    2013-01-01

    The development of ab initio molecular dynamics (AIMD) method has made it a powerful tool in describing ion-solid interactions in materials, with identification determination of threshold displacement energies with ab initio accuracy, and prediction of new mechanism for defect generation and new defective states that are different from classical molecular dynamics (MD) simulations. In the present work, this method is employed to study the low energy recoil events in Gd2Zr2O7 and Gd2Ti2O7. The weighted average threshold displacement energies in Gd2Zr2O7 are determined to be 38.8 eV for Gd, 41.4 eV for Zr, 18.6 eV for O48f, and 15.6 eV for O8b, which are smaller than the respective values of 41.8, >53.8, 22.6 and 16.2 eV in Gd2Ti2O7. It reveals that all the ions in Gd2Zr2O7 are more easily displaced than those in Gd2Ti2O7, and anion order-disorder are more likely to be involved in the displacement events than cation disordering. The average charge transfer from the primary knock-on atom to its neighbors is estimated to be ~0.15, ~0.11-0.27 and ~0.1-0.13 |e| for Gd, Zr (or Ti), and O, respectively. Negligence of the charge transfer in the interatomic potentials may result in the larger threshold displacement energies in classical MD.

  20. Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80.

    PubMed

    Mobasheri, Meysam; Attar, Hossein; Rezayat Sorkhabadi, Seyed Mehdi; Khamesipour, Ali; Jaafari, Mahmoud Reza

    2015-01-01

    Amphotericin B (AmB) and Nystatin (Nys) are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, using a coarse-grained (CG) molecular dynamics (MD) simulation approach, we investigated the interaction of AmB and Nys with Polysorbate 80 (P80) to gain insight into the behavior of these polyene antibiotics (PAs) in nanomicellar solution and derive potential implications for their formulation development. While the encapsulation process was predominantly governed by hydrophobic forces, the dynamics, hydration, localization, orientation, and solvation of PAs in the micelle were largely controlled by hydrophilic interactions. Simulation results rationalized the experimentally observed capability of P80 in solubilizing PAs by indicating (i) the dominant kinetics of drugs encapsulation over self-association; (ii) significantly lower hydration of the drugs at encapsulated state compared with aggregated state; (iii) monomeric solubilization of the drugs; (iv) contribution of drug-micelle interactions to the solubilization; (v) suppressed diffusivity of the encapsulated drugs; (vi) high loading capacity of the micelle; and (vii) the structural robustness of the micelle against drug loading. Supported from the experimental data, our simulations determined the preferred location of PAs to be the core-shell interface at the relatively shallow depth of 75% of micelle radius. Deeper penetration of PAs was impeded by the synergistic effects of (i) limited diffusion of water; and (ii) perpendicular orientation of these drug molecules with respect to the micelle radius. PAs were solvated almost exclusively in the aqueous poly-oxyethylene (POE) medium due to the distance-related lack of interaction with the core, explaining the documented insensitivity of Nys solubilization to drug

  1. Structure, Dynamics, and Interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 Examined by Molecular Modeling, Simulation, and Electrostatic Studies

    PubMed Central

    Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

    2015-01-01

    The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269–330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95–113, 146–157, and 197–226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB

  2. Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

    PubMed

    Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

    2015-01-01

    The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB. PMID

  3. Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt(II) and Pd(II) complexes of glycine derivatives with calf thymus DNA.

    PubMed

    Eslami Moghadam, Mahboube; Saidifar, Maryam; Divsalar, Adeleh; Mansouri-Torshizi, Hassan; Saboury, Ali Akbar; Farhangian, Hossein; Ghadamgahi, Maryam

    2016-01-01

    Some amino acid derivatives, such as R-glycine, have been synthesized together with their full spectroscopic characterization. The sodium salts of these bidentate amino acid ligands have been interacted with [M(bpy)(H2O)2](NO3)2 giving the corresponding some new complexes with formula [M(bpy)(R-gly)]NO3 (where M is Pt(II) or Pd(II), bpy is 2,2'-bipyridine and R-gly is butyl-, hexyl- and octyl-glycine). Due to less solubility of octyl derivatives, the biological activities of butyl and hexyl derivatives have been tested against chronic myelogenous leukemia cell line, K562. The interaction of these complexes with highly polymerized calf thymus DNA has been extensively studied by means of electronic absorption, fluorescence and other measurements. The experimental results suggest that these complexes positive cooperatively bind to DNA presumably via groove binding. Molecular dynamic results show that the DNA structure is largely maintained its native structure in hexylglycine derivative-water mixtures and at lower temperatures. The simulation data indicates that the more destabilizing effect of butylglycine is induced by preferential accumulation of these molecules around the DNA and due to their more negative free energy of binding via groove binding. PMID:25734364

  4. The role of side-chain interactions in the early steps of aggregation: Molecular dynamics simulations of an amyloid-forming peptide from the yeast prion Sup35

    NASA Astrophysics Data System (ADS)

    Gsponer, Jörg; Haberthür, Urs; Caflisch, Amedeo

    2003-04-01

    Understanding the early steps of aggregation at atomic detail might be crucial for the rational design of therapeutics preventing diseases associated with amyloid deposits. In this paper, aggregation of the heptapeptide GNNQQNY, from the N-terminal prion-determining domain of the yeast protein Sup35, was studied by 20 molecular dynamics runs for a total simulation time of 20 μs. The simulations generate in-register parallel packing of GNNQQNY -strands that is consistent with x-ray diffraction and Fourier transform infrared data. The statistically preferred aggregation pathway does not correspond to a purely downhill profile of the energy surface because of the presence of enthalpic barriers that originate from out-of-register interactions. The parallel -sheet arrangement is favored over the antiparallel because of side-chain contacts; in particular, stacking interactions of the tyrosine rings and hydrogen bonds between amide groups. No ordered aggregation was found in control simulations with the mutant sequence SQNGNQQRG in accord with experimental data and the strong sequence dependence of aggregation.

  5. The dopamine D2 receptor dimer and its interaction with homobivalent antagonists: homology modeling, docking and molecular dynamics.

    PubMed

    Kaczor, Agnieszka A; Jörg, Manuela; Capuano, Ben

    2016-09-01

    In order to apply structure-based drug design techniques to G protein-coupled receptor complexes, it is essential to model their 3D structure and to identify regions that are suitable for selective drug binding. For this purpose, we have developed and tested a multi-component protocol to model the inactive conformation of the dopamine D2 receptor dimer, suitable for interaction with homobivalent antagonists. Our approach was based on protein-protein docking, applying the Rosetta software to obtain populations of dimers as present in membranes with all the main possible interfaces. Consensus scoring based on the values and frequencies of best interfaces regarding four scoring parameters, Rosetta interface score, interface area, free energy of binding and energy of hydrogen bond interactions indicated that the best scored dimer model possesses a TM4-TM5-TM7-TM1 interface, which is in agreement with experimental data. This model was used to study interactions of the previously published dopamine D2 receptor homobivalent antagonists based on clozapine,1,4-disubstituted aromatic piperidines/piperazines and arylamidoalkyl substituted phenylpiperazine pharmacophores. It was found that the homobivalent antagonists stabilize the receptor-inactive conformation by maintaining the ionic lock interaction, and change the dimer interface by disrupting a set of hydrogen bonds and maintaining water- and ligand-mediated hydrogen bonds in the extracellular and intracellular part of the interface. Graphical Abstract Structure of the final model of the dopamine D2 receptor homodimer, indicating the distancebetween Tyr37 and Tyr 5.42 in the apo form (left) and in the complex with the ligand (right). PMID:27491852

  6. Stochastic Event-Driven Molecular Dynamics

    SciTech Connect

    Donev, Aleksandar Garcia, Alejandro L.; Alder, Berni J.

    2008-02-01

    A novel Stochastic Event-Driven Molecular Dynamics (SEDMD) algorithm is developed for the simulation of polymer chains suspended in a solvent. SEDMD combines event-driven molecular dynamics (EDMD) with the Direct Simulation Monte Carlo (DSMC) method. The polymers are represented as chains of hard-spheres tethered by square wells and interact with the solvent particles with hard-core potentials. The algorithm uses EDMD for the simulation of the polymer chain and the interactions between the chain beads and the surrounding solvent particles. The interactions between the solvent particles themselves are not treated deterministically as in EDMD, rather, the momentum and energy exchange in the solvent is determined stochastically using DSMC. The coupling between the solvent and the solute is consistently represented at the particle level retaining hydrodynamic interactions and thermodynamic fluctuations. However, unlike full MD simulations of both the solvent and the solute, in SEDMD the spatial structure of the solvent is ignored. The SEDMD algorithm is described in detail and applied to the study of the dynamics of a polymer chain tethered to a hard-wall subjected to uniform shear. SEDMD closely reproduces results obtained using traditional EDMD simulations with two orders of magnitude greater efficiency. Results question the existence of periodic (cycling) motion of the polymer chain.

  7. Dynamic fracture toughness determined using molecular dynamics

    SciTech Connect

    Swadener, J. G.; Baskes, M. I.; Nastasi, Michael Anthony,

    2004-01-01

    Molecular dynamics (MD) simulations of fracture in crystalline silicon are conducted in order to determine the dynamic fracture toughness. The MD simulations show how the potential energy released during fracture is partitioned into surface energy, energy stored in defects and kinetic energy. First, the MD fracture simulations are shown to produce brittle fracture and be in reasonable agreement with experimental results. Then dynamic hcture toughness is calculated as the sum of the surface energy and the energy stored as defects directly from the MD models. Models oriented to produce fracture on either (111) or (101) planes are used. For the (101) fracture orientation, equilibrium crack speeds of greater than 80% of the Rayleigh wave speed are obtained. Crack speeds initially show a steep increase with increasing energy release rate followed by a much more gradual increase. No plateau in crack speed is observed for static energy release rates up to 20 J/m{sup 2}. At the point where the change in crack speed behavior occur, the dynamic fracture toughness (J{sub d}) is still within 10% of two times the surface energy (2{gamma}{sub 0}) and changing very slowly. From these MD simulations, it appears that the change in crack speed behavior is due to a change in the kinetic energy generation during dynamic fracture. In addition, MD simulations of facture in silicon with defects were conducted. The addition of defects increases the inelastic dissipation and the energy stored in defects.

  8. Fiftieth anniversary of molecular dynamics

    NASA Astrophysics Data System (ADS)

    Melker, Alexander I.

    2007-04-01

    The history of computer application in physics for solving nonlinear problems is considered. Examples from different branches of condensed matter physics (nonlinear vibrations of anharmonic chains of atoms, dynamics of radiation damage of crystals, deformation and fracture of crystals) are given. A new line of investigation and the results obtained in the field of computer simulation of physical processes realized in the department of metal physics and computer technologies in materials science are considered. This line incorporates both a study of self-organization and properties of new materials (fullerenes, carbon nanotubes) and biological objects by molecular dynamics technique as well as the development of new computer simulation methods.

  9. Dynamic molecules: molecular dynamics for everyone. An internet-based access to molecular dynamic simulations: basic concepts.

    PubMed

    Frank, Martin; Gutbrod, Peter; Hassayoun, Chokri; von Der Lieth, Claus-W

    2003-10-01

    Molecular dynamics is a rapidly developing field of science and has become an established tool for studying the dynamic behavior of biomolecules. Although several high quality programs for performing molecular dynamic simulations are freely available, only well-trained scientists are currently able to make use of the broad scientific potential that molecular dynamic simulations offer to gain insight into structural questions at an atomic level. The "Dynamic Molecules" approach is the first internet portal that provides an interactive access to set up, perform and analyze molecular dynamic simulations. It is completely based on standard web technologies and uses only publicly available software. The aim is to open molecular dynamics techniques to a broader range of users including undergraduate students, teachers and scientists outside the bioinformatics field. The time-limiting factors are the availability of free capacity on the computing server to run the simulations and the time required to transport the history file through the internet for the animation mode. The interactive access mode of the portal is acceptable for animations of molecules having up to about 500 atoms. PMID:12908101

  10. Available Instruments for Analyzing Molecular Dynamics Trajectories

    PubMed Central

    Likhachev, I. V.; Balabaev, N. K.; Galzitskaya, O. V.

    2016-01-01

    Molecular dynamics trajectories are the result of molecular dynamics simulations. Trajectories are sequential snapshots of simulated molecular system which represents atomic coordinates at specific time periods. Based on the definition, in a text format trajectory files are characterized by their simplicity and uselessness. To obtain information from such files, special programs and information processing techniques are applied: from molecular dynamics animation to finding characteristics along the trajectory (versus time). In this review, we describe different programs for processing molecular dynamics trajectories. The performance of these programs, usefulness for analyses of molecular dynamics trajectories, strong and weak aspects are discussed. PMID:27053964