X-ray Intermolecular Structure Factor (XISF): separation of intra- and intermolecular interactions from total X-ray scattering data

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

Mou, Q.; Benmore, C. J.; Yarger, J. L.

2015-06-01

XISF is a MATLAB program developed to separate intermolecular structure factors from total X-ray scattering structure factors for molecular liquids and amorphous solids. The program is built on a trust-region-reflective optimization routine with the r.m.s. deviations of atoms physically constrained. XISF has been optimized for performance and can separate intermolecular structure factors of complex molecules.

X-ray Intermolecular Structure Factor ( XISF ): separation of intra- and intermolecular interactions from total X-ray scattering data

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

Mou, Q.; Benmore, C. J.; Yarger, J. L.

2015-05-09

XISFis a MATLAB program developed to separate intermolecular structure factors from total X-ray scattering structure factors for molecular liquids and amorphous solids. The program is built on a trust-region-reflective optimization routine with the r.m.s. deviations of atoms physically constrained.XISFhas been optimized for performance and can separate intermolecular structure factors of complex molecules.

Simultaneous optimization of biomolecular energy function on features from small molecules and macromolecules

PubMed Central

Park, Hahnbeom; Bradley, Philip; Greisen, Per; Liu, Yuan; Mulligan, Vikram Khipple; Kim, David E.; Baker, David; DiMaio, Frank

2017-01-01

Most biomolecular modeling energy functions for structure prediction, sequence design, and molecular docking, have been parameterized using existing macromolecular structural data; this contrasts molecular mechanics force fields which are largely optimized using small-molecule data. In this study, we describe an integrated method that enables optimization of a biomolecular modeling energy function simultaneously against small-molecule thermodynamic data and high-resolution macromolecular structural data. We use this approach to develop a next-generation Rosetta energy function that utilizes a new anisotropic implicit solvation model, and an improved electrostatics and Lennard-Jones model, illustrating how energy functions can be considerably improved in their ability to describe large-scale energy landscapes by incorporating both small-molecule and macromolecule data. The energy function improves performance in a wide range of protein structure prediction challenges, including monomeric structure prediction, protein-protein and protein-ligand docking, protein sequence design, and prediction of the free energy changes by mutation, while reasonably recapitulating small-molecule thermodynamic properties. PMID:27766851

Molecular beacon sequence design algorithm.

PubMed

Monroe, W Todd; Haselton, Frederick R

2003-01-01

A method based on Web-based tools is presented to design optimally functioning molecular beacons. Molecular beacons, fluorogenic hybridization probes, are a powerful tool for the rapid and specific detection of a particular nucleic acid sequence. However, their synthesis costs can be considerable. Since molecular beacon performance is based on its sequence, it is imperative to rationally design an optimal sequence before synthesis. The algorithm presented here uses simple Microsoft Excel formulas and macros to rank candidate sequences. This analysis is carried out using mfold structural predictions along with other free Web-based tools. For smaller laboratories where molecular beacons are not the focus of research, the public domain algorithm described here may be usefully employed to aid in molecular beacon design.

Structure and vibrational spectra of melaminium bis(trifluoroacetate) trihydrate: FT-IR, FT-Raman and quantum chemical calculations.

PubMed

Sangeetha, V; Govindarajan, M; Kanagathara, N; Marchewka, M K; Gunasekaran, S; Anbalagan, G

2014-05-05

Melaminium bis(trifluoroacetate) trihydrate (MTFA), an organic material has been synthesized and single crystals of MTFA have been grown by the slow solvent evaporation method at room temperature. X-ray powder diffraction analysis confirms that MTFA crystal belongs to the monoclinic system with space group P2/c. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on density functional theory (DFT) B3LYP method with 6-311G(d,p) and 6-311++G(d,p) basis sets. The X-ray diffraction data have been compared with the data of optimized molecular structure. The theoretical results show that the crystal structure can be reproduced by optimized geometry and the vibrational frequencies show good agreement with the experimental values. The nuclear magnetic resonance (NMR) chemical shift of the molecule has been calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. HOMO-LUMO, and other related molecular and electronic properties are calculated. The Mulliken and NBO charges have also been calculated and interpreted. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of repeated cycled crystallization on digestibility and molecular structure of glutinous Bora rice starch.

PubMed

Borah, Pallab Kumar; Deka, Sankar Chandra; Duary, Raj Kumar

2017-05-15

The effects of repeated cycled crystallization on the digestibility and molecular structure of glutinous Bora rice starch were investigated. Temperature cycle 4/45°C; cycle duration 5d; time interval of cycles 24h; and starch to water ratio 1:2 were found to be optimum for SDS (slow digestible starch) product development. The SDS content increased from 18.01±2.11% to 82.81±2.34%. An increase in the resistance to digestion, crystallinity, molecular weight, polydispersity and molecular order was observed in the optimal SDS product. Notably, the FT-IR peak at 947cm -1 and XRD peaks at 2θ≈13° and 20° in the optimal SDS product indicated the formation of V-type complexes even without the presence of co-polymers. Birefringence studies showed a loss of typical Maltese cross in the SDS product and revealed a reorientation of crystalline structures within starch granules, suggestive of imperfect crystallite development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimizing physical energy functions for protein folding.

PubMed

Fujitsuka, Yoshimi; Takada, Shoji; Luthey-Schulten, Zaida A; Wolynes, Peter G

2004-01-01

We optimize a physical energy function for proteins with the use of the available structural database and perform three benchmark tests of the performance: (1) recognition of native structures in the background of predefined decoy sets of Levitt, (2) de novo structure prediction using fragment assembly sampling, and (3) molecular dynamics simulations. The energy parameter optimization is based on the energy landscape theory and uses a Monte Carlo search to find a set of parameters that seeks the largest ratio deltaE(s)/DeltaE for all proteins in a training set simultaneously. Here, deltaE(s) is the stability gap between the native and the average in the denatured states and DeltaE is the energy fluctuation among these states. Some of the energy parameters optimized are found to show significant correlation with experimentally observed quantities: (1) In the recognition test, the optimized function assigns the lowest energy to either the native or a near-native structure among many decoy structures for all the proteins studied. (2) Structure prediction with the fragment assembly sampling gives structure models with root mean square deviation less than 6 A in one of the top five cluster centers for five of six proteins studied. (3) Structure prediction using molecular dynamics simulation gives poorer performance, implying the importance of having a more precise description of local structures. The physical energy function solely inferred from a structural database neither utilizes sequence information from the family of the target nor the outcome of the secondary structure prediction but can produce the correct native fold for many small proteins. Copyright 2003 Wiley-Liss, Inc.

jMetalCpp: optimizing molecular docking problems with a C++ metaheuristic framework.

PubMed

López-Camacho, Esteban; García Godoy, María Jesús; Nebro, Antonio J; Aldana-Montes, José F

2014-02-01

Molecular docking is a method for structure-based drug design and structural molecular biology, which attempts to predict the position and orientation of a small molecule (ligand) in relation to a protein (receptor) to produce a stable complex with a minimum binding energy. One of the most widely used software packages for this purpose is AutoDock, which incorporates three metaheuristic techniques. We propose the integration of AutoDock with jMetalCpp, an optimization framework, thereby providing both single- and multi-objective algorithms that can be used to effectively solve docking problems. The resulting combination of AutoDock + jMetalCpp allows users of the former to easily use the metaheuristics provided by the latter. In this way, biologists have at their disposal a richer set of optimization techniques than those already provided in AutoDock. Moreover, designers of metaheuristic techniques can use molecular docking for case studies, which can lead to more efficient algorithms oriented to solving the target problems.  jMetalCpp software adapted to AutoDock is freely available as a C++ source code at http://khaos.uma.es/AutodockjMetal/.

DFT study of the effect of substitution on the molecular structure of copper phthalocyanine

NASA Astrophysics Data System (ADS)

Kaur, Prabhjot; Sachdeva, Ritika; Singh, Sukhwinder; Saini, G. S. S.

2016-05-01

To study the effect of sulfonic acid group as substituent on the molecular structure of an organic compound copper Phthalocyanine, the optimized geometry, mulliken charges, energies and dipole momemts of copper phthalocyanine and copper phthalocyaninetetrasulfonic acid tetra sodium salt have been investigated using density functional theory. Also to predict the change in reactive sites after substitution, molecular electrostatic potential maps for both the molecules have been calculated.

Strategies for the Optimization of Natural Leads to Anticancer Drugs or Drug Candidates

PubMed Central

Xiao, Zhiyan; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

2015-01-01

Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. More often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. Generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve ADMET profiles and chemical accessibility associated with the natural leads. Optimization strategies involve direct chemical manipulation of functional groups, structure-activity relationship-directed optimization and pharmacophore-oriented molecular design based on the natural templates. Both fundamental medicinal chemistry principles (e.g., bio-isosterism) and state-of-the-art computer-aided drug design techniques (e.g., structure-based design) can be applied to facilitate optimization efforts. In this review, the strategies to optimize natural leads to anticancer drugs or drug candidates are illustrated with examples and described according to their purposes. Furthermore, successful case studies on lead optimization of bioactive compounds performed in the Natural Products Research Laboratories at UNC are highlighted. PMID:26359649

A device-oriented optimizer for solving ground state problems on an approximate quantum computer, Part II: Experiments for interacting spin and molecular systems

NASA Astrophysics Data System (ADS)

Kandala, Abhinav; Mezzacapo, Antonio; Temme, Kristan; Bravyi, Sergey; Takita, Maika; Chavez-Garcia, Jose; Córcoles, Antonio; Smolin, John; Chow, Jerry; Gambetta, Jay

Hybrid quantum-classical algorithms can be used to find variational solutions to generic quantum problems. Here, we present an experimental implementation of a device-oriented optimizer that uses superconducting quantum hardware. The experiment relies on feedback between the quantum device and classical optimization software which is robust to measurement noise. Our device-oriented approach uses naturally available interactions for the preparation of trial states. We demonstrate the application of this technique for solving interacting spin and molecular structure problems.

From laptop to benchtop to bedside: Structure-based Drug Design on Protein Targets

PubMed Central

Chen, Lu; Morrow, John K.; Tran, Hoang T.; Phatak, Sharangdhar S.; Du-Cuny, Lei; Zhang, Shuxing

2013-01-01

As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting protein-ligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches. PMID:22316152

DFT approach to (benzylthio)acetic acid: Conformational search, molecular (monomer and dimer) structure, vibrational spectroscopy and some electronic properties

NASA Astrophysics Data System (ADS)

Sienkiewicz-Gromiuk, Justyna

2018-01-01

The DFT studies were carried out with the B3LYP method utilizing the 6-31G and 6-311++G(d,p) basis sets depending on whether the aim of calculations was to gain the geometry at equilibrium, or to calculate the optimized molecular structure of (benzylthio)acetic acid (Hbta) in the forms of monomer and dimer. The minimum conformational energy search was followed by the potential energy surface (PES) scan of all rotary bonds existing in the acid molecule. The optimized geometrical monomeric and dimeric structures of the title compound were compared with the experimental structural data in the solid state. The detailed vibrational interpretation of experimental infrared and Raman bands was performed on the basis of theoretically simulated ESFF-scaled wavenumbers calculated for the monomer and dimer structures of Hbta. The electronic characteristics of Hbta is also presented in terms of Mulliken atomic charges, frontier molecular orbitals and global reactivity descriptors. Additionally, the MEP and ESP surfaces were computed to predict coordination sites for potential metal complex formation.

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

PubMed

Mörschel, Philipp; Schmidt, Martin U

2015-01-01

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

Molecular structure, interatomic interactions and vibrational analysis of 1,4-diazabicyclo[3.2.1]octane parent ring system

NASA Astrophysics Data System (ADS)

Britvin, Sergey N.; Rumyantsev, Andrey M.; Zobnina, Anastasia E.; Padkina, Marina V.

2017-02-01

Molecular structure of 1,4-diazabicyclo[3.2.1]octane, a parent ring of TAN1251 family of alkaloids, is herein characterized for the first time in comparison with the structure of nortropane (8-azabicyclo[3.2.1]octane), the parent framework of tropane ring system. The methods of study involve X-ray structural analysis, DFT geometry optimizations with infrared frequency calculations followed by natural bond orbital (NBO) analysis, and vibrational analysis of infrared spectrum.

Optimized expression and purification of NavAb provide the structural insight into the voltage dependence.

PubMed

Irie, Katsumasa; Haga, Yukari; Shimomura, Takushi; Fujiyoshi, Yoshinori

2018-01-01

Voltage-gated sodium channels are crucial for electro-signalling in living systems. Analysis of the molecular mechanism requires both fine electrophysiological evaluation and high-resolution channel structures. Here, we optimized a dual expression system of NavAb, which is a well-established standard of prokaryotic voltage-gated sodium channels, for E. coli and insect cells using a single plasmid vector to analyse high-resolution protein structures and measure large ionic currents. Using this expression system, we evaluated the voltage dependence and determined the crystal structures of NavAb wild-type and two mutants, E32Q and N49K, whose voltage dependence were positively shifted and essential interactions were lost in voltage sensor domain. The structural and functional comparison elucidated the molecular mechanisms of the voltage dependence of prokaryotic voltage-gated sodium channels. © 2017 Federation of European Biochemical Societies.

Computational strategies for the automated design of RNA nanoscale structures from building blocks using NanoTiler.

PubMed

Bindewald, Eckart; Grunewald, Calvin; Boyle, Brett; O'Connor, Mary; Shapiro, Bruce A

2008-10-01

One approach to designing RNA nanoscale structures is to use known RNA structural motifs such as junctions, kissing loops or bulges and to construct a molecular model by connecting these building blocks with helical struts. We previously developed an algorithm for detecting internal loops, junctions and kissing loops in RNA structures. Here we present algorithms for automating or assisting many of the steps that are involved in creating RNA structures from building blocks: (1) assembling building blocks into nanostructures using either a combinatorial search or constraint satisfaction; (2) optimizing RNA 3D ring structures to improve ring closure; (3) sequence optimisation; (4) creating a unique non-degenerate RNA topology descriptor. This effectively creates a computational pipeline for generating molecular models of RNA nanostructures and more specifically RNA ring structures with optimized sequences from RNA building blocks. We show several examples of how the algorithms can be utilized to generate RNA tecto-shapes.

Computational strategies for the automated design of RNA nanoscale structures from building blocks using NanoTiler☆

PubMed Central

Bindewald, Eckart; Grunewald, Calvin; Boyle, Brett; O’Connor, Mary; Shapiro, Bruce A.

2013-01-01

One approach to designing RNA nanoscale structures is to use known RNA structural motifs such as junctions, kissing loops or bulges and to construct a molecular model by connecting these building blocks with helical struts. We previously developed an algorithm for detecting internal loops, junctions and kissing loops in RNA structures. Here we present algorithms for automating or assisting many of the steps that are involved in creating RNA structures from building blocks: (1) assembling building blocks into nanostructures using either a combinatorial search or constraint satisfaction; (2) optimizing RNA 3D ring structures to improve ring closure; (3) sequence optimisation; (4) creating a unique non-degenerate RNA topology descriptor. This effectively creates a computational pipeline for generating molecular models of RNA nanostructures and more specifically RNA ring structures with optimized sequences from RNA building blocks. We show several examples of how the algorithms can be utilized to generate RNA tecto-shapes. PMID:18838281

Porphyrin-sensitized solar cells: systematic molecular optimization, coadsorption and cosensitization.

PubMed

Song, Heli; Liu, Qingyun; Xie, Yongshu

2018-02-15

As a promising low-cost solar energy conversion technique, dye-sensitized solar cells have undergone spectacular development since 1991. For practical applications, improvement of power conversion efficiency has always been one of the major research topics. Porphyrins are outstanding sensitizers endowed with strong sunlight harvesting ability in the visible region and multiple reaction sites available for functionalization. However, judicious molecular design in consideration of light-harvest, energy levels, operational dynamics, adsorption geometry and suppression of back reactions is specifically required for achieving excellent photovoltaic performance. This feature article highlights some of the recently developed porphyrin sensitizers, especially focusing on the systematic dye structure optimization approach in combination with coadsorption and cosensitization methods in pursuing higher efficiencies. Herein, we expect to provide more insights into the structure-performance correlation and molecular engineering strategies in a stepwise manner.

Introductory Molecular Orbital Theory: An Honors General Chemistry Computational Lab as Implemented Using Three-Dimensional Modeling Software

ERIC Educational Resources Information Center

Ruddick, Kristie R.; Parrill, Abby L.; Petersen, Richard L.

2012-01-01

In this study, a computational molecular orbital theory experiment was implemented in a first-semester honors general chemistry course. Students used the GAMESS (General Atomic and Molecular Electronic Structure System) quantum mechanical software (as implemented in ChemBio3D) to optimize the geometry for various small molecules. Extended Huckel…

Molecular design for enhancement of ocular penetration.

PubMed

Shirasaki, Yoshihisa

2008-07-01

Over the past two decades, many oral drugs have been designed in consideration of physicochemical properties to attain optimal pharmacokinetic properties. This strategy significantly reduced attrition in drug development owing to inadequate pharmacokinetics during the last decade. On the other hand, most ophthalmic drugs are generated from reformulation of other therapeutic dosage forms. Therefore, the modification of formulations has been used mainly as the approach to improve ocular pharmacokinetics. However, to maximize ocular pharmacokinetic properties, a specific molecular design for ocular drug is preferable. Passive diffusion of drugs across the cornea membranes requires appropriate lipophilicity and aqueous solubility. Improvement of such physicochemical properties has been achieved by structure optimization or prodrug approaches. This review discusses the current knowledge about ophthalmic drugs adapted from systemic drugs and molecular design for ocular drugs. I propose the approaches for molecular design to obtain the optimal ocular penetration into anterior segment based on published studies to date.

Automated design evolution of stereochemically randomized protein foldamers

NASA Astrophysics Data System (ADS)

Ranbhor, Ranjit; Kumar, Anil; Patel, Kirti; Ramakrishnan, Vibin; Durani, Susheel

2018-05-01

Diversification of chain stereochemistry opens up the possibilities of an ‘in principle’ increase in the design space of proteins. This huge increase in the sequence and consequent structural variation is aimed at the generation of smart materials. To diversify protein structure stereochemically, we introduced L- and D-α-amino acids as the design alphabet. With a sequence design algorithm, we explored the usage of specific variables such as chirality and the sequence of this alphabet in independent steps. With molecular dynamics, we folded stereochemically diverse homopolypeptides and evaluated their ‘fitness’ for possible design as protein-like foldamers. We propose a fitness function to prune the most optimal fold among 1000 structures simulated with an automated repetitive simulated annealing molecular dynamics (AR-SAMD) approach. The highly scored poly-leucine fold with sequence lengths of 24 and 30 amino acids were later sequence-optimized using a Dead End Elimination cum Monte Carlo based optimization tool. This paper demonstrates a novel approach for the de novo design of protein-like foldamers.

Packaging double-helical DNA into viral capsids.

PubMed

LaMarque, Jaclyn C; Le, Thuc-Vy L; Harvey, Stephen C

2004-02-15

DNA packaging in bacteriophage P4 has been examined using a molecular mechanics model with a reduced representation containing one pseudoatom per turn of the double helix. The model is a discretized version of an elastic continuum model. The DNA is inserted piecewise into the model capsid, with the structure being reoptimized after each piece is inserted. Various optimization protocols were investigated, and it was found that molecular dynamics at a very low temperature (0.3 K) produces the optimal packaged structure. This structure is a concentric spool, rather than the coaxial spool that has been commonly accepted for so many years. This geometry, which was originally suggested by Hall and Schellman in 1982 (Biopolymers Vol. 21, pp. 2011-2031), produces a lower overall elastic energy than coaxial spooling. Copyright 2003 Wiley Periodicals, Inc.

Advanced understanding on electronic structure of molecular semiconductors and their interfaces

NASA Astrophysics Data System (ADS)

Akaike, Kouki

2018-03-01

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

A bio-inspired structural health monitoring system based on ambient vibration

NASA Astrophysics Data System (ADS)

Lin, Tzu-Kang; Kiremidjian, Anne; Lei, Chi-Yang

2010-11-01

A structural health monitoring (SHM) system based on naïve Bayesian (NB) damage classification and DNA-like expression data was developed in this research. Adapted from the deoxyribonucleic acid (DNA) array concept in molecular biology, the proposed structural health monitoring system is constructed utilizing a double-tier regression process to extract the expression array from the structural time history recorded during external excitations. The extracted array is symbolized as the various genes of the structure from the viewpoint of molecular biology and reflects the possible damage conditions prevalent in the structure. A scaled down, six-story steel building mounted on the shaking table of the National Center for Research on Earthquake Engineering (NCREE) was used as the benchmark. The structural response at different damage levels and locations under ambient vibration was collected to support the database for the proposed SHM system. To improve the precision of detection in practical applications, the system was enhanced by an optimization process using the likelihood selection method. The obtained array representing the DNA array of the health condition of the structure was first evaluated and ranked. A total of 12 groups of expression arrays were regenerated from a combination of four damage conditions. To keep the length of the array unchanged, the best 16 coefficients from every expression array were selected to form the optimized SHM system. Test results from the ambient vibrations showed that the detection accuracy of the structural damage could be greatly enhanced by the optimized expression array, when compared to the original system. Practical verification also demonstrated that a rapid and reliable result could be given by the final system within 1 min. The proposed system implements the idea of transplanting the DNA array concept from molecular biology into the field of SHM.

Adaptive frozen orbital treatment for the fragment molecular orbital method combined with density-functional tight-binding

NASA Astrophysics Data System (ADS)

Nishimoto, Yoshio; Fedorov, Dmitri G.

2018-02-01

The exactly analytic gradient is derived and implemented for the fragment molecular orbital (FMO) method combined with density-functional tight-binding (DFTB) using adaptive frozen orbitals. The response contributions which arise from freezing detached molecular orbitals on the border between fragments are computed by solving Z-vector equations. The accuracy of the energy, its gradient, and optimized structures is verified on a set of representative inorganic materials and polypeptides. FMO-DFTB is applied to optimize the structure of a silicon nano-wire, and the results are compared to those of density functional theory and experiment. FMO accelerates the DFTB calculation of a boron nitride nano-ring with 7872 atoms by a factor of 406. Molecular dynamics simulations using FMO-DFTB applied to a 10.7 μm chain of boron nitride nano-rings, consisting of about 1.2 × 106 atoms, reveal the rippling and twisting of nano-rings at room temperature.

Clustering molecular dynamics trajectories for optimizing docking experiments.

PubMed

De Paris, Renata; Quevedo, Christian V; Ruiz, Duncan D; Norberto de Souza, Osmar; Barros, Rodrigo C

2015-01-01

Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

Performances and working mechanism of a novel polycarboxylate superplasticizer synthesized through changing molecular topological structure.

PubMed

Liu, Xiao; Guan, Jianan; Lai, Guanghong; Wang, Ziming; Zhu, Jie; Cui, Suping; Lan, Mingzhang; Li, Huiqun

2017-10-15

A novel star-shaped polycarboxylate superplasticizer (SPCE) was synthesized through a simple two-step method. 1 H Nuclear Magnetic Resonance ( 1 H NMR) and Infrared Spectroscopy (IR) measurements were used for structural characterization. SPCE and comb-shaped polycarboxylate superplasticizer (CPCE) with same molecular weights were designed and synthesized. The cement paste containing SPCE exhibited better fluidity, fluidity retention, water reduction, 25% lower saturated dosage of PCE, 10% longer setting time, lower hydration heat, more delayed hydration heat evolution and lower amount of hydration products at early ages. Furthermore, the adsorption behavior of SPCE and CPCE in cement pastes and the zeta potential were investigated, and then the working mechanism of SPCE was theoretically explained. It is interesting that changing topological structure from comb-shape to star-shape can achieve the optimization of dispersion effect, and further improve the working effectiveness. The aims of this study are to provide a new avenue to synthesize superplasticizer with novel structure achieving the chemical diversity of superplasticizer structure, and to verify the contribution of optimizing molecular shape. This new type of superplasticizer can be used as a rheology modifying agent in fresh cement-based materials. Copyright © 2017 Elsevier Inc. All rights reserved.

ADME evaluation in drug discovery. 1. Applications of genetic algorithms to the prediction of blood-brain partitioning of a large set of drugs.

PubMed

Hou, Tingjun; Xu, Xiaojie

2002-12-01

In this study, the relationships between the brain-blood concentration ratio of 96 structurally diverse compounds with a large number of structurally derived descriptors were investigated. The linear models were based on molecular descriptors that can be calculated for any compound simply from a knowledge of its molecular structure. The linear correlation coefficients of the models were optimized by genetic algorithms (GAs), and the descriptors used in the linear models were automatically selected from 27 structurally derived descriptors. The GA optimizations resulted in a group of linear models with three or four molecular descriptors with good statistical significance. The change of descriptor use as the evolution proceeds demonstrates that the octane/water partition coefficient and the partial negative solvent-accessible surface area multiplied by the negative charge are crucial to brain-blood barrier permeability. Moreover, we found that the predictions using multiple QSPR models from GA optimization gave quite good results in spite of the diversity of structures, which was better than the predictions using the best single model. The predictions for the two external sets with 37 diverse compounds using multiple QSPR models indicate that the best linear models with four descriptors are sufficiently effective for predictive use. Considering the ease of computation of the descriptors, the linear models may be used as general utilities to screen the blood-brain barrier partitioning of drugs in a high-throughput fashion.

Structural characterization/correlation of calorimetric properties of coal fluids: Final report, September 1, 1985--August 31, 1988

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

Starling, K.E.; Mallinson, R.G.; Li, M.H.

The objective of this research is to examine the relationship between the calorimetric properties of coal fluids and their molecular functional group composition. Coal fluid samples which have had their calorimetric properties measured are characterized using proton NMR, IR, and elemental analysis. These characterizations are then used in a chemical structural model to determine the composition of the coal fluid in terms of the important molecular functional groups. These functional groups are particularly important in determining the intramolecular based properties of a fluid, such as ideal gas heat capacities. Correlational frameworks for ideal gas heat capacities are then examined withinmore » an existing equation of state methodology to determine an optimal correlation. The optimal correlation for obtaining the characterization/chemical structure information and the sensitivity of the correlation to the characterization and structural model is examined. 8 refs.« less

Structural characterization/correlation of calorimetric properties of coal fluids: Second annual report, September 1, 1986-August 31, 1987

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

Starling, K.E.; Mallinson, R.G.; Li, M.H.

The objective of this research is to examine the relationship between the calorimetric properties of coal fluids and their molecular functional group composition. Coal fluid samples which have had their calorimetric properties measured are characterized using proton NMR, ir, and elemental analysis. These characterizations are then used in a chemical structural model to determine the composition of the coal fluid in terms of the important molecular functional groups. These functional groups are particularly important in determining the intramolecular based properties of a fluid, such as ideal gas heat capacities. Correlational frameworks for ideal gas heat capacities are then examined withinmore » an existing equation of state methodology to determine an optimal correlation. The optimal correlation for obtaining the characterization/chemical structure information and the sensitivity of the correlation to the characterization and structural model is examined.« less

Structural characterization/correlation of calorimetric properties of coal fluids. First annual report, September 1, 1985-August 31, 1986

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

Starling, K.E.; Mallinson, R.G.; Li, M.H.

The objective of this research is to examine the relationship between the calorimetric properties of coal liquids and their molecular functional group composition. Coal liquid samples which have had their calorimetric properties measured are characterized using proton NMR, ir and elemental analysis. These characterizations are then used in a chemical structural model to determine the composition of the coal liquid in terms of the important molecular functional groups. These functional groups are particularly important in determining the intramolecular based properties of a fluid, such as ideal gas heat capacities. Correlational frameworks for heat capacities will then be examined within anmore » existing equation of state methodology to determine an optimal correlation. Also, the optimal recipe for obtaining the characterization/chemical structure information and the sensitivity of the correlation to the characterization and structural model will be examined and determined. 7 refs.« less

Structural diversity requires individual optimization of ethanol concentration in polysaccharide precipitation.

PubMed

Xu, Jun; Yue, Rui-Qi; Liu, Jing; Ho, Hing-Man; Yi, Tao; Chen, Hu-Biao; Han, Quan-Bin

2014-06-01

Ethanol precipitation is one of the most widely used methods for preparing natural polysaccharides, in which ethanol concentration significantly affects the precipitate yield, however, is usually set at 70-80%. Whether the standardization of ethanol concentration is appropriate has not been investigated. In the present study, the precipitation yields produced in varied ethanol concentrations (10-90%) were qualitatively and quantitatively evaluated by HPGPC (high-performance gel-permeation chromatography), using two series of standard glucans, namely dextrans and pullulans, as reference samples, and then eight natural samples. The results indicated that the response of a polysaccharide's chemical structure, with diversity in structural features and molecular sizes, to ethanol concentration is the decisive factor in precipitation of these glucans. Polysaccharides with different structural features, even though they have similar molecular weights, exhibit significantly different precipitation behaviors. For a specific glucan, the lower its molecular size, the higher the ethanol concentration needed for complete precipitation. The precipitate yield varied from 10% to 100% in 80% ethanol as the molecular size increased from 1kDa to 270kDa. This paper aims to draw scientists' attention to the fact that, in extracting natural polysaccharides by ethanol precipitation, the ethanol concentration must be individually optimized for each type of material. Copyright © 2014 Elsevier B.V. All rights reserved.

QSAR as a random event: modeling of nanoparticles uptake in PaCa2 cancer cells.

PubMed

Toropov, Andrey A; Toropova, Alla P; Puzyn, Tomasz; Benfenati, Emilio; Gini, Giuseppina; Leszczynska, Danuta; Leszczynski, Jerzy

2013-06-01

Quantitative structure-property/activity relationships (QSPRs/QSARs) are a tool to predict various endpoints for various substances. The "classic" QSPR/QSAR analysis is based on the representation of the molecular structure by the molecular graph. However, simplified molecular input-line entry system (SMILES) gradually becomes most popular representation of the molecular structure in the databases available on the Internet. Under such circumstances, the development of molecular descriptors calculated directly from SMILES becomes attractive alternative to "classic" descriptors. The CORAL software (http://www.insilico.eu/coral) is provider of SMILES-based optimal molecular descriptors which are aimed to correlate with various endpoints. We analyzed data set on nanoparticles uptake in PaCa2 pancreatic cancer cells. The data set includes 109 nanoparticles with the same core but different surface modifiers (small organic molecules). The concept of a QSAR as a random event is suggested in opposition to "classic" QSARs which are based on the only one distribution of available data into the training and the validation sets. In other words, five random splits into the "visible" training set and the "invisible" validation set were examined. The SMILES-based optimal descriptors (obtained by the Monte Carlo technique) for these splits are calculated with the CORAL software. The statistical quality of all these models is good. Copyright © 2013 Elsevier Ltd. All rights reserved.

In silico modelling and molecular dynamics simulation studies of thiazolidine based PTP1B inhibitors.

PubMed

Mahapatra, Manoj Kumar; Bera, Krishnendu; Singh, Durg Vijay; Kumar, Rajnish; Kumar, Manoj

2018-04-01

Protein tyrosine phosphatase 1B (PTP1B) has been identified as a negative regulator of insulin and leptin signalling pathway; hence, it can be considered as a new therapeutic target of intervention for the treatment of type 2 diabetes. Inhibition of this molecular target takes care of both diabetes and obesity, i.e. diabestiy. In order to get more information on identification and optimization of lead, pharmacophore modelling, atom-based 3D QSAR, docking and molecular dynamics studies were carried out on a set of ligands containing thiazolidine scaffold. A six-point pharmacophore model consisting of three hydrogen bond acceptor (A), one negative ionic (N) and two aromatic rings (R) with discrete geometries as pharmacophoric features were developed for a predictive 3D QSAR model. The probable binding conformation of the ligands within the active site was studied through molecular docking. The molecular interactions and the structural features responsible for PTP1B inhibition and selectivity were further supplemented by molecular dynamics simulation study for a time scale of 30 ns. The present investigation has identified some of the indispensible structural features of thiazolidine analogues which can further be explored to optimize PTP1B inhibitors.

Molecular docking.

PubMed

Morris, Garrett M; Lim-Wilby, Marguerita

2008-01-01

Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

A Short Review of the Generation of Molecular Descriptors and Their Applications in Quantitative Structure Property/Activity Relationships.

PubMed

Sahoo, Sagarika; Adhikari, Chandana; Kuanar, Minati; Mishra, Bijay K

2016-01-01

Synthesis of organic compounds with specific biological activity or physicochemical characteristics needs a thorough analysis of the enumerable data set obtained from literature. Quantitative structure property/activity relationships have made it simple by predicting the structure of the compound with any optimized activity. For that there is a paramount data set of molecular descriptors (MD). This review is a survey on the generation of the molecular descriptors and its probable applications in QSP/AR. Literatures have been collected from a wide class of research journals, citable web reports, seminar proceedings and books. The MDs were classified according to their generation. The applications of the MDs on the QSP/AR have also been reported in this review. The MDs can be classified into experimental and theoretical types, having a sub classification of the later into structural and quantum chemical descriptors. The structural parameters are derived from molecular graphs or topology of the molecules. Even the pixel of the molecular image can be used as molecular descriptor. In QSPR studies the physicochemical properties include boiling point, heat capacity, density, refractive index, molar volume, surface tension, heat of formation, octanol-water partition coefficient, solubility, chromatographic retention indices etc. Among biological activities toxicity, antimalarial activity, sensory irritant, potencies of local anesthetic, tadpole narcosis, antifungal activity, enzyme inhibiting activity are some important parameters in the QSAR studies. The classification of the MDs is mostly generic in nature. The application of the MDs in QSP/AR also has a generic link. Experimental MDs are more suitable in correlation analysis than the theoretical ones but are more expensive for generation. In advent of sophisticated computational tools and experimental design proliferation of MDs is inevitable, but for a highly optimized MD, studies on generation of MD is an unending process.

3D-quantitative structure-activity relationship studies on benzothiadiazepine hydroxamates as inhibitors of tumor necrosis factor-alpha converting enzyme.

PubMed

Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2008-04-01

A set of 29 benzothiadiazepine hydroxamates having selective tumor necrosis factor-alpha converting enzyme inhibitory activity were used to compare the quality and predictive power of 3D-quantitative structure-activity relationship, comparative molecular field analysis, and comparative molecular similarity indices models for the atom-based, centroid/atom-based, data-based, and docked conformer-based alignment. Removal of two outliers from the initial training set of molecules improved the predictivity of models. Among the 3D-quantitative structure-activity relationship models developed using the above four alignments, the database alignment provided the optimal predictive comparative molecular field analysis model for the training set with cross-validated r(2) (q(2)) = 0.510, non-cross-validated r(2) = 0.972, standard error of estimates (s) = 0.098, and F = 215.44 and the optimal comparative molecular similarity indices model with cross-validated r(2) (q(2)) = 0.556, non-cross-validated r(2) = 0.946, standard error of estimates (s) = 0.163, and F = 99.785. These models also showed the best test set prediction for six compounds with predictive r(2) values of 0.460 and 0.535, respectively. The contour maps obtained from 3D-quantitative structure-activity relationship studies were appraised for activity trends for the molecules analyzed. The comparative molecular similarity indices models exhibited good external predictivity as compared with that of comparative molecular field analysis models. The data generated from the present study helped us to further design and report some novel and potent tumor necrosis factor-alpha converting enzyme inhibitors.

Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity.

PubMed

Sarvagalla, Sailu; Singh, Vivek Kumar; Ke, Yi-Yu; Shiao, Hui-Yi; Lin, Wen-Hsing; Hsieh, Hsing-Pang; Hsu, John T A; Coumar, Mohane Selvaraj

2015-01-01

Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as molecular weight (MW) and lipophilicity occurs. This could be effectively tackled by the right choice of hit compounds for optimization. In this regard, ligand efficiency (LE) and ligand efficiency dependent lipophilicity (LELP) indices are more often used to choose fragment-like hits for optimization. To identify hits with appropriate LE, we used a MW cut-off <250, and pyrazole structure to filter HTS library. Next, structure-based virtual screening using software (Libdock and Glide) in the Aurora A crystal structure (PDB ID: 3E5A) was carried out, and the top scoring 18 compounds tested for Aurora A enzyme inhibition. This resulted in the identification of a novel tetrahydro-pyrazolo-isoquinoline hit 7 (IC50 = 852 nM, LE = 0.44, LELP = 8.36) with fragment-like properties suitable for further hit optimization. Moreover, hit 7 was found to be selective for Aurora A (Aurora B IC50 = 35,150 nM) and the possible reasons for selectivity investigated by docking two tautomeric forms (2H- and 3H-pyrazole) of 7 in Auroras A and B (PDB ID: 4AF3) crystal structures. This docking study shows that the major 3H-pyrazole tautomer of 7 binds in Aurora A stronger than in Aurora B.

Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2 H- and 3 H-pyrazolo tautomers for Aurora kinase A selectivity

NASA Astrophysics Data System (ADS)

Sarvagalla, Sailu; Singh, Vivek Kumar; Ke, Yi-Yu; Shiao, Hui-Yi; Lin, Wen-Hsing; Hsieh, Hsing-Pang; Hsu, John T. A.; Coumar, Mohane Selvaraj

2015-01-01

Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as molecular weight (MW) and lipophilicity occurs. This could be effectively tackled by the right choice of hit compounds for optimization. In this regard, ligand efficiency (LE) and ligand efficiency dependent lipophilicity (LELP) indices are more often used to choose fragment-like hits for optimization. To identify hits with appropriate LE, we used a MW cut-off <250, and pyrazole structure to filter HTS library. Next, structure-based virtual screening using software (Libdock and Glide) in the Aurora A crystal structure (PDB ID: 3E5A) was carried out, and the top scoring 18 compounds tested for Aurora A enzyme inhibition. This resulted in the identification of a novel tetrahydro-pyrazolo-isoquinoline hit 7 (IC50 = 852 nM, LE = 0.44, LELP = 8.36) with fragment-like properties suitable for further hit optimization. Moreover, hit 7 was found to be selective for Aurora A (Aurora B IC50 = 35,150 nM) and the possible reasons for selectivity investigated by docking two tautomeric forms (2 H- and 3 H-pyrazole) of 7 in Auroras A and B (PDB ID: 4AF3) crystal structures. This docking study shows that the major 3 H-pyrazole tautomer of 7 binds in Aurora A stronger than in Aurora B.

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

DTIC Science & Technology

2009-11-01

dynamics of the complex predicted by multiple molecular dynamics simulations , and discuss further structural optimization to achieve better in vivo efficacy...complex with BoNTAe and the dynamics of the complex predicted by multiple molecular dynamics simulations (MMDSs). On the basis of the 3D model, we discuss...is unlimited whereas AHP exhibited 54% inhibition under the same conditions (Table 1). Computer Simulation Twenty different molecular dynamics

Structure and Activity of a New Low Molecular Weight Heparin Produced by Enzymatic Ultrafiltration

PubMed Central

FU, LI; ZHANG, FUMING; LI, GUOYUN; ONISHI, AKIHIRO; BHASKAR, UJJWAL; SUN, PEILONG; LINHARDT, ROBERT J.

2014-01-01

The standard process for preparing the low molecular weight heparin (LMWH) tinzaparin, through the partial enzymatic depolymerization of heparin, results in a reduced yield due to the formation of a high content of undesired disaccharides and tetrasaccharides. An enzymatic ultrafiltration reactor for LMWH preparation was developed to overcome this problem. The behavior, of the heparin oligosaccharides and polysaccharides using various membranes and conditions, was investigated to optimize this reactor. A novel product, LMWH-II, was produced from the controlled depolymerization of heparin using heparin lyase II in this optimized ultrafiltration reactor. Enzymatic ultrafiltration provides easy control and high yields (>80%) of LMWH-II. The molecular weight properties of LMWH-II were similar to other commercial LMWHs. The structure of LMWH-II closely matched heparin’s core structural features. Most of the common process artifacts, present in many commercial LWMHs, were eliminated as demonstrated by 1D and 2D nuclear magnetic resonance spectroscopy. The antithrombin III and platelet factor-4 binding affinity of LMWH-II were comparable to commercial LMWHs, as was its in vitro anticoagulant activity. PMID:24634007

RNA unrestrained molecular dynamics ensemble improves agreement with experimental NMR data compared to single static structure: a test case

NASA Astrophysics Data System (ADS)

Beckman, Robert A.; Moreland, David; Louise-May, Shirley; Humblet, Christine

2006-05-01

Nuclear magnetic resonance (NMR) provides structural and dynamic information reflecting an average, often non-linear, of multiple solution-state conformations. Therefore, a single optimized structure derived from NMR refinement may be misleading if the NMR data actually result from averaging of distinct conformers. It is hypothesized that a conformational ensemble generated by a valid molecular dynamics (MD) simulation should be able to improve agreement with the NMR data set compared with the single optimized starting structure. Using a model system consisting of two sequence-related self-complementary ribonucleotide octamers for which NMR data was available, 0.3 ns particle mesh Ewald MD simulations were performed in the AMBER force field in the presence of explicit water and counterions. Agreement of the averaged properties of the molecular dynamics ensembles with NMR data such as homonuclear proton nuclear Overhauser effect (NOE)-based distance constraints, homonuclear proton and heteronuclear 1H-31P coupling constant ( J) data, and qualitative NMR information on hydrogen bond occupancy, was systematically assessed. Despite the short length of the simulation, the ensemble generated from it agreed with the NMR experimental constraints more completely than the single optimized NMR structure. This suggests that short unrestrained MD simulations may be of utility in interpreting NMR results. As expected, a 0.5 ns simulation utilizing a distance dependent dielectric did not improve agreement with the NMR data, consistent with its inferior exploration of conformational space as assessed by 2-D RMSD plots. Thus, ability to rapidly improve agreement with NMR constraints may be a sensitive diagnostic of the MD methods themselves.

Optimization of the defects and the nonradiative lifetime of GaAs/AlGaAs double heterostructures

NASA Astrophysics Data System (ADS)

Cevher, Z.; Folkes, P. A.; Hier, H. S.; VanMil, B. L.; Connelly, B. C.; Beck, W. A.; Ren, Y. H.

2018-04-01

We used Raman scattering and time-resolved photoluminescence spectroscopy to investigate the molecular-beam-epitaxy (MBE) growth parameters that optimize the structural defects and therefore the internal radiative quantum efficiency of MBE-grown GaAs/AlGaAs double heterostructures (DH). The DH structures were grown at two different temperatures and three different As/Ga flux ratios to determine the conditions for an optimized structure with the longest nonradiative minority carrier lifetime. Raman scattering measurements show an improvement in the lattice disorder in the AlGaAs and GaAs layers as the As/Ga flux ratio is reduced from 40 to 15 and as the growth temperature is increased from 550 to 595 °C. The optimized structure is obtained with the As/Ga flux ratio equal to 15 and the substrate temperature 595 °C. This is consistent with the fact that the optimized structure has the longest minority carrier lifetime. Moreover, our Raman studies reveal that incorporation of a distributed Bragg reflector layer between the substrate and DH structures significantly reduces the defect density in the subsequent epitaxial layers.

Artificial Bee Colony Optimization of Capping Potentials for Hybrid Quantum Mechanical/Molecular Mechanical Calculations.

PubMed

Schiffmann, Christoph; Sebastiani, Daniel

2011-05-10

We present an algorithmic extension of a numerical optimization scheme for analytic capping potentials for use in mixed quantum-classical (quantum mechanical/molecular mechanical, QM/MM) ab initio calculations. Our goal is to minimize bond-cleavage-induced perturbations in the electronic structure, measured by means of a suitable penalty functional. The optimization algorithm-a variant of the artificial bee colony (ABC) algorithm, which relies on swarm intelligence-couples deterministic (downhill gradient) and stochastic elements to avoid local minimum trapping. The ABC algorithm outperforms the conventional downhill gradient approach, if the penalty hypersurface exhibits wiggles that prevent a straight minimization pathway. We characterize the optimized capping potentials by computing NMR chemical shifts. This approach will increase the accuracy of QM/MM calculations of complex biomolecules.

Clustering Molecular Dynamics Trajectories for Optimizing Docking Experiments

PubMed Central

De Paris, Renata; Quevedo, Christian V.; Ruiz, Duncan D.; Norberto de Souza, Osmar; Barros, Rodrigo C.

2015-01-01

Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand. PMID:25873944

A DAG Scheduling Scheme on Heterogeneous Computing Systems Using Tuple-Based Chemical Reaction Optimization

PubMed Central

Jiang, Yuyi; Shao, Zhiqing; Guo, Yi

2014-01-01

A complex computing problem can be solved efficiently on a system with multiple computing nodes by dividing its implementation code into several parallel processing modules or tasks that can be formulated as directed acyclic graph (DAG) problems. The DAG jobs may be mapped to and scheduled on the computing nodes to minimize the total execution time. Searching an optimal DAG scheduling solution is considered to be NP-complete. This paper proposed a tuple molecular structure-based chemical reaction optimization (TMSCRO) method for DAG scheduling on heterogeneous computing systems, based on a very recently proposed metaheuristic method, chemical reaction optimization (CRO). Comparing with other CRO-based algorithms for DAG scheduling, the design of tuple reaction molecular structure and four elementary reaction operators of TMSCRO is more reasonable. TMSCRO also applies the concept of constrained critical paths (CCPs), constrained-critical-path directed acyclic graph (CCPDAG) and super molecule for accelerating convergence. In this paper, we have also conducted simulation experiments to verify the effectiveness and efficiency of TMSCRO upon a large set of randomly generated graphs and the graphs for real world problems. PMID:25143977

A DAG scheduling scheme on heterogeneous computing systems using tuple-based chemical reaction optimization.

PubMed

Jiang, Yuyi; Shao, Zhiqing; Guo, Yi

2014-01-01

A complex computing problem can be solved efficiently on a system with multiple computing nodes by dividing its implementation code into several parallel processing modules or tasks that can be formulated as directed acyclic graph (DAG) problems. The DAG jobs may be mapped to and scheduled on the computing nodes to minimize the total execution time. Searching an optimal DAG scheduling solution is considered to be NP-complete. This paper proposed a tuple molecular structure-based chemical reaction optimization (TMSCRO) method for DAG scheduling on heterogeneous computing systems, based on a very recently proposed metaheuristic method, chemical reaction optimization (CRO). Comparing with other CRO-based algorithms for DAG scheduling, the design of tuple reaction molecular structure and four elementary reaction operators of TMSCRO is more reasonable. TMSCRO also applies the concept of constrained critical paths (CCPs), constrained-critical-path directed acyclic graph (CCPDAG) and super molecule for accelerating convergence. In this paper, we have also conducted simulation experiments to verify the effectiveness and efficiency of TMSCRO upon a large set of randomly generated graphs and the graphs for real world problems.

Equilibrium Structures and Absorption Spectra for SixOy Molecular Clusters using Density Functional Theory

DTIC Science & Technology

2017-05-05

dependent density functional theory (TD-DFT). The size of the clusters considered is relatively large compared to those considered in previous studies...are characterized by many different geometries, which potentially can be optimized with respect to specific materials design criteria, i.e., molecular...SixOy molecular clusters using density functional theory (DFT). The size of the clusters considered, however, is relatively large compared to those

Basis set construction for molecular electronic structure theory: natural orbital and Gauss-Slater basis for smooth pseudopotentials.

PubMed

Petruzielo, F R; Toulouse, Julien; Umrigar, C J

2011-02-14

A simple yet general method for constructing basis sets for molecular electronic structure calculations is presented. These basis sets consist of atomic natural orbitals from a multiconfigurational self-consistent field calculation supplemented with primitive functions, chosen such that the asymptotics are appropriate for the potential of the system. Primitives are optimized for the homonuclear diatomic molecule to produce a balanced basis set. Two general features that facilitate this basis construction are demonstrated. First, weak coupling exists between the optimal exponents of primitives with different angular momenta. Second, the optimal primitive exponents for a chosen system depend weakly on the particular level of theory employed for optimization. The explicit case considered here is a basis set appropriate for the Burkatzki-Filippi-Dolg pseudopotentials. Since these pseudopotentials are finite at nuclei and have a Coulomb tail, the recently proposed Gauss-Slater functions are the appropriate primitives. Double- and triple-zeta bases are developed for elements hydrogen through argon. These new bases offer significant gains over the corresponding Burkatzki-Filippi-Dolg bases at various levels of theory. Using a Gaussian expansion of the basis functions, these bases can be employed in any electronic structure method. Quantum Monte Carlo provides an added benefit: expansions are unnecessary since the integrals are evaluated numerically.

The impact of structural biology in medicine illustrated with four case studies.

PubMed

Hu, Tiancen; Sprague, Elizabeth R; Fodor, Michelle; Stams, Travis; Clark, Kirk L; Cowan-Jacob, Sandra W

2018-01-01

The contributions of structural biology to drug discovery have expanded over the last 20 years from structure-based ligand optimization to a broad range of clinically relevant topics including the understanding of disease, target discovery, screening for new types of ligands, discovery of new modes of action, addressing clinical challenges such as side effects or resistance, and providing data to support drug registration. This expansion of scope is due to breakthroughs in the technology, which allow structural information to be obtained rapidly and for more complex molecular systems, but also due to the combination of different technologies such as X-ray, NMR, and other biophysical methods, which allows one to get a more complete molecular understanding of disease and ways to treat it. In this review, we provide examples of the types of impact molecular structure information can have in the clinic for both low molecular weight and biologic drug discovery and describe several case studies from our own work to illustrate some of these contributions.

Optimized unconventional superconductivity in a molecular Jahn-Teller metal

PubMed Central

Zadik, Ruth H.; Takabayashi, Yasuhiro; Klupp, Gyöngyi; Colman, Ross H.; Ganin, Alexey Y.; Potočnik, Anton; Jeglič, Peter; Arčon, Denis; Matus, Péter; Kamarás, Katalin; Kasahara, Yuichi; Iwasa, Yoshihiro; Fitch, Andrew N.; Ohishi, Yasuo; Garbarino, Gaston; Kato, Kenichi; Rosseinsky, Matthew J.; Prassides, Kosmas

2015-01-01

Understanding the relationship between the superconducting, the neighboring insulating, and the normal metallic state above Tc is a major challenge for all unconventional superconductors. The molecular A3C60 fulleride superconductors have a parent antiferromagnetic insulator in common with the atom-based cuprates, but here, the C603– electronic structure controls the geometry and spin state of the structural building unit via the on-molecule Jahn-Teller effect. We identify the Jahn-Teller metal as a fluctuating microscopically heterogeneous coexistence of both localized Jahn-Teller–active and itinerant electrons that connects the insulating and superconducting states of fullerides. The balance between these molecular and extended lattice features of the electrons at the Fermi level gives a dome-shaped variation of Tc with interfulleride separation, demonstrating molecular electronic structure control of superconductivity. PMID:26601168

PREFMD: a web server for protein structure refinement via molecular dynamics simulations.

PubMed

Heo, Lim; Feig, Michael

2018-03-15

Refinement of protein structure models is a long-standing problem in structural bioinformatics. Molecular dynamics-based methods have emerged as an avenue to achieve consistent refinement. The PREFMD web server implements an optimized protocol based on the method successfully tested in CASP11. Validation with recent CASP refinement targets shows consistent and more significant improvement in global structure accuracy over other state-of-the-art servers. PREFMD is freely available as a web server at http://feiglab.org/prefmd. Scripts for running PREFMD as a stand-alone package are available at https://github.com/feiglab/prefmd.git. feig@msu.edu. Supplementary data are available at Bioinformatics online.

Enhanced color purity of blue OLEDs based on well-design structure

NASA Astrophysics Data System (ADS)

Du, Qianqian; Wang, Wenjun; Li, Shuhong; Wang, Qingru; Xia, Shuzhen; Zhang, Bingyuan; Wang, Minghong; Fan, Quli

2016-09-01

We have fabricated blue organic light-emitting devices (OLEDs) with higher color purity and stability by optimizing the structure of the Glass/ITO/NPB(50 nm)/ BCzVBi (30 nm)/ TPBi (x nm)/Alq3(20 nm)/LiF/Al. The results show that the introducing of hole blocking layer(HBL) TPBi greatly can improve not only the color purity but the color stability, which owe to its higher the Highest Occupied Molecular Orbital (HOMO) energy levels of 6.2 eV. We expect our work will be useful to optimizing the blue OLEDs structure to enhancing the color property.

Graph Kernels for Molecular Similarity.

PubMed

Rupp, Matthias; Schneider, Gisbert

2010-04-12

Molecular similarity measures are important for many cheminformatics applications like ligand-based virtual screening and quantitative structure-property relationships. Graph kernels are formal similarity measures defined directly on graphs, such as the (annotated) molecular structure graph. Graph kernels are positive semi-definite functions, i.e., they correspond to inner products. This property makes them suitable for use with kernel-based machine learning algorithms such as support vector machines and Gaussian processes. We review the major types of kernels between graphs (based on random walks, subgraphs, and optimal assignments, respectively), and discuss their advantages, limitations, and successful applications in cheminformatics. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis, spectroscopic characterization and crystallographic behavior of a biologically relevant novel indole-fused heterocyclic compound - Experimental and theoretical (DFT) studies

NASA Astrophysics Data System (ADS)

Sharma, Sakshi; Brahmachari, Goutam; Banerjee, Bubun; Nurjamal, Khondekar; Kumar, Abhishek; Srivastava, Ambrish Kumar; Misra, Neeraj; Pandey, Sarvesh Kumar; Rajnikant; Gupta, Vivek K.

2016-08-01

The present communication deals with the eco-friendly synthesis, spectral properties and X-ray crystal structure of an indole derivative - Ethyl 2'-amino-3'-cyano-6'-methyl-5-nitro-2-oxospiro [indoline-3,4'-pyran]-5'-carboxylate. The title compound was synthesized in 87% yield. The crystal structure of the molecule is stabilized by intermolecular Nsbnd H … N, Nsbnd H … O and Csbnd H … π interactions. The molecule is organized in the crystal lattice forming sheet like structure. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 09 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-31 + G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) with frontier orbital gap were presented. The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and density of states (DOS). From the optimized geometry of the molecule, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMOs) of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compound.

Molecular Modeling of the Binding Structures in the Interlayer Adsorption of a Tetracycline Antibiotic by Smectite Clays

NASA Astrophysics Data System (ADS)

Aristilde, L.

2009-12-01

A controlling factor in the fate of antibiotics in the environment is their sequestration in soil particles including clay minerals. Of special interest is the interlayer adsorption by smectite clays, which has been shown to influence both the bioavailability and persistence of antibiotics in the soil environment. However, the interlayer structures of the bound antibiotics, essential to an accurate understanding of the adsorption mechanisms, are not well understood. Molecular simulations of oxytetracycline (OTC) with a model montmorillonite (MONT) clay were performed to gain insights into these structures for tetracycline antibiotics. Monte Carlo simulations were used for explorations of the clay layer spacing required for the adsorption of the antibiotic under different hydration states of the clay interlayer; these preliminary results were validated with previous X-ray diffraction patterns obtained following sorption experiments of OTC with MONT. Molecular dynamics relaxation simulations were performed subsequently in order to obtain geometry-optimized structures of the binding conformations of the intercalated antibiotic in the model MONT layers. This study contributes to a mechanistic understanding of the factors controlling the interlayer adsorption of the tetracycline antibiotics by the expandable smectite clay minerals. Figure 1. Optimized Monte Carlo simulation cell of OTC in the interlayer of MONT: perspective side view (top) and bottom view (bottom).

The study on molecular structure and microbiological activity of alkali metal 3-hydroxyphenylycetates

NASA Astrophysics Data System (ADS)

Samsonowicz, M.; Regulska, E.; Kowczyk-Sadowy, M.; Butarewicz, A.; Lewandowski, W.

2017-10-01

The biological activity of chemical compounds depends on their molecular structure. In this paper molecular structure of 3-hydroxyphenylacetates in comparison to 3-hydroxyphenylacetic acid was studied. FT-IR, FT-Raman and NMR spectroscopy and density functional theory (DFT) calculations was used. The B3LYP/6-311++G(d,p) hybrid functional method was used to calculate optimized geometrical structures of studied compounds. The Mulliken, APT, MK, ChelpG and NBO atomic charges as well as dipole moment and energy values were calculated. Theoretical chemical shifts in NMR spectra and the wavenumbers and intensities of the bands in vibrational spectra were analyzed. Calculated parameters were compared to experimental characteristic of studied compounds. Microbiological analysis of studied compounds was performed relative to: Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and Klebsiella oxytoca. The relationship between spectroscopic and structure parameters of studied compounds in regard to their activity was analyzed.

Structure and activity of a new low-molecular-weight heparin produced by enzymatic ultrafiltration.

PubMed

Fu, Li; Zhang, Fuming; Li, Guoyun; Onishi, Akihiro; Bhaskar, Ujjwal; Sun, Peilong; Linhardt, Robert J

2014-05-01

The standard process for preparing the low-molecular-weight heparin (LMWH) tinzaparin, through the partial enzymatic depolymerization of heparin, results in a reduced yield because of the formation of a high content of undesired disaccharides and tetrasaccharides. An enzymatic ultrafiltration reactor for LMWH preparation was developed to overcome this problem. The behavior, of the heparin oligosaccharides and polysaccharides using various membranes and conditions, was investigated to optimize this reactor. A novel product, LMWH-II, was produced from the controlled depolymerization of heparin using heparin lyase II in this optimized ultrafiltration reactor. Enzymatic ultrafiltration provides easy control and high yields (>80%) of LMWH-II. The molecular weight properties of LMWH-II were similar to other commercial LMWHs. The structure of LMWH-II closely matched heparin's core structural features. Most of the common process artifacts, present in many commercial LWMHs, were eliminated as demonstrated by 1D and 2D nuclear magnetic resonance spectroscopy. The antithrombin III and platelet factor-4 binding affinity of LMWH-II were comparable to commercial LMWHs, as was its in vitro anticoagulant activity. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

The molecular, electronic structures and vibrational spectra of metal-free, N,N'-dideuterio and magnesium tetra-2,3-pyridino-porphyrazines: Density functional calculations.

PubMed

Liu, Zhongqiang; Zhang, Xianxi; Zhang, Yuexing; Li, Renjie; Jiang, Jianzhuang

2006-10-01

A theoretical investigation of the fully optimized geometries and electronic structures of the metal-free (TPdPzH(2)), N,N'-dideuterio (TPdPzD(2)), and magnesium (TPdPzMg) tetra-2,3-pyridino-porphyrazine has been conducted based on density functional theory. The optimized geometries at density functional theory level for these compounds are reported here for the first time. A comparison between the different molecules for the geometry, molecular orbital, and atomic charge is made. The substituent effect of the N atoms on the molecular structures of these compounds is discussed. The IR and Raman spectra for these three compounds have also been calculated at density functional B3LYP level using the 6-31G(d) basis set. Detailed assignments of the NH, NM, and pyridine ring vibrational bands in the IR and Raman spectra have been made based on assistance of animated pictures. The simulated IR spectra of TPdPzH(2) are compared with the experimental absorption spectra, and very good consistency has been found. The isotope effect on the IR and Raman spectra is also discussed.

Chemical graphs, molecular matrices and topological indices in chemoinformatics and quantitative structure-activity relationships.

PubMed

Ivanciuc, Ovidiu

2013-06-01

Chemical and molecular graphs have fundamental applications in chemoinformatics, quantitative structureproperty relationships (QSPR), quantitative structure-activity relationships (QSAR), virtual screening of chemical libraries, and computational drug design. Chemoinformatics applications of graphs include chemical structure representation and coding, database search and retrieval, and physicochemical property prediction. QSPR, QSAR and virtual screening are based on the structure-property principle, which states that the physicochemical and biological properties of chemical compounds can be predicted from their chemical structure. Such structure-property correlations are usually developed from topological indices and fingerprints computed from the molecular graph and from molecular descriptors computed from the three-dimensional chemical structure. We present here a selection of the most important graph descriptors and topological indices, including molecular matrices, graph spectra, spectral moments, graph polynomials, and vertex topological indices. These graph descriptors are used to define several topological indices based on molecular connectivity, graph distance, reciprocal distance, distance-degree, distance-valency, spectra, polynomials, and information theory concepts. The molecular descriptors and topological indices can be developed with a more general approach, based on molecular graph operators, which define a family of graph indices related by a common formula. Graph descriptors and topological indices for molecules containing heteroatoms and multiple bonds are computed with weighting schemes based on atomic properties, such as the atomic number, covalent radius, or electronegativity. The correlation in QSPR and QSAR models can be improved by optimizing some parameters in the formula of topological indices, as demonstrated for structural descriptors based on atomic connectivity and graph distance.

Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans.

PubMed

Golubović, Jelena; Protić, Ana; Otašević, Biljana; Zečević, Mira

2016-04-01

QSRR are mathematically derived relationships between the chromatographic parameters determined for a representative series of analytes in given separation systems and the molecular descriptors accounting for the structural differences among the investigated analytes. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. The aim of the present work was to optimize separation of six angiotensin receptor antagonists, so-called sartans: losartan, valsartan, irbesartan, telmisartan, candesartan cilexetil and eprosartan in a gradient-elution HPLC method. For this purpose, ANN as a mathematical tool was used for establishing a QSRR model based on molecular descriptors of sartans and varied instrumental conditions. The optimized model can be further used for prediction of an external congener of sartans and analysis of the influence of the analyte structure, represented through molecular descriptors, on retention behaviour. Molecular descriptors included in modelling were electrostatic, geometrical and quantum-chemical descriptors: connolly solvent excluded volume non-1,4 van der Waals energy, octanol/water distribution coefficient, polarizability, number of proton-donor sites and number of proton-acceptor sites. Varied instrumental conditions were gradient time, buffer pH and buffer molarity. High prediction ability of the optimized network enabled complete separation of the analytes within the run time of 15.5 min under following conditions: gradient time of 12.5 min, buffer pH of 3.95 and buffer molarity of 25 mM. Applied methodology showed the potential to predict retention behaviour of an external analyte with the properties within the training space. Connolly solvent excluded volume, polarizability and number of proton-acceptor sites appeared to be most influential paramateres on retention behaviour of the sartans. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular Treatment of Nano-Kaolinite Generations.

PubMed

Táborosi, Attila; Szilagyi, Robert K; Zsirka, Balázs; Fónagy, Orsolya; Horváth, Erzsébet; Kristóf, János

2018-06-18

A procedure is developed for defining a compositionally and structurally realistic, atomic-scale description of exfoliated clay nanoparticles from the kaolinite family of phylloaluminosilicates. By use of coordination chemical principles, chemical environments within a nanoparticle can be separated into inner, outer, and peripheral spheres. The edges of the molecular models of nanoparticles were protonated in a validated manner to achieve charge neutrality. Structural optimizations using semiempirical methods (NDDO Hamiltonians and DFTB formalism) and ab initio density functionals with a saturated basis set revealed previously overlooked molecular origins of morphological changes as a result of exfoliation. While the use of semiempirical methods is desirable for the treatment of nanoparticles composed of tens of thousands of atoms, the structural accuracy is rather modest in comparison to DFT methods. We report a comparative survey of our infrared data for untreated crystalline and various exfoliated states of kaolinite and halloysite. Given the limited availability of experimental techniques for providing direct structural information about nano-kaolinite, the vibrational spectra can be considered as an essential tool for validating structural models. The comparison of experimental and calculated stretching and bending frequencies further justified the use of the preferred level of theory. Overall, an optimal molecular model of the defect-free, ideal nano-kaolinite can be composed with respect to stationary structure and curvature of the potential energy surface using the PW91/SVP level of theory with empirical dispersion correction (PW91+D) and polarizable continuum solvation model (PCM) without the need for a scaled quantum chemical force field. This validated theoretical approach is essential in order to follow the formation of exfoliated clays and their surface reactivity that is experimentally unattainable.

Efficient Transition State Optimization of Periodic Structures through Automated Relaxed Potential Energy Surface Scans.

PubMed

Plessow, Philipp N

2018-02-13

This work explores how constrained linear combinations of bond lengths can be used to optimize transition states in periodic structures. Scanning of constrained coordinates is a standard approach for molecular codes with localized basis functions, where a full set of internal coordinates is used for optimization. Common plane wave-codes for periodic boundary conditions almost exlusively rely on Cartesian coordinates. An implementation of constrained linear combinations of bond lengths with Cartesian coordinates is described. Along with an optimization of the value of the constrained coordinate toward the transition states, this allows transition optimization within a single calculation. The approach is suitable for transition states that can be well described in terms of broken and formed bonds. In particular, the implementation is shown to be effective and efficient in the optimization of transition states in zeolite-catalyzed reactions, which have high relevance in industrial processes.

Vibrational, DFT, and thermal analysis of 2,4,6-triamino-1,3,5-triazin-1-ium 3-(prop-2-enoyloxy) propanoate acrylic acid monosolvate monohydrate

NASA Astrophysics Data System (ADS)

Sangeetha, V.; Govindarajan, M.; Kanagathara, N.; Marchewka, M. K.; Drozd, M.; Anbalagan, G.

2013-12-01

New organic crystals of 2,4,6-triamino-1,3,5-triazin-1-ium 3-(prop-2-enoyloxy) propanoate acrylic acid monosolvate monohydrate (MAC) have been obtained from aqueous solution by the slow solvent evaporation method at room temperature. Single crystal X-ray diffraction analysis reveals that the compound crystallises in the triclinic system with centrosymmetric space group P-1. FT-IR and FT-Raman spectra of MAC have been recorded and analyzed. The molecular geometry and vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimization based on density functional theory (DFT) B3LYP method with 6-31G(d,p) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction data. The theoretical results show that the optimized geometry can well reproduce the crystal structure, and the calculated vibrational frequency values show good agreement with experimental values. A study of the electronic properties, such as HOMO and LUMO energies and Molecular electrostatic potential (MEP) were performed. Mulliken charges and NBO charges of the title molecule were also calculated and interpreted. Thermogravimetric analysis has been done to study the thermal behaviour of MAC. The 13C and 1H nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results.

Utilization of group theory in studies of molecular clusters

NASA Astrophysics Data System (ADS)

Ocak, Mahir E.

The structure of the molecular symmetry group of molecular clusters was analyzed and it is shown that the molecular symmetry group of a molecular cluster can be written as direct products and semidirect products of its subgroups. Symmetry adaptation of basis functions in direct product groups and semidirect product groups was considered in general and the sequential symmetry adaptation procedure which is already known for direct product groups was extended to the case of semidirect product groups. By using the sequential symmetry adaptation procedure a new method for calculating the VRT spectra of molecular clusters which is named as Monomer Basis Representation (MBR) method is developed. In the MBR method, calculations starts with a single monomer with the purpose of obtaining an optimized basis for that monomer as a linear combination of some primitive basis functions. Then, an optimized basis for each identical monomer is generated from the optimized basis of this monomer. By using the optimized bases of the monomers, a basis is generated generated for the solution of the full problem, and the VRT spectra of the cluster is obtained by using this basis. Since an optimized basis is used for each monomer which has a much smaller size than the primitive basis from which the optimized bases are generated, the MBR method leads to an exponential optimization in the size of the basis that is required for the calculations. Application of the MBR method has been illustrated by calculating the VRT spectra of water dimer by using the SAPT-5st potential surface of Groenenboom et al. The rest of the calculations are in good agreement with both the original calculations of Groenenboom et al. and also with the experimental results. Comparing the size of the optimized basis with the size of the primitive basis, it can be said that the method works efficiently. Because of its efficiency, the MBR method can be used for studies of clusters bigger than dimers. Thus, MBR method can be used for studying the many-body terms and for deriving accurate potential surfaces.

Molecular structure and vibrational spectra of Irinotecan: a density functional theoretical study.

PubMed

Chinna Babu, P; Sundaraganesan, N; Sudha, S; Aroulmoji, V; Murano, E

2012-12-01

The solid phase FTIR and FT-Raman spectra of Irinotecan have been recorded in the regions 400-4000 and 50-4000 cm(-1), respectively. The spectra were interpreted in terms of fundamentals modes, combination and overtone bands. The structure of the molecule was optimized and the structural characteristics were determined by density functional theory (DFT) using B3LYP method with 6-31G(d) as basis set. The vibrational frequencies were calculated for Irinotecan by DFT method and were compared with the experimental frequencies, which yield good agreement between observed and calculated frequencies. The infrared spectrum was also simulated from the calculated intensities. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis were investigated using theoretical calculations. Copyright © 2012 Elsevier B.V. All rights reserved.

Do homologous thermophilic-mesophilic proteins exhibit similar structures and dynamics at optimal growth temperatures? A molecular dynamics simulation study.

PubMed

Basu, Sohini; Sen, Srikanta

2013-02-25

Structure and dynamics both are known to be important for the activity of a protein. A fundamental question is whether a thermophilic protein and its mesophilic homologue exhibit similar dynamics at their respective optimal growth temperatures. We have addressed this question by performing molecular dynamics (MD) simulations of a natural mesophilic-thermophilic homologue pair at their respective optimal growth temperatures to compare their structural, dynamical, and solvent properties. The MD simulations were done in explicit aqueous solvent under periodic boundary and constant pressure and temperature (CPT) conditions and continued for 10.0 ns using the same protocol for the two proteins, excepting the temperatures. The trajectories were analyzed to compare the properties of the two proteins. Results indicated that the dynamical behaviors of the two proteins at the respective optimal growth temperatures were remarkably similar. For the common residues in the thermophilic protein, the rms fluctuations have a general trend to be slightly higher compared to that in the mesophilic counterpart. Lindemann parameter values indicated that only a few residues exhibited solid-like dynamics while the protein as a whole appeared as a molten globule in each case. Interestingly, the water-water interaction was found to be strikingly similar in spite of the difference in temperatures while, the protein-water interaction was significantly different in the two simulations.

Using FT-IR Spectroscopy to Elucidate the Structures of Ablative Polymers

NASA Technical Reports Server (NTRS)

Fan, Wendy

2011-01-01

The composition and structure of an ablative polymer has a multifaceted influence on its thermal, mechanical and ablative properties. Understanding the molecular level information is critical to the optimization of material performance because it helps to establish correlations with the macroscopic properties of the material, the so-called structure-property relationship. Moreover, accurate information of molecular structures is also essential to predict the thermal decomposition pathways as well as to identify decomposition species that are fundamentally important to modeling work. In this presentation, I will describe the use of infrared transmission spectroscopy (FT-IR) as a convenient tool to aid the discovery and development of thermal protection system materials.

Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

NASA Astrophysics Data System (ADS)

Chung, Pil Seung; Song, Wonyup; Biegler, Lorenz T.; Jhon, Myung S.

2017-05-01

During the operation of hard disk drive (HDD), the perfluoropolyether (PFPE) lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic) and loss (viscous) moduli (G' and G″) by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

Blending Determinism with Evolutionary Computing: Applications to the Calculation of the Molecular Electronic Structure of Polythiophene.

PubMed

Sarkar, Kanchan; Sharma, Rahul; Bhattacharyya, S P

2010-03-09

A density matrix based soft-computing solution to the quantum mechanical problem of computing the molecular electronic structure of fairly long polythiophene (PT) chains is proposed. The soft-computing solution is based on a "random mutation hill climbing" scheme which is modified by blending it with a deterministic method based on a trial single-particle density matrix [P((0))(R)] for the guessed structural parameters (R), which is allowed to evolve under a unitary transformation generated by the Hamiltonian H(R). The Hamiltonian itself changes as the geometrical parameters (R) defining the polythiophene chain undergo mutation. The scale (λ) of the transformation is optimized by making the energy [E(λ)] stationary with respect to λ. The robustness and the performance levels of variants of the algorithm are analyzed and compared with those of other derivative free methods. The method is further tested successfully with optimization of the geometry of bipolaron-doped long PT chains.

[Quantitative structure-gas chromatographic retention relationship of polycyclic aromatic sulfur heterocycles using molecular electronegativity-distance vector].

PubMed

Li, Zhenghua; Cheng, Fansheng; Xia, Zhining

2011-01-01

The chemical structures of 114 polycyclic aromatic sulfur heterocycles (PASHs) have been studied by molecular electronegativity-distance vector (MEDV). The linear relationships between gas chromatographic retention index and the MEDV have been established by a multiple linear regression (MLR) model. The results of variable selection by stepwise multiple regression (SMR) and the powerful predictive abilities of the optimization model appraised by leave-one-out cross-validation showed that the optimization model with the correlation coefficient (R) of 0.994 7 and the cross-validated correlation coefficient (Rcv) of 0.994 0 possessed the best statistical quality. Furthermore, when the 114 PASHs compounds were divided into calibration and test sets in the ratio of 2:1, the statistical analysis showed our models possesses almost equal statistical quality, the very similar regression coefficients and the good robustness. The quantitative structure-retention relationship (QSRR) model established may provide a convenient and powerful method for predicting the gas chromatographic retention of PASHs.

Quantum chemical investigations on the molecular structure, FTIR, UV-Vis and HOMO-LUMO analysis of 15-16-epoxy-7b, 9a dihydroxylabdane 13(16), 14-dien-6-one

NASA Astrophysics Data System (ADS)

Uppal, Anshul; Pathania, Kamni; Khajuria, Yugal

2018-05-01

The structural, spectroscopic (Fourier Transform Infrared (FT-IR), Ultra-Violet Visible (UV-VIS)) and thermodynamic properties of 15, 16-epoxy-7b, 9a dihydroxylabdane-13(16), 14-dien-6-one were studied by using both experimental techniques and theoretical methods. The FTIR spectrum of the title compound was recorded in the spectral range 4000-400 cm-1. The UV-VIS spectrum was measured in the spectral range 190-800 nm. The quantum chemistry calculations have been performed to compute optimized geometry, molecular parameters, vibrational frequencies along with intensities using Hartree Fock (HF) theory and Density Functional Theory (DFT) with 6-31G basis set. The calculated HOMO-LUMO energies show that the charge transfer occurs within the molecule. The temperature dependence of the thermodynamic properties like heat capacity, entropy and enthalpy of the optimized structure were obtained. Finally, a comparison between the experimental data and the calculated results presented a good agreement.

Sequence-structure correlations in silk: Poly-Ala repeat of N. clavipes MaSp1 is naturally optimized at a critical length scale.

PubMed

Bratzel, Graham; Buehler, Markus J

2012-03-01

Spider silk is a self-assembling biopolymer that outperforms many known materials in terms of its mechanical performance despite being constructed from simple and inferior building blocks. While experimental studies have shown that the molecular structure of silk has a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies in particular under variations of genetic sequences have been reported. Here we report atomistic-level structures of the MaSp1 protein from the Nephila Clavipes spider dragline silk sequence, obtained using an in silico approach based on replica exchange molecular dynamics (REMD) and explicit water molecular dynamics. We apply this method to study the effects of a systematic variation of the poly-alanine repeat lengths, a parameter controlled by the genetic makeup of silk, on the resulting molecular structure of silk at the nanoscale. Confirming earlier experimental and computational work, a structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly β-sheet crystal domains while disorderly regions are formed by glycine-rich repeats that consist of 3(10)-helix type structures and β-turns. Our predictions are directly validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots combined with an analysis of the secondary structure content. The key result of our study is our finding of a strong dependence of the resulting silk nanostructure depending on the poly-alanine length. We observe that the wildtype poly-alanine repeat length of six residues defines a critical minimum length that consistently results in clearly defined β-sheet nanocrystals. For poly-alanine lengths below six, the β-sheet nanocrystals are not well-defined or not visible at all, while for poly-alanine lengths at and above six, the characteristic nanocomposite structure of silk emerges with no significant improvement of the quality of the β-sheet nanocrystal geometry. We present a simple biophysical model that explains these computational observations based on the mechanistic insight gained from the molecular simulations. Our findings set the stage for understanding how variations in the spidroin sequence can be used to engineer the structure and thereby functional properties of this biological superfiber, and present a design strategy for the genetic optimization of spidroins for enhanced mechanical properties. The approach used here may also find application in the design of other self-assembled molecular structures and fibers and in particular biologically inspired or completely synthetic systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

A novel membrane-based process to isolate peroxidase from horseradish roots: optimization of operating parameters.

PubMed

Liu, Jianguo; Yang, Bo; Chen, Changzhen

2013-02-01

The optimization of operating parameters for the isolation of peroxidase from horseradish (Armoracia rusticana) roots with ultrafiltration (UF) technology was systemically studied. The effects of UF operating conditions on the transmission of proteins were quantified using the parameter scanning UF. These conditions included solution pH, ionic strength, stirring speed and permeate flux. Under optimized conditions, the purity of horseradish peroxidase (HRP) obtained was greater than 84 % after a two-stage UF process and the recovery of HRP from the feedstock was close to 90 %. The resulting peroxidase product was then analysed by isoelectric focusing, SDS-PAGE and circular dichroism, to confirm its isoelectric point, molecular weight and molecular secondary structure. The effects of calcium ion on HRP specific activities were also experimentally determined.

Ternary AlGaN Alloys with High Al Content and Enhanced Compositional Homogeneity Grown by Plasma-Assisted Molecular Beam Epitaxy

NASA Astrophysics Data System (ADS)

Fellmann, Vincent; Jaffrennou, Périne; Sam-Giao, Diane; Gayral, Bruno; Lorenz, Katharina; Alves, Eduardo; Daudin, Bruno

2011-03-01

We have studied the influence of III/N flux ratio and growth temperature on structural and optical properties of high Al-content, around 50-60%, AlGaN alloy layers grown by plasma-assisted molecular beam epitaxy. In a first part, based on structural analysis by Rutherford Backscattering Spectroscopy, we establish that a III/N flux ratio slightly above 1 produces layers with low amount of structural defects. In a second part, we study the effect of growth temperature on structural and optical properties of layers grown with previously determined optimal III/N flux ratio. We find that optimal growth temperatures for Al0.50Ga0.50N layers with compositional homogeneity related with narrow UV photoluminescence properties are in the low temperature range for growing GaN layers, i.e., 650-680 °C. We propose that lowering Ga adatom diffusion on the surface favors random incorporation of both Ga and Al adatoms on wurtzite crystallographic sites leading to the formation of an homogeneous alloy.

Optimal descriptor as a translator of eclectic information into the prediction of membrane damage by means of various TiO(2) nanoparticles.

PubMed

Toropova, Alla P; Toropov, Andrey A

2013-11-01

The increasing use of nanomaterials incorporated into consumer products leads to the need for developing approaches to establish "quantitative structure-activity relationships" (QSARs) for various nanomaterials. However, the molecular structure as rule is not available for nanomaterials at least in its classic meaning. An possible alternative of classic QSAR (based on the molecular structure) is the using of data on physicochemical features of TiO(2) nanoparticles. The damage to cellular membranes (units L(-1)) by means of various TiO(2) nanoparticles is examined as the endpoint. Copyright © 2013 Elsevier Ltd. All rights reserved.

SCRIPDB: a portal for easy access to syntheses, chemicals and reactions in patents

PubMed Central

Heifets, Abraham; Jurisica, Igor

2012-01-01

The patent literature is a rich catalog of biologically relevant chemicals; many public and commercial molecular databases contain the structures disclosed in patent claims. However, patents are an equally rich source of metadata about bioactive molecules, including mechanism of action, disease class, homologous experimental series, structural alternatives, or the synthetic pathways used to produce molecules of interest. Unfortunately, this metadata is discarded when chemical structures are deposited separately in databases. SCRIPDB is a chemical structure database designed to make this metadata accessible. SCRIPDB provides the full original patent text, reactions and relationships described within any individual patent, in addition to the molecular files common to structural databases. We discuss how such information is valuable in medical text mining, chemical image analysis, reaction extraction and in silico pharmaceutical lead optimization. SCRIPDB may be searched by exact chemical structure, substructure or molecular similarity and the results may be restricted to patents describing synthetic routes. SCRIPDB is available at http://dcv.uhnres.utoronto.ca/SCRIPDB. PMID:22067445

Cationic lipids: molecular structure/ transfection activity relationships and interactions with biomembranes.

PubMed

Koynova, Rumiana; Tenchov, Boris

2010-01-01

Abstract Synthetic cationic lipids, which form complexes (lipoplexes) with polyanionic DNA, are presently the most widely used constituents of nonviral gene carriers. A large number of cationic amphiphiles have been synthesized and tested in transfection studies. However, due to the complexity of the transfection pathway, no general schemes have emerged for correlating the cationic lipid chemistry with their transfection efficacy and the approaches for optimizing their molecular structures are still largely empirical. Here we summarize data on the relationships between transfection activity and cationic lipid molecular structure and demonstrate that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure. A number of examples, including a large series of cationic phosphatidylcholine derivatives, show that optimum transfection is displayed by lipids with chain length of approximately 14 carbon atoms and that the transfection efficiency strongly increases with increase of chain unsaturation, specifically upon replacement of saturated with monounsaturated chains.

Inverse design of bulk morphologies in block copolymers using particle swarm optimization

NASA Astrophysics Data System (ADS)

Khadilkar, Mihir; Delaney, Kris; Fredrickson, Glenn

Multiblock polymers are a versatile platform for creating a large range of nanostructured materials with novel morphologies and properties. However, achieving desired structures or property combinations is difficult due to a vast design space comprised of parameters including monomer species, block sequence, block molecular weights and dispersity, copolymer architecture, and binary interaction parameters. Navigating through such vast design spaces to achieve an optimal formulation for a target structure or property set requires an efficient global optimization tool wrapped around a forward simulation technique such as self-consistent field theory (SCFT). We report on such an inverse design strategy utilizing particle swarm optimization (PSO) as the global optimizer and SCFT as the forward prediction engine. To avoid metastable states in forward prediction, we utilize pseudo-spectral variable cell SCFT initiated from a library of defect free seeds of known block copolymer morphologies. We demonstrate that our approach allows for robust identification of block copolymers and copolymer alloys that self-assemble into a targeted structure, optimizing parameters such as block fractions, blend fractions, and Flory chi parameters.

WIWS: a protein structure bioinformatics Web service collection.

PubMed

Hekkelman, M L; Te Beek, T A H; Pettifer, S R; Thorne, D; Attwood, T K; Vriend, G

2010-07-01

The WHAT IF molecular-modelling and drug design program is widely distributed in the world of protein structure bioinformatics. Although originally designed as an interactive application, its highly modular design and inbuilt control language have recently enabled its deployment as a collection of programmatically accessible web services. We report here a collection of WHAT IF-based protein structure bioinformatics web services: these relate to structure quality, the use of symmetry in crystal structures, structure correction and optimization, adding hydrogens and optimizing hydrogen bonds and a series of geometric calculations. The freely accessible web services are based on the industry standard WS-I profile and the EMBRACE technical guidelines, and are available via both REST and SOAP paradigms. The web services run on a dedicated computational cluster; their function and availability is monitored daily.

Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library.

PubMed

Ma, Dik-Lung; Chan, Daniel Shiu-Hin; Wei, Guo; Zhong, Hai-Jing; Yang, Hui; Leung, Lai To; Gullen, Elizabeth A; Chiu, Pauline; Cheng, Yung-Chi; Leung, Chung-Hang

2014-11-21

Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.

Insights from molecular modeling and dynamics simulation of pathogen resistance (R) protein from brinjal.

PubMed

Shrivastava, Dipty; Nain, Vikrant; Sahi, Shakti; Verma, Anju; Sharma, Priyanka; Sharma, Prakash Chand; Kumar, Polumetla Ananda

2011-01-22

Resistance (R) protein recognizes molecular signature of pathogen infection and activates downstream hypersensitive response signalling in plants. R protein works as a molecular switch for pathogen defence signalling and represent one of the largest plant gene family. Hence, understanding molecular structure and function of R proteins has been of paramount importance for plant biologists. The present study is aimed at predicting structure of R proteins signalling domains (CC-NBS) by creating a homology model, refining and optimising the model by molecular dynamics simulation and comparing ADP and ATP binding. Based on sequence similarity with proteins of known structures, CC-NBS domains were initially modelled using CED- 4 (cell death abnormality protein) and APAF-1 (apoptotic protease activating factor) as multiple templates. The final CC-NBS structural model was built and optimized by molecular dynamic simulation for 5 nanoseconds (ns). Docking of ADP and ATP at active site shows that both ligand bind specifically with same residues and with minor difference (1 Kcal/mol) in binding energy. Sharing of binding site by ADP and ATP and low difference in their binding site makes CC-NBS suitable for working as molecular switch. Furthermore, structural superimposition elucidate that CC-NBS and CARD (caspase recruitment domains) domain of CED-4 have low RMSD value of 0.9 A° Availability of 3D structural model for both CC and NBS domains will . help in getting deeper insight in these pathogen defence genes.

Conformational, vibrational spectroscopic and quantum chemical studies on 5-methoxyindole-3-carboxaldehyde: A DFT approach

NASA Astrophysics Data System (ADS)

Jeyaseelan, S. Christopher; Hussain, Shamima; Premkumar, R.; Rekha, T. N.; Benial, A. Milton Franklin

2018-04-01

Indole and its derivatives are considered as good ligands for various disease causing proteins in human because of presence of the single nitrogen atom. In the present study, the potential energy surface scan was performed for the most stable molecular structure of the 5-Methoxyindole-3-carboxaldehyde (MICA) molecule. The most stable molecular structure was optimized by DFT/B3LYP method with 6-311G++ (d, p) basis set using Gaussian 09 program package. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculations using VEDA 4.0 program. The Frontier molecular orbitals analysis was performed and related molecular propertieswere calculated. The possible electrophilic and nucleophilic reactive sites of the molecule were studied using molecular electrostatic potential analysis, which confirms the bioactivity of the molecule. The natural bond orbital analysis was also performed to confirm the bioactivity of the title molecule.

Concept of combinatorial de novo design of drug-like molecules by particle swarm optimization.

PubMed

Hartenfeller, Markus; Proschak, Ewgenij; Schüller, Andreas; Schneider, Gisbert

2008-07-01

We present a fast stochastic optimization algorithm for fragment-based molecular de novo design (COLIBREE, Combinatorial Library Breeding). The search strategy is based on a discrete version of particle swarm optimization. Molecules are represented by a scaffold, which remains constant during optimization, and variable linkers and side chains. Different linkers represent virtual chemical reactions. Side-chain building blocks were obtained from pseudo-retrosynthetic dissection of large compound databases. Here, ligand-based design was performed using chemically advanced template search (CATS) topological pharmacophore similarity to reference ligands as fitness function. A weighting scheme was included for particle swarm optimization-based molecular design, which permits the use of many reference ligands and allows for positive and negative design to be performed simultaneously. In a case study, the approach was applied to the de novo design of potential peroxisome proliferator-activated receptor subtype-selective agonists. The results demonstrate the ability of the technique to cope with large combinatorial chemistry spaces and its applicability to focused library design. The technique was able to perform exploitation of a known scheme and at the same time explorative search for novel ligands within the framework of a given molecular core structure. It thereby represents a practical solution for compound screening in the early hit and lead finding phase of a drug discovery project.

Structure change of β-hairpin induced by turn optimization: an enhanced sampling molecular dynamics simulation study.

PubMed

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

2011-12-21

Our previous study showed that for the tested polypeptides which have similar β-hairpin structures but different sequences, their folding free energy pathways are dominantly determined by the turn conformational propensity. In this study, we study how the turn conformational propensity affects the structure of hairpins. The folding of two mutants of GB1p peptide (GB1m2 and GB1m3), which have the optimized turn sequence ((6)DDATK(11)T → (6)NPATG(11)K) with native structures unsolved, were simulated using integrated tempering sampling molecular dynamics simulations and the predicted stable structures were compared to wild-type GB1p. It was observed that the turn optimization of GB1p generates a more favored 5-residue type I(') turn in addition to the 6-residue type I turn in wild-type GB1p. As a result two distinctly different hairpin structures are formed corresponding to the "misfolded" (M) and the "folded" (F) states. M state is a one-residue-shifted asymmetric β-hairpin structure whereas F state has the similar symmetric hairpin structure as wild-type GB1p. The formation of the favored type I(') turn has a small free energy barrier and leads to the shifted β-hairpin structure, following the modified "zipping" model. The presence of disfavored type I turn structure makes the folding of a β-hairpin consistent with the "hydrophobic-core-centric" model. On the other hand, the folding simulations on other two GB1p mutants (GB1r1 and GBr2), which have the position of the hydrophobic core cluster further away from the turn compared to wild-type GB1p, showed that moving the hydrophobic core cluster away from the turn region destabilizes but does not change the hairpin structure. Therefore, the present study showed that the turn conformational propensity is a key factor in affecting not only the folding pathways but also the stable structure of β-hairpins, and the turn conformational change induced by the turn optimization leads to significant changes of β-hairpin structure.

A consistent methodology for optimal shape design of graphene sheets to maximize their fundamental frequencies considering topological defects

NASA Astrophysics Data System (ADS)

Shi, Jin-Xing; Ohmura, Keiichiro; Shimoda, Masatoshi; Lei, Xiao-Wen

2018-07-01

In recent years, shape design of graphene sheets (GSs) by introducing topological defects for enhancing their mechanical behaviors has attracted the attention of scholars. In the present work, we propose a consistent methodology for optimal shape design of GSs using a combination of the molecular mechanics (MM) method, the non-parametric shape optimization method, the phase field crystal (PFC) method, Voronoi tessellation, and molecular dynamics (MD) simulation to maximize their fundamental frequencies. At first, we model GSs as continuum frame models using a link between the MM method and continuum mechanics. Then, we carry out optimal shape design of GSs in fundamental frequency maximization problem based on a developed shape optimization method for frames. However, the obtained optimal shapes of GSs only consisting of hexagonal carbon rings are unstable that do not satisfy the principle of least action, so we relocate carbon atoms on the optimal shapes by introducing topological defects using the PFC method and Voronoi tessellation. At last, we perform the structural relaxation through MD simulation to determine the final optimal shapes of GSs. We design two examples of GSs and the optimal results show that the fundamental frequencies of GSs can be significantly enhanced according to the optimal shape design methodology.

Guiding lead optimization with GPCR structure modeling and molecular dynamics.

PubMed

Heifetz, Alexander; James, Tim; Morao, Inaki; Bodkin, Michael J; Biggin, Philip C

2016-10-01

G-protein coupled receptor (GPCR) modeling approaches are widely used in the hit-to-lead and lead optimization stages of drug discovery. Modern protocols that involve molecular dynamics simulation can address key issues such as the free energy of binding (affinity), ligand-induced GPCR flexibility, ligand binding kinetics, conserved water positions and their role in ligand binding and the effects of mutations. The goals of these calculations are to predict the structures of the complexes between existing ligands and their receptors, to understand the key interactions and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this review we present a brief survey of various computational approaches illustrated through a hierarchical GPCR modeling protocol and its prospective application in three industrial drug discovery projects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elucidating the Solvation Structure and Dynamics of Lithium Polysulfides Resulting from Competitive Salt and Solvent Interactions

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

Rajput, Nav Nidhi; Murugesan, Vijayakumar; Shin, Yongwoo

2017-04-10

Fundamental molecular level understanding of functional properties of liquid solutions provides an important basis for designing optimized electrolytes for numerous applica-tions. In particular, exhaustive knowledge of solvation structure, stability and transport properties is critical for developing stable electrolytes for fast charging and high energy density next-generation energy storage systems. Here we report the correlation between solubility, solvation structure and translational dynamics of a lithium salt (Li-TFSI) and polysulfides species using well-benchmarked classical molecular dynamics simulations combined with nuclear magnetic resonance (NMR). It is observed that the polysulfide chain length has a significant effect on the ion-ion and ion-solvent interaction asmore » well as on the diffusion coefficient of the ionic species in solution. In particular, extensive cluster formation is observed in lower order poly-sulfides (Sx2-; x≤4), whereas the longer polysulfides (Sx2-; x>4) show high solubility and slow dynamics in the solu-tion. It is observed that optimal solvent/salt ratio is essen-tial to control the solubility and conductivity as the addi-tion of Li salt increases the solubility but decreases the mo-bility of the ionic species. This work provides a coupled theoretical and experimental study of bulk solvation struc-ture and transport properties of multi-component electro-lyte systems, yielding design metrics for developing optimal electrolytes with improved stability and solubility.« less

Integration of Molecular Dynamics Based Predictions into the Optimization of De Novo Protein Designs: Limitations and Benefits.

PubMed

Carvalho, Henrique F; Barbosa, Arménio J M; Roque, Ana C A; Iranzo, Olga; Branco, Ricardo J F

2017-01-01

Recent advances in de novo protein design have gained considerable insight from the intrinsic dynamics of proteins, based on the integration of molecular dynamics simulations protocols on the state-of-the-art de novo protein design protocols used nowadays. With this protocol we illustrate how to set up and run a molecular dynamics simulation followed by a functional protein dynamics analysis. New users will be introduced to some useful open-source computational tools, including the GROMACS molecular dynamics simulation software package and ProDy for protein structural dynamics analysis.

Molecular structure, FT-IR, vibrational assignments, HOMO-LUMO, MEP, NBO analysis and molecular docking study of ethyl-6-(4-chlorophenyl)-4-(4-fluorophenyl)-2-oxocyclohex-3-ene-1-carboxylate.

PubMed

Sheena Mary, Y; Yohannan Panicker, C; Sapnakumari, M; Narayana, B; Sarojini, B K; Al-Saadi, Abdulaziz A; Van Alsenoy, Christian; War, Javeed Ahmad

2015-03-05

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of ethyl-6-(4-chlorophenyl)-4-(4-fluoro-phenyl)-2-oxocyclohex-3-ene-1-carboxylate have been investigated experimentally and theoretically using Gaussian09 software. The title compound was optimized using the HF and DFT levels of theory. The geometrical parameters are in agreement with the XRD data. The stability of the molecule has been analyzed by NBO analysis. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular electrostatic potential was performed by the DFT method. As can be seen from the MEP map of the title compound, regions having the negative potential are over the electro negative atoms, the region having the positive potential are over the phenyl rings and the remaining species are surrounded by zero potential. First hyperpolarizability is calculated in order to find its role in non linear optics. The title compound binds at the active sites of both CypD and β-secretase and the molecular docking results draw the conclusion that the compound might exhibit β-secretase inhibitory activity which could be utilized for development of new anti-alzheimeric drugs with mild CypD inhibitory activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Mutagenicity, anticancer activity and blood brain barrier: similarity and dissimilarity of molecular alerts.

PubMed

Toropov, Andrey A; Toropova, Alla P; Benfenati, Emilio; Salmona, Mario

2018-06-01

The aim of the present work is an attempt to define computable measure of similarity between different endpoints. The similarity of structural alerts of different biochemical endpoints can be used to solve tasks of medicinal chemistry. Optimal descriptors are a tool to build up models for different endpoints. The optimal descriptor is calculated with simplified molecular input-line entry system (SMILES). A group of elements (single symbol or pair of symbols) can represent any SMILES. Each element of SMILES can be represented by so-called correlation weight i.e. coefficient that should be used to calculate descriptor. Numerical data on the correlation weights are calculated by the Monte Carlo method, i.e. by optimization procedure, which gives maximal correlation coefficient between the optimal descriptor and endpoint for the training set. Statistically stable correlation weights observed in several runs of the optimization can be examined as structural alerts, which are promoters of the increase or the decrease of a biochemical activity of a substance. Having data on several runs of the optimization correlation weights, one can extract list of promoters of increase and list of promoters of decrease for an endpoint. The study of similarity and dissimilarity of the above lists has been carried out for the following pairs of endpoints: (i) mutagenicity and anticancer activity; (ii) mutagenicity and blood brain barrier; and (iii) blood brain barrier and anticancer activity. The computational experiment confirms that similarity and dissimilarity for pairs of endpoints can be measured.

Covalent addition of chitosan to graphene sheets: Density functional theory explorations of quadrupole coupling constants

NASA Astrophysics Data System (ADS)

Mokhtari, Ali; Harismah, Kun; Mirzaei, Mahmoud

2015-12-01

Density functional theory (DFT) calculations have been performed to detect the stabilities and properties of chitosan-functionalized graphene and graphene-oxide structures (G-Chit and GO-Chit). The model systems with two different sizes of sheets have been optimized and the molecular and atomic properties have been evaluated for them. The results indicated that investigated G-Chit and GO-Chit structures could be considered as stable structures but with different properties. The properties for GO and GO-Chit structures are almost similar; however, they are different from the original G and G-Chit structures. The results also indicated that the properties could be also size-dependent, in which different molecular and atomic properties have been observed for the investigate G sheets.

Structural, spectral, NLO and MEP analysis of the [MgO2Ti2(OPri)6], [MgO2Ti2(OPri)2(acac)4] and [MgO2Ti2(OPri)2(bzac)4] by DFT method

NASA Astrophysics Data System (ADS)

Sayin, Koray; Karakaş, Duran

2015-06-01

Quantum chemical calculations are performed on [MgO2Ti2(OPri)6] and [MgO2Ti2(OPri)2(L)4] complexes. L is acetylacetonate (acac) and benzoylacetonate (bzac) anion. The crystal structures of these complexes have not been obtained as experimentally but optimized structures of these complexes are obtained as theoretically in this study. Universal force field (UFF) and DFT/B3LYP method are used to obtain optimized structures. Theoretical spectral analysis (IR, 1H and 13C NMR) is compared with their experimental values. A good agreement is found between experimental and theoretical spectral analysis. These results mean that the optimized structures of mentioned complexes are appropriate. Additionally, the active sites of mentioned complexes are determined by molecular electrostatic potential (MEP) diagrams and non-linear optical (NLO) properties are investigated.

Combination of molecular, morphological, and interfacial engineering to achieve highly efficient and stable plastic solar cells.

PubMed

Chang, Chih-Yu; Cheng, Yen-Ju; Hung, Shih-Hsiu; Wu, Jhong-Sian; Kao, Wei-Shun; Lee, Chia-Hao; Hsu, Chain-Shu

2012-01-24

A flexible solar device showing exceptional air and mechanical stability is produced by simultaneously optimizing molecular structure, active layer morphology, and interface characteristics. The PFDCTBT-C8-based devices with inverted architecture exhibited excellent power conversion efficiencies of 7.0% and 6.0% on glass and flexible substrates, respectively. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DFT calculation and vibrational spectroscopic studies of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine

NASA Astrophysics Data System (ADS)

Premkumar, S.; Jawahar, A.; Mathavan, T.; Kumara Dhas, M.; Sathe, V. G.; Milton Franklin Benial, A.

2014-08-01

The molecular structure of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine (BABP) was optimized by the DFT/B3LYP method with 6-311G (d,p), 6-311++G (d,p) and cc-pVTZ basis sets using the Gaussian 09 program. The most stable optimized structure of the molecule was predicted by the DFT/B3LYP method with cc-pVTZ basis set. The vibrational frequencies, Mulliken atomic charge distribution, frontier molecular orbitals and thermodynamical parameters were calculated. These calculations were done at the ground state energy level of BABP without applying any constraint on the potential energy surface. The vibrational spectra were experimentally recorded using Fourier Transform-Infrared (FT-IR) and micro-Raman spectrometer. The computed vibrational frequencies were scaled by scale factors to yield a good agreement with observed experimental vibrational frequencies. The complete theoretically calculated and experimentally observed vibrational frequencies were assigned on the basis of Potential Energy Distribution (PED) calculation using the VEDA 4.0 program. The vibrational modes assignments were performed by using the animation option of GaussView 05 graphical interface for Gaussian program. The Mulliken atomic charge distribution was calculated for BABP molecule. The molecular reactivity and stability of BABP were also studied by frontier molecular orbitals (FMOs) analysis.

Structural, vibrational and theoretical studies of anilinium trichloroacetate: New hydrogen bonded molecular crystal with nonlinear optical properties

NASA Astrophysics Data System (ADS)

Tanak, H.; Pawlus, K.; Marchewka, M. K.; Pietraszko, A.

2014-01-01

In this work, we report a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of the potential nonlinear optical (NLO) material anilinium trichloroacetate. The FT-IR and FT-Raman spectra of the compound have been recorded together between 4000-80 cm-1 and 3600-80 cm-1 regions, respectively. The compound crystallizes in the noncentrosymmetric space group of monoclinic system. The optimized molecular structure, vibrational wavenumbers, IR intensities and Raman activities have been calculated by using density functional method (B3LYP) with 6-311++G(d,p) as higher basis set. The obtained vibrational wavenumbers and optimized geometric parameters were seen to be in good agreement with the experimental data. DSC measurements on powder samples do not indicate clearly on the occurrence of phase transitions in the temperature 113-293 K. The Kurtz and Perry powder reflection technique appeared to be very effective in studies of second-order nonlinear optical properties of the molecule. The non-linear optical properties are also addressed theoretically. The predicted NLO properties of the title compound are much greater than ones of urea. In addition, DFT calculations of the title compound, molecular electrostatic potential, frontier orbitals and thermodynamic properties were also performed at 6-311++G(d,p) level of theory. For title crystal the SHG efficiency was estimated by Kurtz-Perry method to be deff = 0.70 deff (KDP).

Structural, vibrational and theoretical studies of anilinium trichloroacetate: new hydrogen bonded molecular crystal with nonlinear optical properties.

PubMed

Tanak, H; Pawlus, K; Marchewka, M K; Pietraszko, A

2014-01-24

In this work, we report a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of the potential nonlinear optical (NLO) material anilinium trichloroacetate. The FT-IR and FT-Raman spectra of the compound have been recorded together between 4000-80 cm(-1) and 3600-80 cm(-1) regions, respectively. The compound crystallizes in the noncentrosymmetric space group of monoclinic system. The optimized molecular structure, vibrational wavenumbers, IR intensities and Raman activities have been calculated by using density functional method (B3LYP) with 6-311++G(d,p) as higher basis set. The obtained vibrational wavenumbers and optimized geometric parameters were seen to be in good agreement with the experimental data. DSC measurements on powder samples do not indicate clearly on the occurrence of phase transitions in the temperature 113-293 K. The Kurtz and Perry powder reflection technique appeared to be very effective in studies of second-order nonlinear optical properties of the molecule. The non-linear optical properties are also addressed theoretically. The predicted NLO properties of the title compound are much greater than ones of urea. In addition, DFT calculations of the title compound, molecular electrostatic potential, frontier orbitals and thermodynamic properties were also performed at 6-311++G(d,p) level of theory. For title crystal the SHG efficiency was estimated by Kurtz-Perry method to be d(eff)=0.70 d(eff) (KDP). Copyright © 2013 Elsevier B.V. All rights reserved.

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

PubMed

Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

2018-01-01

This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

Structural and electronic properties of carbon nanotube-reinforced epoxy resins.

PubMed

Suggs, Kelvin; Wang, Xiao-Qian

2010-03-01

Nanocomposites of cured epoxy resin reinforced by single-walled carbon nanotubes exhibit a plethora of interesting behaviors at the molecular level. We have employed a combination of force-field-based molecular mechanics and first-principles calculations to study the corresponding binding and charge-transfer behavior. The simulation study of various nanotube species and curing agent configurations provides insight into the optimal structures in lieu of interfacial stability. An analysis of charge distributions of the epoxy functionalized semiconducting and metallic tubes reveals distinct level hybridizations. The implications of these results for understanding dispersion mechanism and future nano reinforced composite developments are discussed.

Optimizing isotope substitution in graphene for thermal conductivity minimization by genetic algorithm driven molecular simulations

NASA Astrophysics Data System (ADS)

Davies, Michael; Ganapathysubramanian, Baskar; Balasubramanian, Ganesh

2017-03-01

We present results from a computational framework integrating genetic algorithm and molecular dynamics simulations to systematically design isotope engineered graphene structures for reduced thermal conductivity. In addition to the effect of mass disorder, our results reveal the importance of atomic distribution on thermal conductivity for the same isotopic concentration. Distinct groups of isotope-substituted graphene sheets are identified based on the atomic composition and distribution. Our results show that in structures with equiatomic compositions, the enhanced scattering by lattice vibrations results in lower thermal conductivities due to the absence of isotopic clusters.

An in-silico walker

NASA Astrophysics Data System (ADS)

Xiao, Qiran; Chen, Yanping; Bereau, Tristan; Shi, Yunfeng

2016-08-01

The paradox of biomimetic research is to perform bio-functionality, usually associated with sophisticated structures optimized by nature, with minimal structural complexity for the ease of fabrication. Here we show that a three-particle trimer can exhibit kinesin-like autonomous walk on a track via reactive molecular dynamics simulations. The autonomous motion is due to imbalanced transitions resulting from exothermic catalytic reactions, and the spatial asymmetry from the track. This molecular design can be realized by reproducing the particle-particle interactions in functionalized nano- or colloidal particles. Our results open up the possibility of fabricating bio-mimetic nano-systems in a minimalist approach.

Molecular adsorption and multilayer growth of pentacene on Cu(100):Layer structure and energetics

NASA Astrophysics Data System (ADS)

Satta, M.; Iacobucci, S.; Larciprete, R.

2007-04-01

We used the partial charge tight binding method to perform a full structure optimization to determine equilibrium adsorption geometries, energetics, and local charge redistribution for molecular adsorption and multilayer growth of pentacene on Cu(100). We found that single molecule adsorption induces only a localized perturbation of the metal lattice which is limited to the topmost layers. At saturation coverage four stable topologies (Brick, Wave, Lines and Zigzag) were identified, all based on pentacene molecules lying flat on the metal surface and with the central phenyl ring adsorbed in top position. Only two (Brick and Wave) out of the four structures are able to sustain multilayer growth. In both cases, assembling beyond the second layer corresponds to a transition from the flat to a tilted geometry, in which the pentacenes adopt a face-plane-face arrangement leading to a herringbone structure. The energetics of the different structure are reported as a function of the molecular number density of the pentacene multilayer by calculating cohesive, stress, and electrostatic energies. The dominant tilted molecular orientation in the pentacene multilayer is in agreement with the average tilt angle of 65° between the molecular plane and the Cu surface derived by near edge x-ray absorption spectroscopy of a four monolayer pentacene film deposited on Cu(100).

Fast automatic segmentation of anatomical structures in x-ray computed tomography images to improve fluorescence molecular tomography reconstruction.

PubMed

Freyer, Marcus; Ale, Angelique; Schulz, Ralf B; Zientkowska, Marta; Ntziachristos, Vasilis; Englmeier, Karl-Hans

2010-01-01

The recent development of hybrid imaging scanners that integrate fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) allows the utilization of x-ray information as image priors for improving optical tomography reconstruction. To fully capitalize on this capacity, we consider a framework for the automatic and fast detection of different anatomic structures in murine XCT images. To accurately differentiate between different structures such as bone, lung, and heart, a combination of image processing steps including thresholding, seed growing, and signal detection are found to offer optimal segmentation performance. The algorithm and its utilization in an inverse FMT scheme that uses priors is demonstrated on mouse images.

Component-based integration of chemistry and optimization software.

PubMed

Kenny, Joseph P; Benson, Steven J; Alexeev, Yuri; Sarich, Jason; Janssen, Curtis L; McInnes, Lois Curfman; Krishnan, Manojkumar; Nieplocha, Jarek; Jurrus, Elizabeth; Fahlstrom, Carl; Windus, Theresa L

2004-11-15

Typical scientific software designs make rigid assumptions regarding programming language and data structures, frustrating software interoperability and scientific collaboration. Component-based software engineering is an emerging approach to managing the increasing complexity of scientific software. Component technology facilitates code interoperability and reuse. Through the adoption of methodology and tools developed by the Common Component Architecture Forum, we have developed a component architecture for molecular structure optimization. Using the NWChem and Massively Parallel Quantum Chemistry packages, we have produced chemistry components that provide capacity for energy and energy derivative evaluation. We have constructed geometry optimization applications by integrating the Toolkit for Advanced Optimization, Portable Extensible Toolkit for Scientific Computation, and Global Arrays packages, which provide optimization and linear algebra capabilities. We present a brief overview of the component development process and a description of abstract interfaces for chemical optimizations. The components conforming to these abstract interfaces allow the construction of applications using different chemistry and mathematics packages interchangeably. Initial numerical results for the component software demonstrate good performance, and highlight potential research enabled by this platform.

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

Lee, Jongbok; Li, Huanbin; Kalin, Alexander J.

Well-defined, fused-ring aromatic oligomers represent promising candidates for the fundamental understanding and application of advanced carbon-rich materials, though bottom-up synthesis and structure–property correlation of these compounds remain challenging. In this work, an efficient synthetic route was employed to construct extended benzo[k]tetraphene-derived oligomers with up to 13 fused rings. The molecular and electronic structures of these compounds were clearly elucidated. Precise correlation of molecular sizes and crystallization dynamics was established, thus demonstrating the pivotal balance between intermolecular interaction and molecular mobility for optimized processing of highly ordered solids of these extended conjugated molecules.

Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

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

Yu,P.

2007-01-01

The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities) in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behaviormore » and nutrient utilization and availability. The emphasis of this review was on (1) using the newly advanced synchrotron technology (S-FTIR) as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2) revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3) prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4) obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.« less

Thermodynamic metrics and optimal paths.

PubMed

Sivak, David A; Crooks, Gavin E

2012-05-11

A fundamental problem in modern thermodynamics is how a molecular-scale machine performs useful work, while operating away from thermal equilibrium without excessive dissipation. To this end, we derive a friction tensor that induces a Riemannian manifold on the space of thermodynamic states. Within the linear-response regime, this metric structure controls the dissipation of finite-time transformations, and bestows optimal protocols with many useful properties. We discuss the connection to the existing thermodynamic length formalism, and demonstrate the utility of this metric by solving for optimal control parameter protocols in a simple nonequilibrium model.

Modulated structure and molecular dissociation of solid chlorine at high pressures

NASA Astrophysics Data System (ADS)

Li, Peifang; Gao, Guoying; Ma, Yanming

2012-08-01

Among diatomic molecular halogen solids, high pressure structures of solid chlorine (Cl2) remain elusive and least studied. We here report first-principles structural search on solid Cl2 at high pressures through our developed particle-swarm optimization algorithm. We successfully reproduced the known molecular Cmca phase (phase I) at low pressure and found that it remains stable up to a high pressure 142 GPa. At 150 GPa, our structural searches identified several energetically competitive, structurally similar, and modulated structures. Analysis of the structural results and their similarity with those in solid Br2 and I2, it was suggested that solid Cl2 adopts an incommensurate modulated structure with a modulation wave close to 2/7 in a narrow pressure range 142-157 GPa. Eventually, our simulations at >157 GPa were able to predict the molecular dissociation of solid Cl2 into monatomic phases having body centered orthorhombic (bco) and face-centered cubic (fcc) structures, respectively. One unique monatomic structural feature of solid Cl2 is the absence of intermediate body centered tetragonal (bct) structure during the bco → fcc transition, which however has been observed or theoretically predicted in solid Br2 and I2. Electron-phonon coupling calculations revealed that solid Cl2 becomes superconductors within bco and fcc phases possessing a highest superconducting temperature of 13.03 K at 380 GPa. We further probed the molecular Cmca → incommensurate phase transition mechanism and found that the softening of the Ag vibrational (rotational) Raman mode in the Cmca phase might be the driving force to initiate the transition.

Testing the limits of sensitivity in a solid-state structural investigation by combined X-ray powder diffraction, solid-state NMR, and molecular modelling.

PubMed

Filip, Xenia; Borodi, Gheorghe; Filip, Claudiu

2011-10-28

A solid state structural investigation of ethoxzolamide is performed on microcrystalline powder by using a multi-technique approach that combines X-ray powder diffraction (XRPD) data analysis based on direct space methods with information from (13)C((15)N) solid-state Nuclear Magnetic Resonance (SS-NMR) and molecular modeling. Quantum chemical computations of the crystal were employed for geometry optimization and chemical shift calculations based on the Gauge Including Projector Augmented-Wave (GIPAW) method, whereas a systematic search in the conformational space was performed on the isolated molecule using a molecular mechanics (MM) approach. The applied methodology proved useful for: (i) removing ambiguities in the XRPD crystal structure determination process and further refining the derived structure solutions, and (ii) getting important insights into the relationship between the complex network of non-covalent interactions and the induced supra-molecular architectures/crystal packing patterns. It was found that ethoxzolamide provides an ideal case study for testing the accuracy with which this methodology allows to distinguish between various structural features emerging from the analysis of the powder diffraction data. This journal is © the Owner Societies 2011

Polarized atomic orbitals for self-consistent field electronic structure calculations

NASA Astrophysics Data System (ADS)

Lee, Michael S.; Head-Gordon, Martin

1997-12-01

We present a new self-consistent field approach which, given a large "secondary" basis set of atomic orbitals, variationally optimizes molecular orbitals in terms of a small "primary" basis set of distorted atomic orbitals, which are simultaneously optimized. If the primary basis is taken as a minimal basis, the resulting functions are termed polarized atomic orbitals (PAO's) because they are valence (or core) atomic orbitals which have distorted or polarized in an optimal way for their molecular environment. The PAO's derive their flexibility from the fact that they are formed from atom-centered linear-combinations of the larger set of secondary atomic orbitals. The variational conditions satisfied by PAO's are defined, and an iterative method for performing a PAO-SCF calculation is introduced. We compare the PAO-SCF approach against full SCF calculations for the energies, dipoles, and molecular geometries of various molecules. The PAO's are potentially useful for studying large systems that are currently intractable with larger than minimal basis sets, as well as offering potential interpretative benefits relative to calculations in extended basis sets.

The new 3-(tert-butyl)-1-(2-nitrophenyl)-1H-pyrazol-5-amine: Experimental and computational studies

NASA Astrophysics Data System (ADS)

Cuenú, Fernando; Muñoz-Patiño, Natalia; Torres, John Eduard; Abonia, Rodrigo; Toscano, Rubén A.; Cobo, J.

2017-11-01

The molecular and supramolecular structure of the title compound, 3-(tertbutyl)-1-(2-nitrophenyl)-1H-pyrazol-5-amine (2NPz) from the single crystal X-ray diffraction (SC-XRD) and spectroscopic data analysis is reported. The computational analysis of the structure, geometry optimization, vibrational frequencies, nuclear magnetic resonance and UV-Vis is also described and compared with experimental data. Satisfactory theoretical aspects were made for the molecule using density functional theory (DFT), with B3LYP and B3PW91 functionals, and Hartree-Fock (HF), with 6-311++G(d,p) basis set, using GAUSSIAN 09 program package without any constraint on the geometry. With VEDA 4 software, vibrational frequencies were assigned in terms of the potential energy distribution while, with the GaussSum software, the percentage contribution of the frontier orbitals at each transition of the electronic absorption spectrum was established. The obtained results indicated that optimized geometry could well reflect the molecular structural parameters from SC-XRD. Theoretical data obtained for the vibrational analysis and NMR spectra are consistent with experimental data.

Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach

NASA Astrophysics Data System (ADS)

Neves, Marco A. C.; Simões, Sérgio; Sá e Melo, M. Luisa

2010-12-01

CXCR4 is a G-protein coupled receptor for CXCL12 that plays an important role in human immunodeficiency virus infection, cancer growth and metastasization, immune cell trafficking and WHIM syndrome. In the absence of an X-ray crystal structure, theoretical modeling of the CXCR4 receptor remains an important tool for structure-function analysis and to guide the discovery of new antagonists with potential clinical use. In this study, the combination of experimental data and molecular modeling approaches allowed the development of optimized ligand-receptor models useful for elucidation of the molecular determinants of small molecule binding and functional antagonism. The ligand-guided homology modeling approach used in this study explicitly re-shaped the CXCR4 binding pocket in order to improve discrimination between known CXCR4 antagonists and random decoys. Refinement based on multiple test-sets with small compounds from single chemotypes provided the best early enrichment performance. These results provide an important tool for structure-based drug design and virtual ligand screening of new CXCR4 antagonists.

Magnetic behavior in Cr{sub 2}@Ge{sub n} (1≤n≤12) clusters: A density functional investigation

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

Dhaka, Kapil, E-mail: kapil.dhaka@pilani.bits-pilani.ac.in; Trivedi, Ravi, E-mail: kapil.dhaka@pilani.bits-pilani.ac.in; Bandyopadhyay, Debashis, E-mail: kapil.dhaka@pilani.bits-pilani.ac.in

2014-04-24

With a goal to produce magnetic moment in Cr{sub 2} Doped Ge{sub n} clusters which will be useful for practical applications, we have considered the structure and magnetic properties of Pure Germanium clusters and substitutionally doped it with Cr dimer to produce Cr{sub 2}@Ge{sub n} clusters. As the first step of calculation, geometrical optimizations of the nanoclusters have been done. These optimized geometries have been used in calculate the average binding energy per atom (BE), HOMO-LUMO gap and hence the relative stability of the clusters. These parameters have been demonstrated as structural and electronic properties of the clusters. Gap betweenmore » highest occupied molecular orbital and lowest unoccupied molecular orbital indicate cluster to be a potential motif for generating magnetic cluster assembled materials. Based on these values a comparative study on different sized clusters has been done in order to understand the origin of structures, electronic and magnetic properties of Cr{sub 2}@Ge{sub n} nanoclusters.« less

Polymerization and Structure of Bio-Based Plastics: A Computer Simulation

NASA Astrophysics Data System (ADS)

Khot, Shrikant N.; Wool, Richard P.

2001-03-01

We recently examined several hundred chemical pathways to convert chemically functionalized plant oil triglycerides, monoglycerides and reactive diluents into high performance plastics with a broad range of properties (US Patent No. 6,121,398). The resulting polymers had linear, branched, light- and highly-crosslinked chain architectures and could be used as pressure sensitive adhesives, elastomers and high performance rigid thermoset composite resins. To optimize the molecular design and minimize the number of chemical trials in this system with excess degrees of freedom, we developed a computer simulation of the free radical polymerization process. The triglyceride structure, degree of chemical substitution, mole fractions, fatty acid distribution function, and reaction kinetic parameters were used as initial inputs on a 3d lattice simulation. The evolution of the network fractal structure was computed and used to measure crosslink density, dangling ends, degree of reaction and defects in the lattice. The molecular connectivity was used to determine strength via a vector percolation model of fracture. The simulation permitted the optimal design of new bio-based materials with respect to monomer selection, cure reaction conditions and desired properties. Supported by the National Science Foundation

Preparation and Characterization of Organic-Inorganic Hybrid Macrocyclic Compounds: Cyclic Ladder-like Polyphenylsilsesquioxanes.

PubMed

Zhang, Wenchao; Wang, Xiaoxia; Wu, Yiwei; Qi, Zhi; Yang, Rongjie

2018-04-02

Organic-inorganic hybrid macrocyclic compounds, cyclic polyphenylsilsesquioxanes (cyc-PSQs), have been synthesized through hydrolysis and condensation reactions of phenyltrichlorosilane. Structural characterization has revealed that cyc-PSQs consist of a closed-ring double-chain siloxane inorganic backbone bearing organic phenyl groups. The cyc-PSQ molecules have been simulated and structurally optimized using the Forcite tool as implemented in Materials Studio. Structurally optimized cyc-PSQs are highly symmetrical and regular with high stereoregularity, consistent with the dimensions of their experimentally derived structures. Thermogravimetric analysis showed that these macrocyclic compounds have excellent thermal stability. In addition to these perfectly structured compounds, macrocyclic compounds with the same ring ladder structure but bearing an additional Si-OH group, cyc-PSQs-OH, have also been synthesized. A possible mechanism for the formation of the closed-ring molecular structures of cyc-PSQs and cyc-PSQs-OH is proposed.

Spontaneous polarization and dielectric relaxation dynamics of ferroelectric liquid crystals derived from 2(S)-[2(S)-ethylhexyolxy] propionic acid and its (S, R)-diastereomer

NASA Astrophysics Data System (ADS)

Huang, Lei-Ching; Fu, Chao-Ming

2015-09-01

The spontaneous polarization and molecular dynamics of four ferroelectric liquid crystals (FLCs) with two different kinds of core rings and two types of diastereomeric structures were investigated in this study. The FLCs with a biphenyl ring core structure showed higher spontaneous polarization than the FLCs with a naphthalene ring core structure. The complex dielectric spectra exhibited the Goldstone mode in the ferroelectric (SmC*) phase for all FLCs. The complex dielectric spectra of the four FLCs can be optimally fitted by the Debye model and the Cole-Cole model. Moreover, the Goldstone mode was enhanced under low DC bias fields for the FLCs with the (S, R)- diastereomeric structure, whereas the mode was suppressed for the FLCs with the (S, S)- diastereomeric structure. A microscopic molecular dynamic model is proposed to describe the underlying mechanism of the particular enhancement of the Goldstone mode. The experimental results of dielectric spectra and spontaneous polarization are explained in the discussion of the mesomorphic properties related to the FLC molecular structure.

An implicit divalent counterion force field for RNA molecular dynamics

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

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

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

Thermodynamic Studies for Drug Design and Screening

PubMed Central

Garbett, Nichola C.; Chaires, Jonathan B.

2012-01-01

Introduction A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically-driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development towards an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. PMID:22458502

Mono and binuclear ruthenium(II) complexes containing 5-chlorothiophene-2-carboxylic acid ligands: Spectroscopic analysis and computational studies

NASA Astrophysics Data System (ADS)

Swarnalatha, Kalaiyar; Kamalesu, Subramaniam; Subramanian, Ramasamy

2016-11-01

New Ruthenium complexes I, II and III were synthesized using 5-chlorothiophene-2-carboxylic acid (5TPC), as ligand and the complexes were characterized by elemental analysis, FT-IR, 1H, 13C NMR, and mass spectroscopic techniques. Photophysical and electrochemical studies were carried out and the structures of the synthesized complex were optimized using density functional theory (DFT). The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) energies and Mulliken atomic charges of the molecules are determined at the B3LYP method and standard 6-311++G (d,p) basis set starting from optimized geometry. They possess excellent stabilities and their thermal decomposition temperatures are 185 °C, 180 °C and 200 °C respectively, indicating that the metal complexes are suitable for the fabrication processes of optoelectronic devices.

Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation

NASA Astrophysics Data System (ADS)

Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

2012-12-01

We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation.

PubMed

Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

2012-12-07

We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

Structure-activity relationship of the ionic cocrystal: 5-amino-2-naphthalene sulfonate·ammonium ions for pharmaceutical applications

NASA Astrophysics Data System (ADS)

Sangeetha, M.; Mathammal, R.

2018-02-01

The ionic cocrystals of 5-amino-2-naphthalene sulfonate · ammonium ions (ANSA-ṡNH4+) were grown under slow evaporation method and examined in detail for pharmaceutical applications. The crystal structure and intermolecular interactions were studied from the single X-ray diffraction analysis and the Hirshfeld surfaces. The 2D fingerprint plots displayed the inter-contacts possible in the ionic crystal. Computational DFT method was established to determine the structural, physical and chemical properties. The molecular geometries obtained from the X-ray studies were compared with the optimized geometrical parameters calculated using DFT/6-31 + G(d,p) method. The band gap energy calculated from the UV-Visible spectral analysis and the HOMO-LUMO energy gap are compared. The theoretical UV-Visible calculations helped in determining the type of electronic transition taking place in the title molecule. The maximum absorption bands and transitions involved in the molecule represented the drug reaction possible. Non-linear optical properties were characterized from SHG efficiency measurements experimentally and the NLO parameters are also calculated from the optimized structure. The reactive sites within the molecule are detailed from the MEP surface maps. The molecular docking studies evident the structure-activity of the ionic cocrystal for anti-cancer drug property.

De novo design of molecular architectures by evolutionary assembly of drug-derived building blocks.

PubMed

Schneider, G; Lee, M L; Stahl, M; Schneider, P

2000-07-01

An evolutionary algorithm was developed for fragment-based de novo design of molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at generating a novel molecular structure mimicking a template structure. A set of approximately 25,000 fragment structures serves as the building block supply, which were obtained by a straightforward fragmentation procedure applied to 36,000 known drugs. Eleven reaction schemes were implemented for both fragmentation and building block assembly. This combination of drug-derived building blocks and a restricted set of reaction schemes proved to be a key for the automatic development of novel, synthetically tractable structures. In a cyclic optimization process, molecular architectures were generated from a parent structure by virtual synthesis, and the best structure of a generation was selected as the parent for the subsequent TOPAS cycle. Similarity measures were used to define 'fitness', based on 2D-structural similarity or topological pharmacophore distance between the template molecule and the variants. The concept of varying library 'diversity' during a design process was consequently implemented by using adaptive variant distributions. The efficiency of the design algorithm was demonstrated for the de novo construction of potential thrombin inhibitors mimicking peptide and non-peptide template structures.

Infrared spectrum, structural and optical properties and molecular docking study of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde.

PubMed

Mary, Y Sheena; Panicker, C Yohannan; Sapnakumari, M; Narayana, B; Sarojini, B K; Al-Saadi, Abdulaziz A; Van Alsenoy, C; War, Javeed Ahmad; Fun, H K

2015-03-05

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde have been investigated experimentally and theoretically. The title compound was optimized using at HF and DFT levels of calculations. The B3LYP/6-311++G(d,p) (5D,7F) results and in agreement with experimental infrared bands. The normal modes are assigned using potential energy distribution. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using natural bonding orbital analysis. The frontier molecular orbital analysis is used to determine the charge transfer within the molecule. From molecular electrostatic potential map, it is evident that the negative electrostatic potential regions are mainly localized over the carbonyl group and mono substituted phenyl ring and are possible sites for electrophilic attack and, positive regions are localized around all para substituted phenyl and pyrazole ring, indicating possible sites for nucleophilic attack. First hyperpolarizability is calculated in order to find its role in nonlinear optics. The geometrical parameters are in agreement with experimental data. From the molecular docking studies, it is evident that the fluorine atom attached to phenyl ring and the carbonyl group attached to pyrazole ring are crucial for binding and the results draw us to the conclusion that the compound might exhibit phosphodiesterase inhibitory activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Postprocessing of docked protein-ligand complexes using implicit solvation models.

PubMed

Lindström, Anton; Edvinsson, Lotta; Johansson, Andreas; Andersson, C David; Andersson, Ida E; Raubacher, Florian; Linusson, Anna

2011-02-28

Molecular docking plays an important role in drug discovery as a tool for the structure-based design of small organic ligands for macromolecules. Possible applications of docking are identification of the bioactive conformation of a protein-ligand complex and the ranking of different ligands with respect to their strength of binding to a particular target. We have investigated the effect of implicit water on the postprocessing of binding poses generated by molecular docking using MM-PB/GB-SA (molecular mechanics Poisson-Boltzmann and generalized Born surface area) methodology. The investigation was divided into three parts: geometry optimization, pose selection, and estimation of the relative binding energies of docked protein-ligand complexes. Appropriate geometry optimization afforded more accurate binding poses for 20% of the complexes investigated. The time required for this step was greatly reduced by minimizing the energy of the binding site using GB solvation models rather than minimizing the entire complex using the PB model. By optimizing the geometries of docking poses using the GB(HCT+SA) model then calculating their free energies of binding using the PB implicit solvent model, binding poses similar to those observed in crystal structures were obtained. Rescoring of these poses according to their calculated binding energies resulted in improved correlations with experimental binding data. These correlations could be further improved by applying the postprocessing to several of the most highly ranked poses rather than focusing exclusively on the top-scored pose. The postprocessing protocol was successfully applied to the analysis of a set of Factor Xa inhibitors and a set of glycopeptide ligands for the class II major histocompatibility complex (MHC) A(q) protein. These results indicate that the protocol for the postprocessing of docked protein-ligand complexes developed in this paper may be generally useful for structure-based design in drug discovery.

Spectroscopic, quantum chemical calculation and molecular docking of dipfluzine

NASA Astrophysics Data System (ADS)

Srivastava, Karnica; Srivastava, Anubha; Tandon, Poonam; Sinha, Kirti; Wang, Jing

2016-12-01

Molecular structure and vibrational analysis of dipfluzine (C27H29FN2O) were presented using FT-IR and FT-Raman spectroscopy and quantum chemical calculations. The theoretical ground state geometry and electronic structure of dipfluzine are optimized by the DFT/B3LYP/6-311++G (d,p) method and compared with those of the crystal data. The 1D potential energy scan was performed by varying the dihedral angle using B3LYP functional at 6-31G(d,p) level of theory and thus the most stable conformer of the compound were determined. Molecular electrostatic potential surface (MEPS), frontier orbital analysis and electronic reactivity descriptor were used to predict the chemical reactivity of molecule. Energies of intra- and inter-molecular hydrogen bonds in molecule and their electronic aspects were investigated by natural bond orbital (NBO). To find out the anti-apoptotic activity of the title compound molecular docking studies have been performed against protein Fas.

Molecular structure and vibrational spectra of Bis(melaminium) terephthalate dihydrate: A DFT computational study

NASA Astrophysics Data System (ADS)

Tanak, Hasan; Marchewka, Mariusz K.; Drozd, Marek

2013-03-01

The experimental and theoretical vibrational spectra of Bis(melaminium) terephthalate dihydrate were studied. The Fourier transform infrared (FT-IR) spectra of the Bis(melaminium) terephthalate dihydrate and its deuterated analogue were recorded in the solid phase. The molecular geometry and vibrational frequencies of Bis(melaminium) terephthalate dihydrate in the ground state have been calculated by using the density functional method (B3LYP) with 6-31++G(d,p) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction. The molecule contains the weak hydrogen bonds of Nsbnd H⋯O, Nsbnd H⋯N and Osbnd H⋯O types, and those bonds are calculated with DFT method. In addition, molecular electrostatic potential, frontier molecular orbitals and natural bond orbital analysis of the title compound were investigated by theoretical calculations. The lack of the second harmonic generation (SHG) confirms the presence of macroscopic center of inversion.

Molecular structure and vibrational spectra of Bis(melaminium) terephthalate dihydrate: a DFT computational study.

PubMed

Tanak, Hasan; Marchewka, Mariusz K; Drozd, Marek

2013-03-15

The experimental and theoretical vibrational spectra of Bis(melaminium) terephthalate dihydrate were studied. The Fourier transform infrared (FT-IR) spectra of the Bis(melaminium) terephthalate dihydrate and its deuterated analogue were recorded in the solid phase. The molecular geometry and vibrational frequencies of Bis(melaminium) terephthalate dihydrate in the ground state have been calculated by using the density functional method (B3LYP) with 6-31++G(d,p) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction. The molecule contains the weak hydrogen bonds of N-H···O, N-H···N and O-H···O types, and those bonds are calculated with DFT method. In addition, molecular electrostatic potential, frontier molecular orbitals and natural bond orbital analysis of the title compound were investigated by theoretical calculations. The lack of the second harmonic generation (SHG) confirms the presence of macroscopic center of inversion. Copyright © 2012 Elsevier B.V. All rights reserved.

Library design practices for success in lead generation with small molecule libraries.

PubMed

Goodnow, R A; Guba, W; Haap, W

2003-11-01

The generation of novel structures amenable to rapid and efficient lead optimization comprises an emerging strategy for success in modern drug discovery. Small molecule libraries of sufficient size and diversity to increase the chances of discovery of novel structures make the high throughput synthesis approach the method of choice for lead generation. Despite an industry trend for smaller, more focused libraries, the need to generate novel lead structures makes larger libraries a necessary strategy. For libraries of a several thousand or more members, solid phase synthesis approaches are the most suitable. While the technology and chemistry necessary for small molecule library synthesis continue to advance, success in lead generation requires rigorous consideration in the library design process to ensure the synthesis of molecules possessing the proper characteristics for subsequent lead optimization. Without proper selection of library templates and building blocks, solid phase synthesis methods often generate molecules which are too heavy, too lipophilic and too complex to be useful for lead optimization. The appropriate filtering of virtual library designs with multiple computational tools allows the generation of information-rich libraries within a drug-like molecular property space. An understanding of the hit-to-lead process provides a practical guide to molecular design characteristics. Examples of leads generated from library approaches also provide a benchmarking of successes as well as aspects for continued development of library design practices.

Protein engineering and the use of molecular modeling and simulation: the case of heterodimeric Fc engineering.

PubMed

Spreter Von Kreudenstein, Thomas; Lario, Paula I; Dixit, Surjit B

2014-01-01

Computational and structure guided methods can make significant contributions to the development of solutions for difficult protein engineering problems, including the optimization of next generation of engineered antibodies. In this paper, we describe a contemporary industrial antibody engineering program, based on hypothesis-driven in silico protein optimization method. The foundational concepts and methods of computational protein engineering are discussed, and an example of a computational modeling and structure-guided protein engineering workflow is provided for the design of best-in-class heterodimeric Fc with high purity and favorable biophysical properties. We present the engineering rationale as well as structural and functional characterization data on these engineered designs. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis, structural characterization and comparison of experimental and theoretical results by DFT level of molecular structure of 4-(4-methoxyphenethyl)-3,5-dimethyl-4H-1,2,4-triazole.

PubMed

Düğdü, Esra; Ünver, Yasemin; Ünlüer, Dilek; Tanak, Hasan; Sancak, Kemal; Köysal, Yavuz; Işık, Şamil

2013-05-01

4-(4-Methoxyphenethyl)-3,5-dimethyl-4H-1,2,4-triazole (3) was synthesized from the reaction of ethyl N'-acetylacetohydrazonate (1) with 2-(4-methoxyphenyl)ethanamine (2). The structure of the title compound 3 has been inferred through IR, (1)H/(13)C NMR, mass spectrometry, elemental analyses and combination of X-ray crystallography and theoretical methods. In addition to the molecular geometry from X-ray determination, the molecular geometry and vibrational frequencies of the title compound 3 in the ground state, were calculated using the density functional method (B3LYP) with the 6-31G(d) basis set. The calculated results show that the optimized geometry can well reproduce the crystal structure and the theoretical vibrational frequencies show good agreement with experimental values. The nonlinear optical properties are also addressed theoretically. The predicted nonlinear optical properties of 3 are greater than ones of urea. In addition, DFT calculations of molecular electrostatic potentials and frontier molecular orbitals of the title compound were carried out at the B3LYP/6-31G(d) level of theory. Copyright © 2012. Published by Elsevier B.V.

Theoretical study on the vibrational spectra of methoxy- and formyl-dihydroxy- trans-stilbenes and their hydrolytic equilibria

NASA Astrophysics Data System (ADS)

Molnár, Viktor; Billes, Ferenc; Tyihák, Ernő; Mikosch, Hans

2008-02-01

Compounds formed by exchanging one of the resveratrol hydroxy groups to methoxy or formyl groups are biologically important. Quantum chemical DFT calculations were applied for the simulation of some of their properties. Their optimized structures and charge distributions were computed. Based on the calculated vibrational force constants and optimized molecular structure infrared and Raman spectra were calculated. The characteristics of the vibrational modes were determined by normal coordinate analysis. Applying the calculated thermodynamic functions also for resveratrol, methanol, formaldehyde and water, thermodynamic equilibria were calculated for the equilibria between resveratrol and its methyl and formyl substituted derivatives, respectively.

Molecular modeling of calmodulin: a comparison with crystallographic data

NASA Technical Reports Server (NTRS)

McDonald, J. J.; Rein, R.

1989-01-01

Two methods of side-chain placement on a modeled protein have been examined. Two molecular models of calmodulin were constructed that differ in the treatment of side chains prior to optimization of the molecule. A virtual bond analysis program developed by Purisima and Scheraga was used to determine the backbone conformation based on 2.2 angstroms resolution C alpha coordinates for the molecules. In the first model, side chains were initially constructed in an extended conformation. In the second model, a conformational grid search technique was employed. Calcium ions were treated explicitly during energy optimization using CHARMM. The models are compared to a recently published refined crystal structure of calmodulin. The results indicate that the initial choices for side-chains, but also significant effects on the main-chain conformation and supersecondary structure. The conformational differences are discussed. Analysis of these and other methods makes possible the formulation of a methodology for more appropriate side-chain placement in modeled proteins.

Molecular Level Design Principle behind Optimal Sizes of Photosynthetic LH2 Complex: Taming Disorder through Cooperation of Hydrogen Bonding and Quantum Delocalization.

PubMed

Jang, Seogjoo; Rivera, Eva; Montemayor, Daniel

2015-03-19

The light harvesting 2 (LH2) antenna complex from purple photosynthetic bacteria is an efficient natural excitation energy carrier with well-known symmetric structure, but the molecular level design principle governing its structure-function relationship is unknown. Our all-atomistic simulations of nonnatural analogues of LH2 as well as those of a natural LH2 suggest that nonnatural sizes of LH2-like complexes could be built. However, stable and consistent hydrogen bonding (HB) between bacteriochlorophyll and the protein is shown to be possible only near naturally occurring sizes, leading to significantly smaller disorder than for nonnatural ones. Extensive quantum calculations of intercomplex exciton transfer dynamics, sampled for a large set of disorder, reveal that taming the negative effect of disorder through a reliable HB as well as quantum delocalization of the exciton is a critical mechanism that makes LH2 highly functional, which also explains why the natural sizes of LH2 are indeed optimal.

Molecular beam epitaxy growth of high electron mobility InAs/AlSb deep quantum well structure

NASA Astrophysics Data System (ADS)

Wang, Juan; Wang, Guo-Wei; Xu, Ying-Qiang; Xing, Jun-Liang; Xiang, Wei; Tang, Bao; Zhu, Yan; Ren, Zheng-Wei; He, Zhen-Hong; Niu, Zhi-Chuan

2013-07-01

InAs/AlSb deep quantum well (QW) structures with high electron mobility were grown by molecular beam epitaxy (MBE) on semi-insulating GaAs substrates. AlSb and Al0.75Ga0.25Sb buffer layers were grown to accommodate the lattice mismatch (7%) between the InAs/AlSb QW active region and GaAs substrate. Transmission electron microscopy shows abrupt interface and atomic force microscopy measurements display smooth surface morphology. Growth conditions of AlSb and Al0.75Ga0.25Sb buffer were optimized. Al0.75Ga0.25Sb is better than AlSb as a buffer layer as indicated. The sample with optimal Al0.75Ga0.25Sb buffer layer shows a smooth surface morphology with root-mean-square roughness of 6.67 Å. The electron mobility has reached as high as 27 000 cm2/Vs with a sheet density of 4.54 × 1011/cm2 at room temperature.

Enhancing the Thermoelectric Figure of Merit by Low-Dimensional Electrical Transport in Phonon-Glass Crystals.

PubMed

Mi, Xue-Ya; Yu, Xiaoxiang; Yao, Kai-Lun; Huang, Xiaoming; Yang, Nuo; Lü, Jing-Tao

2015-08-12

Low-dimensional electronic and glassy phononic transport are two important ingredients of highly efficient thermoelectric materials, from which two branches of thermoelectric research have emerged. One focuses on controlling electronic transport in the low dimension, while the other focuses on multiscale phonon engineering in the bulk. Recent work has benefited much from combining these two approaches, e.g., phonon engineering in low-dimensional materials. Here we propose to employ the low-dimensional electronic structure in bulk phonon-glass crystals as an alternative way to increase the thermoelectric efficiency. Through first-principles electronic structure calculations and classical molecular dynamics simulations, we show that the π-π-stacking bis(dithienothiophene) molecular crystal is a natural candidate for such an approach. This is determined by the nature of its chemical bonding. Without any optimization of the material parameters, we obtained a maximum room-temperature figure of merit, ZT, of 1.48 at optimal doping, thus validating our idea.

DFT calculation and vibrational spectroscopic studies of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine.

PubMed

Premkumar, S; Jawahar, A; Mathavan, T; Kumara Dhas, M; Sathe, V G; Milton Franklin Benial, A

2014-08-14

The molecular structure of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine (BABP) was optimized by the DFT/B3LYP method with 6-311G (d,p), 6-311++G (d,p) and cc-pVTZ basis sets using the Gaussian 09 program. The most stable optimized structure of the molecule was predicted by the DFT/B3LYP method with cc-pVTZ basis set. The vibrational frequencies, Mulliken atomic charge distribution, frontier molecular orbitals and thermodynamical parameters were calculated. These calculations were done at the ground state energy level of BABP without applying any constraint on the potential energy surface. The vibrational spectra were experimentally recorded using Fourier Transform-Infrared (FT-IR) and micro-Raman spectrometer. The computed vibrational frequencies were scaled by scale factors to yield a good agreement with observed experimental vibrational frequencies. The complete theoretically calculated and experimentally observed vibrational frequencies were assigned on the basis of Potential Energy Distribution (PED) calculation using the VEDA 4.0 program. The vibrational modes assignments were performed by using the animation option of GaussView 05 graphical interface for Gaussian program. The Mulliken atomic charge distribution was calculated for BABP molecule. The molecular reactivity and stability of BABP were also studied by frontier molecular orbitals (FMOs) analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Density functional theory analysis and molecular docking evaluation of 1-(2, 5-dichloro-4-sulfophenyl)-3-methyl-5-pyrazolone as COX2 inhibitor against inflammatory diseases

NASA Astrophysics Data System (ADS)

Kavitha, T.; Velraj, G.

2017-08-01

The molecular structure of 1-(2, 5-Dichloro-4-Sulfophenyl)-3-Methyl-5-Pyrazolone (DSMP) was optimized using DFT/B3LYP/6-31++G(d,p) level and its corresponding experimental as well as theoretical FT-IR, FT-Raman vibrational frequencies and UV-Vis spectral analysis were carried out. The vibrational assignments and total energy distributions of each vibration were presented with the aid of Veda 4xx software. The molecular electrostatic potential, HOMO-LUMO energies, global and local reactivity descriptors and natural bond orbitals were analyzed in order to find the most possible reactive sites of the molecule and it was found that DSMP molecule possess enhanced nucleophilic activity. One of the common known COX2 inhibitor, celecoxib (CXB) was also found to exhibit similar reactivity properties and hence DSMP was also expected to inhibit COX enzymes. In order to detect the COX inhibition nature of DSMP, molecular docking analysis was carried out with the help of Autodock software. For that, the optimized structure was in turn used for docking DSMP with COX enzymes. The binding energy scores and inhibitory constant values reveal that the DSMP molecule possess good binding affinity and low inhibition constant towards COX2 enzyme and hence it can be used as an anti-inflammatory drug after carrying out necessary biological tests.

Toward the identification of molecular cogs.

PubMed

Dziubiński, Maciej; Lesyng, Bogdan

2016-04-05

Computer simulations of molecular systems allow determination of microscopic interactions between individual atoms or groups of atoms, as well as studies of intramolecular motions. Nevertheless, description of structural transformations at the mezoscopic level and identification of causal relations associated with these transformations is very difficult. Structural and functional properties are related to free energy changes. Therefore, to better understand structural and functional properties of molecular systems, it is required to deepen our knowledge of free energy contributions arising from molecular subsystems in the course of structural transformations. The method presented in this work quantifies the energetic contribution of each pair of atoms to the total free energy change along a given collective variable. Next, with the help of a genetic clustering algorithm, the method proposes a division of the system into two groups of atoms referred to as molecular cogs. Atoms which cooperate to push the system forward along a collective variable are referred to as forward cogs, and those which work in the opposite direction as reverse cogs. The procedure was tested on several small molecules for which the genetic clustering algorithm successfully found optimal partitionings into molecular cogs. The primary result of the method is a plot depicting the energetic contributions of the identified molecular cogs to the total Potential of Mean Force (PMF) change. Case-studies presented in this work should help better understand the implications of our approach, and were intended to pave the way to a future, publicly available implementation. © 2015 Wiley Periodicals, Inc.

Theoretical study on the antitumor properties of Ru(II) complexes containing 2-pyridyl, 2-pyridine-4-carboxylic acid ligands

NASA Astrophysics Data System (ADS)

Erkan kariper, Sultan; Sayin, Koray; Karakaş, Duran

2017-12-01

[Ru(bipy)2(CppH)]2+(1), [Ru(bipy)2(Cpp-NH-Hex-COOH)]2+(2), [Ru(dppz)2(CppH)]2+(3) and [Ru(dppz)2(Cpp-NH-Hex-COOH)]2+(4) were calculated by Hartree-Fock (HF), Density Functional Theory (DFT) hybrid B3LYP and Moller-Plesset Perturbation (MPn n = 2,3) theory method and CEP-4G, CEP-31G, CEP-121G, LANL2DZ, LANL2MB, SDD basic sets and a mixed basic set with the keyword GEN in gas phase and water. Structure parameters obtained from optimized structures were compared with experimental parameters. M062X/(6-31G(d))(CEP-4G) level was taken into account for the most appropriate calculation level. IR, UV-VIS and NMR spectrums were examined for structural characterization. The optimal structure was identified via structure parameters, IR, UV-VIS and NMR spectrums. For the most compatible structure, the highest molecular orbital energy (EHOMO) which one of the most effective chemical determiners on the antitumor activity of the complexes, the lowest molecular orbital energy (ELUMO), LUMO-HOMO energy gap, hardness (η), softness (σ), electronegativity (χ), chemical potential (μ), electrophilicity index (ω), molar volume (V), dipole moment (DM), total negative charge (TNC), enthalpy (H), entropy (S) and total energy (E) were calculated. The causes of anticancer activity of the complexes have been studied.

Lead optimization using matched molecular pairs: inclusion of contextual information for enhanced prediction of HERG inhibition, solubility, and lipophilicity.

PubMed

Papadatos, George; Alkarouri, Muhammad; Gillet, Valerie J; Willett, Peter; Kadirkamanathan, Visakan; Luscombe, Christopher N; Bravi, Gianpaolo; Richmond, Nicola J; Pickett, Stephen D; Hussain, Jameed; Pritchard, John M; Cooper, Anthony W J; Macdonald, Simon J F

2010-10-25

Previous studies of the analysis of molecular matched pairs (MMPs) have often assumed that the effect of a substructural transformation on a molecular property is independent of the context (i.e., the local structural environment in which that transformation occurs). Experiments with large sets of hERG, solubility, and lipophilicity data demonstrate that the inclusion of contextual information can enhance the predictive power of MMP analyses, with significant trends (both positive and negative) being identified that are not apparent when using conventional, context-independent approaches.

Computational studies of novel chymase inhibitors against cardiovascular and allergic diseases: mechanism and inhibition.

PubMed

Arooj, Mahreen; Thangapandian, Sundarapandian; John, Shalini; Hwang, Swan; Park, Jong K; Lee, Keun W

2012-12-01

To provide a new idea for drug design, a computational investigation is performed on chymase and its novel 1,4-diazepane-2,5-diones inhibitors that explores the crucial molecular features contributing to binding specificity. Molecular docking studies of inhibitors within the active site of chymase were carried out to rationalize the inhibitory properties of these compounds and understand their inhibition mechanism. The density functional theory method was used to optimize molecular structures with the subsequent analysis of highest occupied molecular orbital, lowest unoccupied molecular orbital, and molecular electrostatic potential maps, which revealed that negative potentials near 1,4-diazepane-2,5-diones ring are essential for effective binding of inhibitors at active site of enzyme. The Bayesian model with receiver operating curve statistic of 0.82 also identified arylsulfonyl and aminocarbonyl as the molecular features favoring and not favoring inhibition of chymase, respectively. Moreover, genetic function approximation was applied to construct 3D quantitative structure-activity relationships models. Two models (genetic function approximation model 1 r(2) = 0.812 and genetic function approximation model 2 r(2) = 0.783) performed better in terms of correlation coefficients and cross-validation analysis. In general, this study is used as example to illustrate how combinational use of 2D/3D quantitative structure-activity relationships modeling techniques, molecular docking, frontier molecular orbital density fields (highest occupied molecular orbital and lowest unoccupied molecular orbital), and molecular electrostatic potential analysis may be useful to gain an insight into the binding mechanism between enzyme and its inhibitors. © 2012 John Wiley & Sons A/S.

Predicting activation energy of thermolysis of polynitro arenes through molecular structure.

PubMed

Keshavarz, Mohammad Hossein; Pouretedal, Hamid Reza; Shokrolahi, Arash; Zali, Abbas; Semnani, Abolfazl

2008-12-15

The paper presents a new method for activation energy or the Arrhenius parameter E(a) of the thermolysis in the condensed state for different polynitro arenes as an important class of energetic molecules. The methodology assumes that E(a) of a polynitro arene with general formula C(a)H(b)N(c)O(d) can be expressed as a function of optimized elemental composition as well as the contribution of specific molecular structural parameters. The new method can predict E(a) of the thermolysis under conditions of Soviet Manometric Method (SMM), which can be related to the other convenient methods. The new correlation has the root mean square (rms) and the average deviations of 13.79 and 11.94kJ/mol, respectively, for 20 polynitro arenes with different molecular structures. The proposed new method can also be used to predict E(a) of three polynitro arenes, i.e. 2,2',2'',4,4',4'',6,6',6''-nonanitro-1,1':3',1''-terphenyl (NONA), 3,3'-diamino-2,2',4,4',6,6'-hexanitro-1,1'-biphenyl-3,3'-diamine (DIPAM) and N,N-bis(2,4-dinitrophenyl)-2,4,6-trinitroaniline (NTFA), which have complex molecular structures.

Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

PubMed Central

2011-01-01

Background Molecular dynamics (MD) simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs) were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to conformational ensembles from other sources. PMID:21569575

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

PubMed Central

Chen, Alan A.; García, Angel E.

2013-01-01

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

Modeling the intermolecular interactions: molecular structure of N-3-hydroxyphenyl-4-methoxybenzamide.

PubMed

Karabulut, Sedat; Namli, Hilmi; Kurtaran, Raif; Yildirim, Leyla Tatar; Leszczynski, Jerzy

2014-03-01

The title compound, N-3-hydroxyphenyl-4-methoxybenzamide (3) was prepared by the acylation reaction of 3-aminophenol (1) and 4-metoxybenzoylchloride (2) in THF and characterized by ¹H NMR, ¹³C NMR and elemental analysis. Molecular structure of the crystal was determined by single crystal X-ray diffraction and DFT calculations. 3 crystallizes in monoclinic P2₁/c space group. The influence of intermolecular interactions (dimerization and crystal packing) on molecular geometry has been evaluated by calculations performed for three different models; monomer (3), dimer (4) and dimer with added unit cell contacts (5). Molecular structure of 3, 4 and 5 was optimized by applying B3LYP method with 6-31G+(d,p) basis set in gas phase and compared with X-ray crystallographic data including bond lengths, bond angles and selected dihedral angles. It has been concluded that although the crystal packing and dimerization have a minor effect on bond lengths and angles, however, these interactions are important for the dihedral angles and the rotational conformation of aromatic rings. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of neighborhood behavior in lead optimization and array design.

PubMed

Papadatos, George; Cooper, Anthony W J; Kadirkamanathan, Visakan; Macdonald, Simon J F; McLay, Iain M; Pickett, Stephen D; Pritchard, John M; Willett, Peter; Gillet, Valerie J

2009-02-01

Neighborhood behavior describes the extent to which small structural changes defined by a molecular descriptor are likely to lead to small property changes. This study evaluates two methods for the quantification of neighborhood behavior: the optimal diagonal method of Patterson et al. and the optimality criterion method of Horvath and Jeandenans. The methods are evaluated using twelve different types of fingerprint (both 2D and 3D) with screening data derived from several lead optimization projects at GlaxoSmithKline. The principal focus of the work is the design of chemical arrays during lead optimization, and the study hence considers not only biological activity but also important drug properties such as metabolic stability, permeability, and lipophilicity. Evidence is provided to suggest that the optimality criterion method may provide a better quantitative description of neighborhood behavior than the optimal diagonal method.

Performance of extended Lagrangian schemes for molecular dynamics simulations with classical polarizable force fields and density functional theory

NASA Astrophysics Data System (ADS)

Vitale, Valerio; Dziedzic, Jacek; Albaugh, Alex; Niklasson, Anders M. N.; Head-Gordon, Teresa; Skylaris, Chris-Kriton

2017-03-01

Iterative energy minimization with the aim of achieving self-consistency is a common feature of Born-Oppenheimer molecular dynamics (BOMD) and classical molecular dynamics with polarizable force fields. In the former, the electronic degrees of freedom are optimized, while the latter often involves an iterative determination of induced point dipoles. The computational effort of the self-consistency procedure can be reduced by re-using converged solutions from previous time steps. However, this must be done carefully, as not to break time-reversal symmetry, which negatively impacts energy conservation. Self-consistent schemes based on the extended Lagrangian formalism, where the initial guesses for the optimized quantities are treated as auxiliary degrees of freedom, constitute one elegant solution. We report on the performance of two integration schemes with the same underlying extended Lagrangian structure, which we both employ in two radically distinct regimes—in classical molecular dynamics simulations with the AMOEBA polarizable force field and in BOMD simulations with the Onetep linear-scaling density functional theory (LS-DFT) approach. Both integration schemes are found to offer significant improvements over the standard (unpropagated) molecular dynamics formulation in both the classical and LS-DFT regimes.

Performance of extended Lagrangian schemes for molecular dynamics simulations with classical polarizable force fields and density functional theory.

PubMed

Vitale, Valerio; Dziedzic, Jacek; Albaugh, Alex; Niklasson, Anders M N; Head-Gordon, Teresa; Skylaris, Chris-Kriton

2017-03-28

Iterative energy minimization with the aim of achieving self-consistency is a common feature of Born-Oppenheimer molecular dynamics (BOMD) and classical molecular dynamics with polarizable force fields. In the former, the electronic degrees of freedom are optimized, while the latter often involves an iterative determination of induced point dipoles. The computational effort of the self-consistency procedure can be reduced by re-using converged solutions from previous time steps. However, this must be done carefully, as not to break time-reversal symmetry, which negatively impacts energy conservation. Self-consistent schemes based on the extended Lagrangian formalism, where the initial guesses for the optimized quantities are treated as auxiliary degrees of freedom, constitute one elegant solution. We report on the performance of two integration schemes with the same underlying extended Lagrangian structure, which we both employ in two radically distinct regimes-in classical molecular dynamics simulations with the AMOEBA polarizable force field and in BOMD simulations with the Onetep linear-scaling density functional theory (LS-DFT) approach. Both integration schemes are found to offer significant improvements over the standard (unpropagated) molecular dynamics formulation in both the classical and LS-DFT regimes.

Performance of extended Lagrangian schemes for molecular dynamics simulations with classical polarizable force fields and density functional theory

DOE PAGES

Vitale, Valerio; Dziedzic, Jacek; Albaugh, Alex; ...

2017-03-28

Iterative energy minimization with the aim of achieving self-consistency is a common feature of Born-Oppenheimer molecular dynamics (BOMD) and classical molecular dynamics with polarizable force fields. In the former, the electronic degrees of freedom are optimized, while the latter often involves an iterative determination of induced point dipoles. The computational effort of the self-consistency procedure can be reduced by re-using converged solutions from previous time steps. However, this must be done carefully, as not to break time-reversal symmetry, which negatively impacts energy conservation. Self-consistent schemes based on the extended Lagrangian formalism, where the initial guesses for the optimized quantities aremore » treated as auxiliary degrees of freedom, constitute one elegant solution. We report on the performance of two integration schemes with the same underlying extended Lagrangian structure, which we both employ in two radically distinct regimes—in classical molecular dynamics simulations with the AMOEBA polarizable force field and in BOMD simulations with the Onetep linear-scaling density functional theory (LS-DFT) approach. Furthermore, both integration schemes are found to offer significant improvements over the standard (unpropagated) molecular dynamics formulation in both the classical and LS-DFT regimes.« less

Performance of extended Lagrangian schemes for molecular dynamics simulations with classical polarizable force fields and density functional theory

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

Vitale, Valerio; Dziedzic, Jacek; Albaugh, Alex

Iterative energy minimization with the aim of achieving self-consistency is a common feature of Born-Oppenheimer molecular dynamics (BOMD) and classical molecular dynamics with polarizable force fields. In the former, the electronic degrees of freedom are optimized, while the latter often involves an iterative determination of induced point dipoles. The computational effort of the self-consistency procedure can be reduced by re-using converged solutions from previous time steps. However, this must be done carefully, as not to break time-reversal symmetry, which negatively impacts energy conservation. Self-consistent schemes based on the extended Lagrangian formalism, where the initial guesses for the optimized quantities aremore » treated as auxiliary degrees of freedom, constitute one elegant solution. We report on the performance of two integration schemes with the same underlying extended Lagrangian structure, which we both employ in two radically distinct regimes—in classical molecular dynamics simulations with the AMOEBA polarizable force field and in BOMD simulations with the Onetep linear-scaling density functional theory (LS-DFT) approach. Furthermore, both integration schemes are found to offer significant improvements over the standard (unpropagated) molecular dynamics formulation in both the classical and LS-DFT regimes.« less

Protein-protein structure prediction by scoring molecular dynamics trajectories of putative poses.

PubMed

Sarti, Edoardo; Gladich, Ivan; Zamuner, Stefano; Correia, Bruno E; Laio, Alessandro

2016-09-01

The prediction of protein-protein interactions and their structural configuration remains a largely unsolved problem. Most of the algorithms aimed at finding the native conformation of a protein complex starting from the structure of its monomers are based on searching the structure corresponding to the global minimum of a suitable scoring function. However, protein complexes are often highly flexible, with mobile side chains and transient contacts due to thermal fluctuations. Flexibility can be neglected if one aims at finding quickly the approximate structure of the native complex, but may play a role in structure refinement, and in discriminating solutions characterized by similar scores. We here benchmark the capability of some state-of-the-art scoring functions (BACH-SixthSense, PIE/PISA and Rosetta) in discriminating finite-temperature ensembles of structures corresponding to the native state and to non-native configurations. We produce the ensembles by running thousands of molecular dynamics simulations in explicit solvent starting from poses generated by rigid docking and optimized in vacuum. We find that while Rosetta outperformed the other two scoring functions in scoring the structures in vacuum, BACH-SixthSense and PIE/PISA perform better in distinguishing near-native ensembles of structures generated by molecular dynamics in explicit solvent. Proteins 2016; 84:1312-1320. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Synthesis of surface molecular imprinted polymers based on carboxyl-modified silica nanoparticles with the selective detection of dibutyl phthalate from tap water samples

NASA Astrophysics Data System (ADS)

Xu, Wanzhen; Zhang, Xiaoming; Huang, Weihong; Luan, Yu; Yang, Yanfei; Zhu, Maiyong; Yang, Wenming

2017-12-01

In this work, the molecular imprinted polymers were synthesized with the low monomer concentrations for dibutyl phthalate (DBP). The polymers were prepared over carboxyl-modified silica nanoparticle, which used methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker agent and azoisobutyronitrile as the initiator in the process of preparation. Various measures were used to characterize the structure and morphology in order to get the optimal polymer. The characterization results show that the optimal polymer has suitable features for further adsorption process. And adsorption capacity experiments were evaluated to analyze its adsorption performance, through adsorption isotherms/kinetics, selectivity adsorption and desorption and regeneration experiments. These results showed that the molecular imprinted polymers had a short equilibrium time about 60 min and high stability with 88% after six cycles. Furthermore, the molecular imprinted polymers were successfully applied to remove dibutyl phthalate. The concentration range was 5.0-30.0 μmol L-1, and the limit of detection was 0.06 μmol L-1 in tap water samples.

Ab initio conformational analysis of N-formyl ?-alanine amide including electron correlation

NASA Astrophysics Data System (ADS)

Yu, Ching-Hsing; Norman, Mya A.; Schäfer, Lothar; Ramek, Michael; Peeters, Anik; van Alsenoy, Christian

2001-06-01

The conformational properties of N-formyl L-alanine amide (ALA) were investigated using RMP2/6-311G∗∗ ab initio gradient geometry optimization. One hundred forty four structures of ALA were optimized at 30° grid points in its φ(N-C(α)), ψ(C(α)-C‧) conformational space. Using cubic spline functions, the grid structures were then used to construct analytical representations of complete surfaces, in φ,ψ-space, of bond lengths, bond angles, torsional sensitivity and electrostatic atomic charges. Analyses show that, in agreement with previous studies, the right-handed helical conformation, αR, is not a local energy minimum of the potential energy surface of ALA. Comparisons with protein crystallographic data show that the characteristic differences between geometrical trends in dipeptides and proteins, previously found for ab initio dipeptide structures obtained without electron correlation, are also found in the electron-correlated geometries. In contrast to generally accepted features of force fields used in empirical molecular modeling, partial atomic charges obtained by the CHELPG method are found to be not constant, but to vary significantly throughout the φ,ψ-space. By comparing RHF and MP2 structures, the effects of dispersion forces on ALA were studied, revealing molecular contractions for those conformations, in which small adjustments of torsional angles entail large changes in non-bonded distances.

Increasing the wear resistance of ultra-high molecular weight polyethylene by adding solid lubricating fillers

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

Panin, S. V., E-mail: svp@ispms.tsc.ru; Kornienko, L. A.; Poltaranin, M. A.

2014-11-14

In order to compare effectiveness of adding solid lubricating fillers for polymeric composites based on ultra-high molecular weight polyethylene (UHMWPE) with graphite, molybdenum disulfide and polytetrafluoroethylene, their tribotechnical characteristics under dry friction, boundary lubrication and abrasive wearing were investigated. The optimal weight fractions of fillers in terms of improving wear resistance have been determined. The supramolecular structure and topography of wear track surfaces of UHMWPE-based composites with different content of fillers have been studied.

Molecular docking, 3D-QSAR and structural optimization on imidazo-pyridine derivatives dually targeting AT1 and PPARγ

PubMed Central

Zhang, Jun; Hao, Qing-Qing; Liu, Xin; Jing, Zhi; Jia, Wen-Qing; Wang, Shu-Qing; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

2017-01-01

Telmisartan, a bifunctional agent of blood pressure lowering and glycemia reduction, was previously reported to antagonize angiotensin II type 1 (AT1) receptor and partially activate peroxisome proliferator-activated receptor γ (PPARγ) simultaneously. Through the modification to telmisartan, researchers designed and obtained imidazo-\\pyridine derivatives with the IC50s of 0.49∼94.1 nM against AT1 and EC50s of 20∼3640 nM towards PPARγ partial activation. For minutely inquiring the interaction modes with the relevant receptor and analyzing the structure-activity relationships, molecular docking and 3D-QSAR (Quantitative structure-activity relationships) analysis of these imidazo-\\pyridines on dual targets were conducted in this work. Docking approaches of these derivatives with both receptors provided explicit interaction behaviors and excellent matching degree with the binding pockets. The best CoMFA (Comparative Molecular Field Analysis) models exhibited predictive results of q2=0.553, r2=0.954, SEE=0.127, r2pred=0.779 for AT1 and q2=0.503, r2=1.00, SEE=0.019, r2pred=0.604 for PPARγ, respectively. The contour maps from the optimal model showed detailed information of structural features (steric and electrostatic fields) towards the biological activity. Combining the bioisosterism with the valuable information from above studies, we designed six molecules with better predicted activities towards AT1 and PPARγ partial activation. Overall, these results could be useful for designing potential dual AT1 antagonists and partial PPARγ agonists. PMID:28445965

Molecular docking, 3D-QSAR and structural optimization on imidazo-pyridine derivatives dually targeting AT1 and PPARg.

PubMed

Zhang, Jun; Hao, Qing-Qing; Liu, Xin; Jing, Zhi; Jia, Wen-Qing; Wang, Shu-Qing; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

2017-04-11

Telmisartan, a bifunctional agent of blood pressure lowering and glycemia reduction, was previously reported to antagonize angiotensin II type 1 (AT1) receptor and partially activate peroxisome proliferator-activated receptor γ (PPARγ) simultaneously. Through the modification to telmisartan, researchers designed and obtained imidazo-\\pyridine derivatives with the IC50s of 0.49~94.1 nM against AT1 and EC50s of 20~3640 nM towards PPARγ partial activation. For minutely inquiring the interaction modes with the relevant receptor and analyzing the structure-activity relationships, molecular docking and 3D-QSAR (Quantitative structure-activity relationships) analysis of these imidazo-\\pyridines on dual targets were conducted in this work. Docking approaches of these derivatives with both receptors provided explicit interaction behaviors and excellent matching degree with the binding pockets. The best CoMFA (Comparative Molecular Field Analysis) models exhibited predictive results of q2=0.553, r2=0.954, SEE=0.127, r2pred=0.779 for AT1 and q2=0.503, r2=1.00, SEE=0.019, r2pred=0.604 for PPARγ, respectively. The contour maps from the optimal model showed detailed information of structural features (steric and electrostatic fields) towards the biological activity. Combining the bioisosterism with the valuable information from above studies, we designed six molecules with better predicted activities towards AT1 and PPARγ partial activation. Overall, these results could be useful for designing potential dual AT1 antagonists and partial PPARγ agonists.

Scoring of Side-Chain Packings: An Analysis of Weight Factors and Molecular Dynamics Structures.

PubMed

Colbes, Jose; Aguila, Sergio A; Brizuela, Carlos A

2018-02-26

The protein side-chain packing problem (PSCPP) is a central task in computational protein design. The problem is usually modeled as a combinatorial optimization problem, which consists of searching for a set of rotamers, from a given rotamer library, that minimizes a scoring function (SF). The SF is a weighted sum of terms, that can be decomposed in physics-based and knowledge-based terms. Although there are many methods to obtain approximate solutions for this problem, all of them have similar performances and there has not been a significant improvement in recent years. Studies on protein structure prediction and protein design revealed the limitations of current SFs to achieve further improvements for these two problems. In the same line, a recent work reported a similar result for the PSCPP. In this work, we ask whether or not this negative result regarding further improvements in performance is due to (i) an incorrect weighting of the SFs terms or (ii) the constrained conformation resulting from the protein crystallization process. To analyze these questions, we (i) model the PSCPP as a bi-objective combinatorial optimization problem, optimizing, at the same time, the two most important terms of two SFs of state-of-the-art algorithms and (ii) performed a preprocessing relaxation of the crystal structure through molecular dynamics to simulate the protein in the solvent and evaluated the performance of these two state-of-the-art SFs under these conditions. Our results indicate that (i) no matter what combination of weight factors we use the current SFs will not lead to better performances and (ii) the evaluated SFs will not be able to improve performance on relaxed structures. Furthermore, the experiments revealed that the SFs and the methods are biased toward crystallized structures.

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

Sivak, David; Crooks, Gavin

A fundamental problem in modern thermodynamics is how a molecular-scale machine performs useful work, while operating away from thermal equilibrium without excessive dissipation. To this end, we derive a friction tensor that induces a Riemannian manifold on the space of thermodynamic states. Within the linear-response regime, this metric structure controls the dissipation of finite-time transformations, and bestows optimal protocols with many useful properties. We discuss the connection to the existing thermodynamic length formalism, and demonstrate the utility of this metric by solving for optimal control parameter protocols in a simple nonequilibrium model.

Closing loop base pairs in RNA loop-loop complexes: structural behavior, interaction energy and solvation analysis through molecular dynamics simulations.

PubMed

Golebiowski, Jérôme; Antonczak, Serge; Fernandez-Carmona, Juan; Condom, Roger; Cabrol-Bass, Daniel

2004-12-01

Nanosecond molecular dynamics using the Ewald summation method have been performed to elucidate the structural and energetic role of the closing base pair in loop-loop RNA duplexes neutralized by Mg2+ counterions in aqueous phases. Mismatches GA, CU and Watson-Crick GC base pairs have been considered for closing the loop of an RNA in complementary interaction with HIV-1 TAR. The simulations reveal that the mismatch GA base, mediated by a water molecule, leads to a complex that presents the best compromise between flexibility and energetic contributions. The mismatch CU base pair, in spite of the presence of an inserted water molecule, is too short to achieve a tight interaction at the closing-loop junction and seems to force TAR to reorganize upon binding. An energetic analysis has allowed us to quantify the strength of the interactions of the closing and the loop-loop pairs throughout the simulations. Although the water-mediated GA closing base pair presents an interaction energy similar to that found on fully geometry-optimized structure, the water-mediated CU closing base pair energy interaction reaches less than half the optimal value.

Structural and vibrational spectroscopy investigation of the 5-[(diphenyl) amino] isophthalic acid molecule

NASA Astrophysics Data System (ADS)

Kurt, M.; Şaş, E. Babur; Can, M.; Okur, S.; Icli, S.; Demic, S.

2014-10-01

The molecular structure and vibrations of 5-(diphenyl) amino] isophthalic acid (DPIFA) were investigated by different spectroscopic techniques (such as infrared and Raman). FT-IR, FT-Raman and dispersive Raman spectra were recorded in the solid phase. HOMO-LUMO analyses were performed. The theoretical calculations for the molecular structure and spectroscopic studies were performed with DFT (B3LYP) and 6-311G(d,p) basis set calculations using the Gaussian 09 program. After optimizing the geometry of the molecule, vibration wavenumbers and fundamental vibrations wavenumbers were assigned on the basis of the potential energy distribution (PED) of the vibrational modes calculated with VEDA 4 program. The results of theoretical calculations for the spectra of the title compound were compared with the observed spectra.

Structural modeling of Ge6.25As32.5Se61.25 using a combination of reverse Monte Carlo and Ab initio molecular dynamics.

PubMed

Opletal, George; Drumm, Daniel W; Wang, Rong P; Russo, Salvy P

2014-07-03

Ternary glass structures are notoriously difficult to model accurately, and yet prevalent in several modern endeavors. Here, a novel combination of Reverse Monte Carlo (RMC) modeling and ab initio molecular dynamics (MD) is presented, rendering these complicated structures computationally tractable. A case study (Ge6.25As32.5Se61.25 glass) illustrates the effects of ab initio MD quench rates and equilibration temperatures, and the combined approach's efficacy over standard RMC or random insertion methods. Submelting point MD quenches achieve the most stable, realistic models, agreeing with both experimental and fully ab initio results. The simple approach of RMC followed by ab initio geometry optimization provides similar quality to the RMC-MD combination, for far fewer resources.

Methods to enable the design of bioactive small molecules targeting RNA

PubMed Central

Disney, Matthew D.; Yildirim, Ilyas; Childs-Disney, Jessica L.

2014-01-01

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including Structure-Activity Relationships Through Sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome. PMID:24357181

Methods to enable the design of bioactive small molecules targeting RNA.

PubMed

Disney, Matthew D; Yildirim, Ilyas; Childs-Disney, Jessica L

2014-02-21

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including structure-activity relationships through sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome.

A novel series of thiosemicarbazone drugs: From synthesis to structure

NASA Astrophysics Data System (ADS)

Ebrahimi, Hossein Pasha; Hadi, Jabbar S.; Alsalim, Tahseen A.; Ghali, Thaer S.; Bolandnazar, Zeinab

2015-02-01

A new series of thiosemicarbazones (TSCs) and their 1,3,4-thiadiazolines (TDZs) containing acetamide group have been synthesized from thiosemicarbazide compounds by the reaction of TSCs with cyclic ketones as well as aromatic aldehydes. The structures of newly synthesized 1,3,4-thiadiazole derivatives obtained by heterocyclization of the TSCs with acetic anhydride were experimentally characterized by spectral methods using IR, 1H NMR, 13C NMR and mass spectroscopic methods. Furthermore, the structural, thermodynamic, and electronic properties of the studied compounds were also studied theoretically by performing Density Functional Theory (DFT) to access reliable results to the experimental values. The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and Mulliken atomic charges of the studied compounds have been calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from optimized geometry. The theoretical 13C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained.

Mathematical inference and control of molecular networks from perturbation experiments

NASA Astrophysics Data System (ADS)

Mohammed-Rasheed, Mohammed

One of the main challenges facing biologists and mathematicians in the post genomic era is to understand the behavior of molecular networks and harness this understanding into an educated intervention of the cell. The cell maintains its function via an elaborate network of interconnecting positive and negative feedback loops of genes, RNA and proteins that send different signals to a large number of pathways and molecules. These structures are referred to as genetic regulatory networks (GRNs) or molecular networks. GRNs can be viewed as dynamical systems with inherent properties and mechanisms, such as steady-state equilibriums and stability, that determine the behavior of the cell. The biological relevance of the mathematical concepts are important as they may predict the differentiation of a stem cell, the maintenance of a normal cell, the development of cancer and its aberrant behavior, and the design of drugs and response to therapy. Uncovering the underlying GRN structure from gene/protein expression data, e.g., microarrays or perturbation experiments, is called inference or reverse engineering of the molecular network. Because of the high cost and time consuming nature of biological experiments, the number of available measurements or experiments is very small compared to the number of molecules (genes, RNA and proteins). In addition, the observations are noisy, where the noise is due to the measurements imperfections as well as the inherent stochasticity of genetic expression levels. Intra-cellular activities and extra-cellular environmental attributes are also another source of variability. Thus, the inference of GRNs is, in general, an under-determined problem with a highly noisy set of observations. The ultimate goal of GRN inference and analysis is to be able to intervene within the network, in order to force it away from undesirable cellular states and into desirable ones. However, it remains a major challenge to design optimal intervention strategies in order to affect the time evolution of molecular activity in a desirable manner. In this proposal, we address both the inference and control problems of GRNs. In the first part of the thesis, we consider the control problem. We assume that we are given a general topology network structure, whose dynamics follow a discrete-time Markov chain model. We subsequently develop a comprehensive framework for optimal perturbation control of the network. The aim of the perturbation is to drive the network away from undesirable steady-states and to force it to converge to a unique desirable steady-state. The proposed framework does not make any assumptions about the topology of the initial network (e.g., ergodicity, weak and strong connectivity), and is thus applicable to general topology networks. We define the optimal perturbation as the minimum-energy perturbation measured in terms of the Frobenius norm between the initial and perturbed networks. We subsequently demonstrate that there exists at most one optimal perturbation that forces the network into the desirable steady-state. In the event where the optimal perturbation does not exist, we construct a family of sub-optimal perturbations that approximate the optimal solution arbitrarily closely. In the second part of the thesis, we address the inference problem of GRNs from time series data. We model the dynamics of the molecules using a system of ordinary differential equations corrupted by additive white noise. For large-scale networks, we formulate the inference problem as a constrained maximum likelihood estimation problem. We derive the molecular interactions that maximize the likelihood function while constraining the network to be sparse. We further propose a procedure to recover weak interactions based on the Bayesian information criterion. For small-size networks, we investigated the inference of a globally stable 7-gene melanoma genetic regulatory network from genetic perturbation experiments. We considered five melanoma cell lines, who exhibit different motility/invasion behavior under the same perturbation experiment of gene Wnt5a. The results of the simulations validate both the steady state levels and the experimental data of the perturbation experiments of all five cell lines. The goal of this study is to answer important questions that link the response of the network to perturbations, as measured by the experiments, to its structure, i.e., connectivity. Answers to these questions shed novel insights on the structure of networks and how they react to perturbations.

[Strategy of molecular design of drugs: the unification of macro-properties and micro-structures of a molecule].

PubMed

Guo, Zong-Ru

2008-03-01

The interaction of a drug with the organism involves both the disposition of a drug by the organism and the action of a drug on the organism. The disposition of various exogenous substances, including drugs, complies with general rules. The underlying physical and chemical changes to different drugs in view of time and space, i. e. pharmacokinetics, share common characteristics, that is the tout ensemble of a molecule and its macroscopic properties convey direct effect on the pharmacokinetic behavior as the tendency and consequence of biological evolution. The action of a drug on the organism, on the other hand, implicates the physico-chemical binding of a drug molecule to the target protein, which induces pharmacological and toxicological effects. The biological reactions, no matter beneficial or adverse, are all specific and individual manifestation of the drug molecule and determined by the interactive binding between definitive atoms or groups of the drug molecule and the macromolecular target in three-dimension. Such critical atoms, groups, or fragments responsible for the interaction reflect the microscopic structures of drug molecules and are called pharmacophore. In this context, a drug molecule is presumed as an assembly of macroscopic property and microscopic structure, with the macroscopic properties determining the absorption, distribution, metabolism and elimination of drugs and the microscopic structure coining pharmacological action. The knowledge of the internal relationship between macroscopy/microscopy and PK/PD conduces to comprehension of drug action and guides molecular drug design, because this conception facilitates the identification of structural features necessary for biological response, and the determination of factors modulating the physico-chemical and pharmacokinetic properties. The factors determining macro-properties include molecular weight, solubility, charge, lipophilicity (partition), and polar surface area, etc., which are destined by molecular scaffolds and/or side chain(s) apart from pharmacophore. The features of micro-structures contributing to specific activity contain hydrogen bonding donor and acceptor, positive and negative charge centers, hydrophobic centers and centers of aromatic rings. Different combinations and spacial arrangements of these features determine the distinct activity presented. The macro-property and micro-structure are integrated into a single molecule, and are inseparable. The macro-property reflects overall contribution of atoms and groups in the micro-structure. On the other hand, structural changes aimed to adjust macroscopic property usually alter the relative position of the microscopic structure. The goal of molecular drug design is to integrate the macroscopic and microscopic factors in optimized manner. In the early stage of molecular design, both macroscopic property and microscopic structure should be considered to make pharmacodynamics, pharmacokinetics, and physico-chemical properties in optimal match. Therefore, it required the existence of structural overlapping among acceptable pharmacokinetics, visible developing potential and specific pharmacodynamics. The larger the scope of overlapping, the higher the possibility to be a drug.

Fine refinement of solid-state molecular structures of Leu- and Met-enkephalins by NMR crystallography.

PubMed

Pawlak, Tomasz; Potrzebowski, Marek J

2014-03-27

This paper presents a methodology that allows the fine refinement of the crystal and molecular structure for compounds for which the data deposited in the crystallographic bases are of poor quality. Such species belong to the group of samples with molecular disorder. In the Cambridge Crystallographic Data Center (CCDC), there are approximately 22,000 deposited structures with an R-factor over 10. The powerful methodology we present employs crystal data for Leu-enkephalin (two crystallographic forms) with R-factor values of 14.0 and 8.9 and for Met-enkephalin (one form) with an R-factor of 10.5. NMR crystallography was employed in testing the X-ray data and the quality of the structure refinement. The GIPAW (gauge invariant projector augmented wave) method was used to optimize the coordinates of the enkephalins and to compute NMR parameters. As we reveal, this complementary approach makes it possible to generate a reasonable set of new coordinates that better correlate to real samples. This methodology is general and can be employed in the study of each compound possessing magnetically active nuclei.

On the optimal design of molecular sensing interfaces with lipid bilayer assemblies - A knowledge based approach

NASA Astrophysics Data System (ADS)

Siontorou, Christina G.

2012-12-01

Biosensors are analytic devices that incorporate a biochemical recognition system (biological, biologicalderived or biomimic: enzyme, antibody, DNA, receptor, etc.) in close contact with a physicochemical transducer (electrochemical, optical, piezoelectric, conductimetric, etc.) that converts the biochemical information, produced by the specific biological recognition reaction (analyte-biomolecule binding), into a chemical or physical output signal, related to the concentration of the analyte in the measuring sample. The biosensing concept is based on natural chemoreception mechanisms, which are feasible over/within/by means of a biological membrane, i.e., a structured lipid bilayer, incorporating or attached to proteinaceous moieties that regulate molecular recognition events which trigger ion flux changes (facilitated or passive) through the bilayer. The creation of functional structures that are similar to natural signal transduction systems, correlating and interrelating compatibly and successfully the physicochemical transducer with the lipid film that is self-assembled on its surface while embedding the reconstituted biological recognition system, and at the same time manage to satisfy the basic conditions for measuring device development (simplicity, easy handling, ease of fabrication) is far from trivial. The aim of the present work is to present a methodological framework for designing such molecular sensing interfaces, functioning within a knowledge-based system built on an ontological platform for supplying sub-systems options, compatibilities, and optimization parameters.

Synthesis, X-ray diffraction method, spectroscopic characterization (FT-IR, 1H and 13C NMR), antimicrobial activity, Hirshfeld surface analysis and DFT computations of novel sulfonamide derivatives

NASA Astrophysics Data System (ADS)

Demircioğlu, Zeynep; Özdemir, Fethi Ahmet; Dayan, Osman; Şerbetçi, Zafer; Özdemir, Namık

2018-06-01

Synthesized compounds of N-(2-aminophenyl)benzenesulfonamide 1 and (Z)-N-(2-((2-nitrobenzylidene)amino)phenyl)benzenesulfonamide 2 were characterized by antimicrobial activity, FT-IR, 1H and 13C NMR. Two new Schiff base ligands containing aromatic sulfonamide fragment of (Z)-N-(2-((3-nitrobenzylidene)amino)phenyl)benzenesulfonamide 3 and (Z)-N-(2-((4-nitrobenzylidene)amino)phenyl)benzenesulfonamide 4 were synthesized and investigated by spectroscopic techniques including 1H and 13C NMR, FT-IR, single crystal X-ray diffraction, Hirshfeld surface, theoretical method analyses and by antimicrobial activity. The molecular geometry obtained from the X-ray structure determination was optimized Density Functional Theory (DFT/B3LYP) method with the 6-311++G(d,p) basis set in ground state. From the optimized geometry of the molecules of 3 and 4, the geometric parameters, vibrational wavenumbers and chemical shifts were computed. The optimized geometry results, which were well represented the X-ray data, were shown that the chosen of DFT/B3LYP 6-311G++(d,p) was a successful choice. After a successful optimization, frontier molecular orbitals, chemical activity, non-linear optical properties (NLO), molecular electrostatic mep (MEP), Mulliken population method, natural population analysis (NPA) and natural bond orbital analysis (NBO), which cannot be obtained experimentally, were calculated and investigated.

Packing optimization for automated generation of complex system's initial configurations for molecular dynamics and docking.

PubMed

Martínez, José Mario; Martínez, Leandro

2003-05-01

Molecular Dynamics is a powerful methodology for the comprehension at molecular level of many chemical and biochemical systems. The theories and techniques developed for structural and thermodynamic analyses are well established, and many software packages are available. However, designing starting configurations for dynamics can be cumbersome. Easily generated regular lattices can be used when simple liquids or mixtures are studied. However, for complex mixtures, polymer solutions or solid adsorbed liquids (for example) this approach is inefficient, and it turns out to be very hard to obtain an adequate coordinate file. In this article, the problem of obtaining an adequate initial configuration is treated as a "packing" problem and solved by an optimization procedure. The initial configuration is chosen in such a way that the minimum distance between atoms of different molecules is greater than a fixed tolerance. The optimization uses a well-known algorithm for box-constrained minimization. Applications are given for biomolecule solvation, many-component mixtures, and interfaces. This approach can reduce the work of designing starting configurations from days or weeks to few minutes or hours, in an automated fashion. Packing optimization is also shown to be a powerful methodology for space search in docking of small ligands to proteins. This is demonstrated by docking of the thyroid hormone to its nuclear receptor. Copyright 2003 Wiley Periodicals, Inc. J Comput Chem 24: 819-825, 2003

Computational design and multivariate optimization of an electrochemical metoprolol sensor based on molecular imprinting in combination with carbon nanotubes.

PubMed

Nezhadali, Azizollah; Mojarrab, Maliheh

2016-06-14

This work describes the development of an electrochemical sensor based on a new molecularly imprinted polymer for detection of metoprolol (MTP) at ultra-trace level. The polypyrrole (PPy) was electrochemically synthesized on the tip of a pencil graphite electrode (PGE) which modified whit functionalized multi-walled carbon nanotubes (MWCNTs). The fabrication process of the sensor was characterized by cyclic voltammetry (CV) and the measurement process was carried out by differential pulse voltammetry (DPV). A computational approach was used to screening functional monomers and polymerization solvent for rational design of molecularly imprinted polymer (MIP). Based on computational results, pyrrole and water were selected as functional monomer and polymerization solvent, respectively. Several significant parameters controlling the performance of the MIP sensor were examined and optimized using multivariate optimization methods such as Plackett-Burman design (PBD) and central composite design (CCD). Under the selected optimal conditions, MIP sensor was showed a linear range from 0.06 to 490 μmol L(-1) MTP, a limit of detection of 2.88 nmol L(-1), a highly reproducible response (RSD 3.9%) and a good selectivity in the presence of structurally related molecules. Furthermore, the applicability of the method was successfully tested with determination of MTP in real samples (tablet, and serum). Copyright © 2016 Elsevier B.V. All rights reserved.

Chiral micellar electrokinetic chromatography (CMEKC)-atmospheric pressure photoionization of benzoin derivatives using mixed molecular micelles

PubMed Central

He, Jun; Shamsi, Shahab A.

2012-01-01

In the present work we report, for the first time, the successful on-line coupling of chiral micellar electrokinetic chromatography (CMEKC) to atmospheric pressure photo-ionization mass spectrometry (APPI-MS). Four structurally similar neutral test solutes (e.g., benzoin derivatives) were successfully ionized by APPI-MS. The mass spectra in the positive ion mode showed that the protonated molecular ions of benzoins are not the most abundant fragment ions. Simultaneous enantioseparation by CMEKC and on-line APPI-MS detection of four photoinitiators: hydrobenzoin (HBNZ), benzoin (BNZ), benzoin methyl ether (BME), benzoin ethyl ether (BEE), were achieved using an optimized molar ratio of mixed molecular micelle of two polymeric chiral surfactants (polysodium N-undecenoxy carbonyl-L-leucinate and polysodium N-undecenoyl-L,L-leucylvalinate). The CMEKC conditions, such as voltage, chiral polymeric surfactant concentration, buffer pH, and BGE concentration, were optimized using a multivariate central composite design (CCD). The sheath liquid composition (involving % v/v methanol, dopant concentration, electrolyte additive concentration, and flow rate) and spray chamber parameters (drying gas flow rate, drying gas temperature, and vaporizer temperature) were also optimized with CCD. Models built based on the CCD results and response surface method was used to analyze the interactions between factors and their effects on the responses. The final overall optimum conditions for CMEKC-APPI-MS were also predicted and found in agreement with the experimentally optimized parameters. PMID:21500208

Structural Characterization of Vapor-deposited Organic Glasses

NASA Astrophysics Data System (ADS)

Gujral, Ankit

Physical vapor deposition, a common route of thin film fabrication for organic electronic devices, has recently been shown to produce organic glassy films with enhanced kinetic stability and anisotropic structure. Anisotropic structures are of interest in the organic electronics community as it has been shown that certain structures lead to enhanced device performance, such as higher carrier mobility and better light outcoupling. A mechanism proposed to explain the origin of the stability and anisotropy of vapor-deposited glasses relies on two parameters: 1) enhanced molecular mobility at the free surface (vacuum interface) of a glass, and 2) anisotropic molecular packing at the free surface of the supercooled liquid of the glass-forming system. By vapor-depositing onto a substrate maintained at Tsubstrate < Tg (where Tg is the glass transition temperature), the enhanced molecular mobility at the free surface allows every molecule that lands on the surface to at least partially equilibrate to the preferred anisotropic molecular packing motifs before being buried by further deposition. The extent of equilibration depends on the mobility at the surface, controlled by Tsubstrate, and the residence time on the free surface, controlled by the rate of deposition. This body of work deals with the optimization of deposition conditions and system chemistry to prepare and characterize films with functional anisotropic structures. Here, we show that structural anisotropy can be attained for a variety of molecular systems including a rod-shaped non-mesogen, TPD, a rod-shaped smectic mesogen, itraconazole, two discotic mesogens, phenanthroperylene-ester and triphenylene-ester, and a disc-shaped non-mesogen, m-MTDATA. Experimental evidence is also provided of the anisotropic molecular packing at the free surface (vacuum interface) for the disc-shaped systems that are consistent with the expectations of the proposed mechanism and the final bulk state of the vapor-deposited glasses.

Fluorescent sensor systems based on nanostructured polymeric membranes for selective recognition of Aflatoxin B1.

PubMed

Sergeyeva, Tetyana; Yarynka, Daria; Piletska, Elena; Lynnik, Rostyslav; Zaporozhets, Olga; Brovko, Oleksandr; Piletsky, Sergey; El'skaya, Anna

2017-12-01

Nanostructured polymeric membranes for selective recognition of aflatoxin B1 were synthesized in situ and used as highly sensitive recognition elements in the developed fluorescent sensor. Artificial binding sites capable of selective recognition of aflatoxin B1 were formed in the structure of the polymeric membranes using the method of molecular imprinting. A composition of molecularly imprinted polymer (MIP) membranes was optimized using the method of computational modeling. The MIP membranes were synthesized using the non-toxic close structural analogue of aflatoxin B1, ethyl-2-oxocyclopentanecarboxylate as a dummy template. The MIP membranes with the optimized composition demonstrated extremely high selectivity towards aflatoxin B1 (AFB1). Negligible binding of close structural analogues of AFB1 - aflatoxins B2 (AFB2), aflatoxin G2 (AFG2), and ochratoxin A (OTA) was demonstrated. Binding of AFB1 by the MIP membranes was investigated as a function of both type and concentration of the functional monomer in the initial monomer composition used for the membranes' synthesis, as well as sample composition. The conditions of the solid-phase extraction of the mycotoxin using the MIP membrane as a stationary phase (pH, ionic strength, buffer concentration, volume of the solution, ratio between water and organic solvent, filtration rate) were optimized. The fluorescent sensor system based on the optimized MIP membranes provided a possibility of AFB1 detection within the range 14-500ngmL -1 demonstrating detection limit (3Ϭ) of 14ngmL -1 . The developed technique was successfully applied for the analysis of model solutions and waste waters from bread-making plants. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of ground state optical transfer for ultracold alkali dimers

NASA Astrophysics Data System (ADS)

Bouloufa-Maafa, Nadia; Londono, Beatriz; Borsalino, Dimitri; Vexiau, Romain; Mahecha, Jorge; Dulieu, Olivier; Luc-Koenig, Eliane

2013-05-01

Control of molecular states by laser pulses offer promising potential applications. The manipulation of molecules by external fields requires precise knowledge of the molecular structure. Our motivation is to perform a detailed analysis of the spectroscopic properties of alkali dimers, with the aim to determine efficient optical paths to form molecules in the absolute ground state and to determine the optimal parameters of the optical lattices where those molecules are manipulated to avoid losses by collisions. To this end, we use state of the art molecular potentials, R-dependent spin-orbit coupling and transition dipole moment to perform our calculations. R-dependent SO coupling are of crucial importance because the transitions occur at internuclear distances where they are affected by this R-dependence. Efficient schemes to transfer RbCs, KRb and KCs to the absolute ground state as well as the optimal parameters of the optical lattices will be presented. This work was supported in part by ``Triangle de la Physique'' under contract 2008-007T-QCCM (Quantum Control of Cold Molecules).

Targeting CYP51 for drug design by the contributions of molecular modeling.

PubMed

Rabelo, Vitor W; Santos, Taísa F; Terra, Luciana; Santana, Marcos V; Castro, Helena C; Rodrigues, Carlos R; Abreu, Paula A

2017-02-01

CYP51 is an enzyme of sterol biosynthesis pathway present in animals, plants, protozoa and fungi. This enzyme is described as an important drug target that is still of interest. Therefore, in this work, we reviewed the structure and function of CYP51 and explored the molecular modeling approaches for the development of new antifungal and antiprotozoans that target this enzyme. Crystallographic structures of CYP51 of some organisms have already been described in the literature, which enable the construction of homology models of other organisms' enzymes and molecular docking studies of new ligands. The binding mode and interactions of some new series of azoles with antifungal or antiprotozoan activities has been studied and showed important residues of the active site. Molecular modeling is an important tool to be explored for the discovery and optimization of CYP51 inhibitors with better activities, pharmacokinetics, and toxicological profiles. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Highly organized smectic-like packing in vapor-deposited glasses of a liquid crystal

DOE PAGES

Gujral, Ankit; Gomez, Jaritza; Jiang, Jing; ...

2016-12-26

Glasses of a model smectic liquid crystal-forming molecule, itraconazole, were prepared by vapor deposition onto substrates with temperatures ranging from T substrate = 0.78T g to 1.02T g, where T g (=330 K) is the glass transition temperature. The films were characterized using X-ray scattering techniques. For T substrate near and below T g, glasses with layered smectic-like structures can be prepared and the layer spacing can be tuned by 16% through the choice of T substrate. Remarkably, glasses prepared with T substrate values above T g exhibit levels of structural organization much higher than that of a thermally annealedmore » film. These results are explained by a mechanism based upon a preferred molecular orientation and enhanced molecular motion at the free surface, indicating that molecular organization in the glass is independent of the anchoring preferred at the substrate. Furthermore, these results suggest new strategies for optimizing molecular packing within active layers of organic electronic and optoelectronic devices.« less

Capillary waves' dynamics at the nanoscale

NASA Astrophysics Data System (ADS)

Delgado-Buscalioni, Rafael; Chacón, Enrique; Tarazona, Pedro

2008-12-01

We study the dynamics of thermally excited capillary waves (CW) at molecular scales, using molecular dynamics simulations of simple liquid slabs. The analysis is based on the Fourier modes of the liquid surface, constructed via the intrinsic sampling method (Chacón and Tarazona 2003 Phys. Rev. Lett. 91 166103). We obtain the time autocorrelation of the Fourier modes to get the frequency and damping rate Γd(q) of each mode, with wavenumber q. Continuum hydrodynamics predicts \\Gamma (q) \\propto q\\gamma (q) and thus provides a dynamic measure of the q-dependent surface tension, γd(q). The dynamical estimation is much more robust than the structural prediction based on the amplitude of the Fourier mode, γs(q). Using the optimal estimation of the intrinsic surface, we obtain quantitative agreement between the structural and dynamic pictures. Quite surprisingly, the hydrodynamic prediction for CW remains valid up to wavelengths of about four molecular diameters. Surface tension hydrodynamics break down at shorter scales, whereby a transition to a molecular diffusion regime is observed.

Studies on the self-catalyzed Knoevenagel condensation, characterization, DPPH radical scavenging activity, cytotoxicity, and molecular properties of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones using single crystal XRD and DFT techniques

NASA Astrophysics Data System (ADS)

Suresh Kumar, G. S.; Antony Muthu Prabhu, A.; Bhuvanesh, N.

2014-10-01

We have studied the self-catalyzed Knoevenagel condensation, spectral characterization, DPPH radical scavenging activity, cytotoxicity, and molecular properties of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones using single crystal XRD and DFT techniques. In the absence of any catalyst, a series of novel 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones were synthesized using Meldrum’s acid and formylphenoxyaliphatic acid(s) in water. These molecules are arranged in the dimer form through intermolecular H-bonding in the single crystal XRD structure. Compounds have better DPPH radical scavenging activity and cytotoxicity against A431 cancer cell line. The optimized molecular structure, natural bond orbital analysis, electrostatic potential map, HOMO-LUMO energies, molecular properties, and atomic charges of these molecules have been studied by performing DFT/B3LYP/3-21G(*) level of theory in gas phase.

Characterization of 1,5-dimethoxynaphthalene by vibrational spectroscopy (FT-IR and FT-Raman) and density functional theory calculations.

PubMed

Kandasamy, M; Velraj, G; Kalaichelvan, S; Mariappan, G

2015-01-05

In this work, we reported a combined experimental and theoretical study on molecular structure, vibrational spectra and natural bond orbital (NBO) analysis of 1,5-dimethoxynaphthalene. The optimized molecular structure, atomic charges, vibrational frequencies and natural bond orbital analysis of 1,5-dimethoxynaphthalene have been studied by performing DFT/B3LYP/6-31G(d,p) level of theory. The FTIR, FT-Raman spectra were recorded in the region of 4000-400 cm(-1) and 3500-50 cm(-1) respectively. The scaled wavenumbers are compared with the experimental values. The difference between the observed and scaled wavenumber values of the most fundamentals is very small. The formation of hydrogen bond was investigated in terms of the charge density by the NBO analysis. Natural Population Analysis (NPA) was used for charge determination in the title molecule. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis were investigated using theoretical calculations. Copyright © 2014 Elsevier B.V. All rights reserved.

Biosynthesis of inulin from sucrose using inulosucrase from Lactobacillus gasseri DSM 20604.

PubMed

Ni, Dawei; Zhu, Yingying; Xu, Wei; Bai, Yuxiang; Zhang, Tao; Mu, Wanmeng

2018-04-01

Inulin is composed of fructose residues connected by β-(2, 1) glycosidic linkages with many promising physiochemical and physiological properties. In this study, an inulin-producing inulosucrase gene from Lactobacillus gasseri DSM 20604 was cloned, expressed and purified. SDS-PAGE and gel filtration found that the recombinant inulosucrase is a monomeric protein with a molecular weight of 63KDa. The optimal pH for its sucrose hydrolysis and transfructosylation activities was pH 5.5. The optimal temperatures were measured to be 45, 25, and 35°C for sucrose hydrolysis, transfructosylation, and total activity, respectively. Biosynthesis studies showed that the optimal enzyme dosage was 4.5U/g sucrose. Higher sucrose concentrations immensely contributed to inulin biosynthesis; the inulin yield reached its maximum after 1.5h of reaction. Structural analyses of the polysaccharide produced by the recombinant enzyme from sucrose revealed that it is an inulin-type fructan with a molecular weight of 5.858×10 6 Da. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering controllable bidirectional molecular motors based on myosin

PubMed Central

Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

2012-01-01

Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells1, and have potential applications in molecular detection and diagnostic devices2,3. Engineering molecular motors with dynamically controllable properties will allow selective perturbation of mechanical processes in living cells, and yield optimized device components for complex tasks such as molecular sorting and directed assembly3. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions4,5 and other signals6. Here we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies7–11 and guided by a structural model12 for the redirected power stroke of myosin VI, we constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our general strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should enable spatiotemporal control over a range of motor properties including processivity, stride size13, and branchpoint turning14. PMID:22343382

Engineering controllable bidirectional molecular motors based on myosin

NASA Astrophysics Data System (ADS)

Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

2012-04-01

Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

Novel pyrazolyl-s-triazine derivatives, molecular structure and antimicrobial activity

NASA Astrophysics Data System (ADS)

Sharma, Anamika; Ghabbour, Hazem; Khan, Shams Tabrez; de la Torre, Beatriz G.; Albericio, Fernando; El-Faham, Ayman

2017-10-01

A new series of pyrazole-containing s-triazine derivatives were synthesized by reaction of the corresponding s-triazinyl hydrazine derivatives with acetylacetone in the presence of HClO4 or DMF/TEA. The former method allowed the preparation of the target products with higher yields. All compounds were fully characterized. X-ray single crystal diffraction for two representative compounds (4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine and N-benzyl-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine) was studied and the molecular structures were optimized using the DFT/B3LYP method. The structures were found to be in agreement with X-ray structures. The antimicrobial and antifungal activity of the prepared compounds were tested against the growth of several microorganisms.

Structural studies of homoisoflavonoids: NMR spectroscopy, X-ray diffraction, and theoretical calculations

NASA Astrophysics Data System (ADS)

Sievänen, Elina; Toušek, Jaromír; Lunerová, Kamila; Marek, Jaromír; Jankovská, Dagmar; Dvorská, Margita; Marek, Radek

2010-08-01

In this article we present a detailed structural investigation for five homoisoflavonoids, molecules important from the pharmacological point of view. For studying the electron distribution as well as its influence on the physicochemical properties, NMR spectroscopy, X-ray diffraction, and theoretical calculations have been used. Nuclear magnetic shieldings obtained by using DFT calculations for optimized molecular geometries are correlated with the experimentally determined chemical shifts. The theoretical data are well in agreement with the experimental values. The single crystal X-ray structures of homoisoflavonoid derivatives 1, 3, and 4 have been solved. The molecular geometries and crystal packing determined by X-ray diffraction are used for characterizing the intermolecular interactions. Electron distribution is crucial for the stability of radicals and hence the antioxidant efficiency of flavonoid structures. The hydrogen bonding governs the formation of complexes of homoisoflavonoids with biological targets.

Insights into the structure of covalently bound fatty acid monolayers on a simplified model of the hair epicuticle from molecular dynamics simulations.

PubMed

Cheong, Daniel W; Lim, Freda C H; Zhang, Liping

2012-09-11

The epicuticle is the outermost layer of the human hair, and consists of a monolayer of fatty acids that is predominantly 18-methyleicosanoic acid (18-MEA) covalently bound to a protein matrix. Surprisingly, despite the clear scientific and industrial importance, the detailed molecular structure of this fatty acid layer is still poorly understood. In this work, we aim to gain insight into the structure of this so-called F-layer by performing molecular dynamics simulations on a simplified hair surface model consisting of a monolayer of 18-MEA covalently attached to graphene sheets at various separation distances. The relative free energy of the fatty acid layer was calculated as a function of separation distance in order to obtain the optimal packing density of the fatty acids. Conformational properties such as the thickness, tilt angle, and order parameter of the fatty acid layers were also calculated to characterize the structure of the F-layer. Simulations of the structurally similar eicosanoic acid (EA) were also performed as a comparison and to investigate the role of the anteiso-methyl side chain at the 18th position of 18-MEA. The degree of water penetration into the fatty acid layer at the various separation distances was also investigated. Our simulations suggest that the optimal spacing for the fatty acids is between 0.492 and 0.651 nm, in contrast to the generally accepted literature value of around 0.9-1.0 nm. This results in a packing density of between 0.21 and 0.37 nm(2) per fatty acid molecule and a thickness of around 2.01-2.64 nm. We also show that, at larger separation distances, the 18-MEA fatty acid provides a slightly better hydrophobic layer than the EA fatty acid, suggesting that the 18-MEA fatty acid may have been naturally selected to provide better protection for the hair when it loses some of the fatty acids due to daily wear and tear. To our knowledge, this is the first attempt to systematically investigate the hair surface structure and properties with molecular simulations.

Method development for compositional analysis of low molecular weight poly(vinyl acetate) by matrix-assisted/laser desorption-mass spectrometry and its application to analysis of chewing gum.

PubMed

Tisdale, Evgenia; Wilkins, Charles

2014-04-11

The influence of the sample preparation parameters (the choice of the solvent and of the matrix:analyte ratio) was investigated and optimal conditions were established for MALDI mass spectrometry analysis of the pristine low molecular weight polyvinyl acetate (PVAc). It was demonstrated that comparison of polymer's and solvent's Hansen solubility parameters could be used as a guide when choosing the solvent for MALDI sample preparation. The highest intensity PVAc signals were obtained when ethyl acetate was used as a solvent along with the lowest matrix-analyte ratio (2,5-dihydroxybenzoic acid was used as a matrix in all experiments). The structure of the PVAc was established with high accuracy using the matrix-assisted laser desorption/ionization-Fourier transform mass spectrometry (MALDI-FTMS) analysis. It was demonstrated that PVAc undergoes unimolecular decomposition by losing acetic acid molecules from its backbone under the conditions of FTMS measurements. Number and weight average molecular weights as well as polydispersity indices were determined with both MALDI-TOF and MALDI-FTMS methods. The sample preparation protocol developed was applied to the analysis of a chewing gum and the molecular weight and structure of the polyvinyl acetate present in the sample were established. Thus, it was shown that optimized MALDI mass spectrometry could be used successfully for characterization of polyvinyl acetate in commercially available chewing gum. Copyright © 2014 Elsevier B.V. All rights reserved.

Hybrid optimal descriptors as a tool to predict skin sensitization in accordance to OECD principles.

PubMed

Toropova, Alla P; Toropov, Andrey A

2017-06-05

Skin sensitization (allergic contact dermatitis) is a widespread problem arising from the contact of chemicals with the skin. The detection of molecular features with undesired effect for skin is complex task owing to unclear biochemical mechanisms and unclearness of conditions of action of chemicals to skin. The development of computational methods for estimation of this endpoint in order to reduce animal testing is recommended (Cosmetics Directive EC regulation 1907/2006; EU Regulation, Regulation, 1223/2009). The CORAL software (http://www.insilico.eu/coral) gives good predictive models for the skin sensitization. Simplified molecular input-line entry system (SMILES) together with molecular graph are used to represent the molecular structure for these models. So-called hybrid optimal descriptors are used to establish quantitative structure-activity relationships (QSARs). The aim of this study is the estimation of the predictive potential of the hybrid descriptors. Three different distributions into the training (≈70%), calibration (≈15%), and validation (≈15%) sets are studied. QSAR for these three distributions are built up with using the Monte Carlo technique. The statistical characteristics of these models for external validation set are used as a measure of predictive potential of these models. The best model, according to the above criterion, is characterized by n validation =29, r 2 validation =0.8596, RMSE validation =0.489. Mechanistic interpretation and domain of applicability for these models are defined. Copyright © 2017 Elsevier B.V. All rights reserved.

Spontaneous formation of polyglutamine nanotubes with molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Laghaei, Rozita; Mousseau, Normand

2010-04-01

Expansion of polyglutamine (polyQ) beyond the pathogenic threshold (35-40 Gln) is associated with several neurodegenerative diseases including Huntington's disease, several forms of spinocerebellar ataxias and spinobulbar muscular atrophy. To determine the structure of polyglutamine aggregates we perform replica-exchange molecular dynamics simulations coupled with the optimized potential for effective peptide forcefield. Using a range of temperatures from 250 to 700 K, we study the aggregation kinetics of the polyglutamine monomer and dimer with chain lengths from 30 to 50 residues. All monomers show a similar structural change at the same temperature from α-helical structure to random coil, without indication of any significant β-strand. For dimers, by contrast, starting from random structures, we observe spontaneous formation of antiparallel β-sheets and triangular and circular β-helical structures for polyglutamine with 40 residues in a 400 ns 50 temperature replica-exchange molecular dynamics simulation (total integrated time 20 μs). This ˜32 Å diameter structure reorganizes further into a tight antiparallel double-stranded ˜22 Å nanotube with 22 residues per turn close to Perutz' model for amyloid fibers as water-filled nanotubes. This diversity of structures suggests the existence of polymorphism for polyglutamine with possibly different pathways leading to the formation of toxic oligomers and to fibrils.

Identifying Novel Molecular Structures for Advanced Melanoma by Ligand-Based Virtual Screening

PubMed Central

Wang, Zhao; Lu, Yan; Seibel, William; Miller, Duane D.; Li, Wei

2009-01-01

We recently discovered a new class of thiazole analogs that are highly potent against melanoma cells. To expand the structure-activity relationship study and to explore potential new molecular scaffolds, we performed extensive ligand-based virtual screening against a compound library containing 342,910 small molecules. Two different approaches of virtual screening were carried out using the structure of our lead molecule: 1) connectivity-based search using Scitegic Pipeline Pilot from Accelerys and 2) molecular shape similarity search using Schrodinger software. Using a testing compound library, both approaches can rank similar compounds very high and rank dissimilar compounds very low, thus validating our screening methods. Structures identified from these searches were analyzed, and selected compounds were tested in vitro to assess their activity against melanoma cancer cell lines. Several molecules showed good anticancer activity. While none of the identified compounds showed better activity than our lead compound, they provided important insight into structural modifications for our lead compound and also provided novel platforms on which we can optimize new classes of anticancer compounds. One of the newly synthesized analogs based on this virtual screening has improved potency and selectivity against melanoma. PMID:19445498

DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015

NASA Astrophysics Data System (ADS)

Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

2016-09-01

Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015.

PubMed

Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

2016-09-01

Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building.

PubMed

Dupradeau, François-Yves; Pigache, Adrien; Zaffran, Thomas; Savineau, Corentin; Lelong, Rodolphe; Grivel, Nicolas; Lelong, Dimitri; Rosanski, Wilfried; Cieplak, Piotr

2010-07-28

Deriving atomic charges and building a force field library for a new molecule are key steps when developing a force field required for conducting structural and energy-based analysis using molecular mechanics. Derivation of popular RESP charges for a set of residues is a complex and error prone procedure because it depends on numerous input parameters. To overcome these problems, the R.E.D. Tools (RESP and ESP charge Derive, ) have been developed to perform charge derivation in an automatic and straightforward way. The R.E.D. program handles chemical elements up to bromine in the periodic table. It interfaces different quantum mechanical programs employed for geometry optimization and computing molecular electrostatic potential(s), and performs charge fitting using the RESP program. By defining tight optimization criteria and by controlling the molecular orientation of each optimized geometry, charge values are reproduced at any computer platform with an accuracy of 0.0001 e. The charges can be fitted using multiple conformations, making them suitable for molecular dynamics simulations. R.E.D. allows also for defining charge constraints during multiple molecule charge fitting, which are used to derive charges for molecular fragments. Finally, R.E.D. incorporates charges into a force field library, readily usable in molecular dynamics computer packages. For complex cases, such as a set of homologous molecules belonging to a common family, an entire force field topology database is generated. Currently, the atomic charges and force field libraries have been developed for more than fifty model systems and stored in the RESP ESP charge DDataBase. Selected results related to non-polarizable charge models are presented and discussed.

Molecular Structure and Chirality Determination from Pulsed-Jet Fourier Transform Microwave Spectroscopy

NASA Astrophysics Data System (ADS)

Lobsiger, Simon; Perez, Cristobal; Evangelisti, Luca; Seifert, Nathan A.; Pate, Brooks; Lehmann, Kevin

2014-06-01

Fourier transform microwave (FTMW) spectroscopy has been used for many years as one of the most accurate methods to determine gas-phase structures of molecules and small molecular clusters. In the last years two pioneering works ushered in a new era applications. First, by exploiting the reduced measurement time and the high sensitivity, the development of chirped-pulse CP-FTMW spectrometers enabled the full structural determination of molecules of increasing size as well as molecular clusters. Second, and more recently, Patterson et al. showed that rotational spectroscopy can also be used for enantiomer-specific detection. Here we present an experimental approach that combines both in a single spectrometer. This set-up is capable to rapidly obtain the full heavy-atom substitution structure using the CP-FTMW features. The inclusion of an extra set of broadband horns allows for a chirality-sensitive measurement of the sample. The measurement we implement is a three-wave mixing experiment that uses time-separated pulses to optimally create the chiral coherence - an approach that was proposed recently. Using samples of R-, S- and racemic Solketal, the physical properties of the three-wave mixing experiment were studied. This involved the measurement of the corresponding nutation curves (molecular signal intensity vs excitation pulse duration) to demonstrate the optimal pulse sequence. The phase stability of the chiral signal, required to assign the absolute stereochemistry, has been studied as a function of the measurement signal-to-noise ratio using a "phasogram" method. G. G. Brown, B. C. Dian, K. O. Douglass, S. M. Geyer, S. T. Shipman, B. H. Pate, Rev. Sci. Instrum. 2008, 79, 053103. D. Patterson, M. Schnell, J. M. Doyle, Nature 2013, 497, 475-477. D. Patterson, J. M. Doyle, Phys. Rev. Lett. 2013, 111, 023008. V. A. Shubert, D. Schmitz, D. Patterson, J. M. Doyle, M. Schnell, Angew. Chem. Int. Ed. 2014, 53, 1152-1155. J.-U. Grabow, Angew. Chem. 2013, 125, 11914 - 11916; Angew. Chem. Int. Ed. 2013, 52, 11698 -11700.

Structural connotations of bioactivity in a series of organophosphinates

NASA Astrophysics Data System (ADS)

King, James W.; Molnar, Stephen P.

Pretreatment before exposure is one of the options for temporarily protecting persons liable to exposure to toxic organophosphorus compounds in agricultural or warfare situations. It is known that organophosphinates interact with neuronal cholinesterases, but that the latter may spontaneously reactivate in time. Before that reactivation, the enzyme is protected against comlexation with organophosphates. In this study, geometrically optimized unitary molecular indices, i.e., the molecular transforms, FTm, FTe, and FTc, indicating general, electronic, and charge properties, respectively, and the analogous normalized molecular moments, Mn, Me, and Mc, were calculated for a number of phosphinates. These indices were subsequently used in correlation trials with spontaneous reactivation percentages at specific elapsed times, as well as in clustering procedures, to evaluate the effect of structure variations on the reactivation percentages. The results of these studies are discussed, as is the effect of the octanol/water partition coefficient on the noted bioactivity.

Molecular design and MD simulations of epitaxial superlattice of self-assembling ternary lipid bilayers

NASA Astrophysics Data System (ADS)

Chou, George; Vaughn, Mark; Cheng, K.

2011-10-01

Multicomponent lipid bilayers represent an important model system for studying cell membranes. At present, an ordered multicomponent phospholipid/cholesterol bilayer system involving charged lipid is still not available. Using a lipid superlattice (SL) model, a 13 x 15 x 15 nm^3 ternary phosphatidylcholine/phosphatidylserine/cholesterol bilayer system in water with simultaneous headgroup SL and acyl chain SL at different depths, or epitaxial SL, of the bilayer has been designed with atomistic detail. The arrangements of this epitaxial SL system were optimized by only two molecular parameters, lattice space and rotational angle of the lipids. Using atomistic MD simulations, we demonstrated the stability of the ordered structures for more than 100 ns. A positional restrained system was also used as a control. This system will provide new insights into understanding the nanodomain structures of cell membranes at the molecular level.

Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate.

PubMed

Maund, Sophia Lisette; Nolley, Rosalie; Peehl, Donna Mae

2014-02-01

Few preclinical models accurately depict normal human prostate tissue or primary prostate cancer (PCa). In vitro systems typically lack complex cellular interactions among structured prostatic epithelia and a stromal microenvironment, and genetic and molecular fidelity are concerns in both in vitro and in vivo models. 'Tissue slice cultures' (TSCs) provide realistic preclinical models of diverse tissues and organs, but have not been fully developed or widely utilized for prostate studies. Problems encountered include degeneration of differentiated secretory cells, basal cell hyperplasia, and poor survival of PCa. Here, we optimized, characterized, and applied a TSC model of primary human PCa and benign prostate tissue that overcomes many deficiencies of current in vitro models. Tissue cores from fresh prostatectomy specimens were precision-cut at 300 μm and incubated in a rotary culture apparatus. The ability of varied culture conditions to faithfully maintain benign and cancer cell and tissue structure and function over time was evaluated by immunohistological and biochemical assays. After optimization of the culture system, molecular and cellular responses to androgen ablation and to piperlongumine (PL), purported to specifically reduce androgen signaling in PCa, were investigated. Optimized culture conditions successfully maintained the structural and functional fidelity of both benign and PCa TSCs for 5 days. TSCs exhibited androgen dependence, appropriately undergoing ductal degeneration, reduced proliferation, and decreased prostate-specific antigen expression upon androgen ablation. Further, TSCs revealed cancer-specific reduction of androgen receptor and increased apoptosis upon treatment with PL, validating data from cell lines. We demonstrate a TSC model that authentically recapitulates the structural, cellular, and genetic characteristics of the benign and malignant human prostate, androgen dependence of the native tissue, and cancer-specific response to a potentially new therapeutic for PCa. The work described herein provides a basis for advancing the experimental utility of the TSC model.

Synthesis, structural and vibrational investigation on 2-phenyl-N-(pyrazin-2-yl)acetamide combining XRD diffraction, FT-IR and NMR spectroscopies with DFT calculations.

PubMed

Lukose, Jilu; Yohannan Panicker, C; Nayak, Prakash S; Narayana, B; Sarojini, B K; Van Alsenoy, C; Al-Saadi, Abdulaziz A

2015-01-25

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-phenyl-N-(pyrazin-2-yl)acetamide have been investigated experimentally and theoretically using Gaussian09 software package. The title compound was optimized by using the HF/6-31G(6D,7F) and B3LYP/6-31G(6D,7F) calculations. The geometrical parameters are in agreement with the XRD data. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Gauge-including atomic orbital (1)H-NMR chemical shifts calculations were carried out and compared with experimental data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular electrostatic potential was performed by the DFT method. First hyperpolarizability is calculated in order to find its role in non linear optics. From the XRD data, in the crystal, molecules are held together by strong C-H⋯O and N-H⋯O intermolecular interactions. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation and optimization of virtual screening workflows with DEKOIS 2.0--a public library of challenging docking benchmark sets.

PubMed

Bauer, Matthias R; Ibrahim, Tamer M; Vogel, Simon M; Boeckler, Frank M

2013-06-24

The application of molecular benchmarking sets helps to assess the actual performance of virtual screening (VS) workflows. To improve the efficiency of structure-based VS approaches, the selection and optimization of various parameters can be guided by benchmarking. With the DEKOIS 2.0 library, we aim to further extend and complement the collection of publicly available decoy sets. Based on BindingDB bioactivity data, we provide 81 new and structurally diverse benchmark sets for a wide variety of different target classes. To ensure a meaningful selection of ligands, we address several issues that can be found in bioactivity data. We have improved our previously introduced DEKOIS methodology with enhanced physicochemical matching, now including the consideration of molecular charges, as well as a more sophisticated elimination of latent actives in the decoy set (LADS). We evaluate the docking performance of Glide, GOLD, and AutoDock Vina with our data sets and highlight existing challenges for VS tools. All DEKOIS 2.0 benchmark sets will be made accessible at http://www.dekois.com.

Protein folding optimization based on 3D off-lattice model via an improved artificial bee colony algorithm.

PubMed

Li, Bai; Lin, Mu; Liu, Qiao; Li, Ya; Zhou, Changjun

2015-10-01

Protein folding is a fundamental topic in molecular biology. Conventional experimental techniques for protein structure identification or protein folding recognition require strict laboratory requirements and heavy operating burdens, which have largely limited their applications. Alternatively, computer-aided techniques have been developed to optimize protein structures or to predict the protein folding process. In this paper, we utilize a 3D off-lattice model to describe the original protein folding scheme as a simplified energy-optimal numerical problem, where all types of amino acid residues are binarized into hydrophobic and hydrophilic ones. We apply a balance-evolution artificial bee colony (BE-ABC) algorithm as the minimization solver, which is featured by the adaptive adjustment of search intensity to cater for the varying needs during the entire optimization process. In this work, we establish a benchmark case set with 13 real protein sequences from the Protein Data Bank database and evaluate the convergence performance of BE-ABC algorithm through strict comparisons with several state-of-the-art ABC variants in short-term numerical experiments. Besides that, our obtained best-so-far protein structures are compared to the ones in comprehensive previous literature. This study also provides preliminary insights into how artificial intelligence techniques can be applied to reveal the dynamics of protein folding. Graphical Abstract Protein folding optimization using 3D off-lattice model and advanced optimization techniques.

Structural Changes Due to Antagonist Binding in Ligand Binding Pocket of Androgen Receptor Elucidated Through Molecular Dynamics Simulations.

PubMed

Sakkiah, Sugunadevi; Kusko, Rebecca; Pan, Bohu; Guo, Wenjing; Ge, Weigong; Tong, Weida; Hong, Huixiao

2018-01-01

When a small molecule binds to the androgen receptor (AR), a conformational change can occur which impacts subsequent binding of co-regulator proteins and DNA. In order to accurately study this mechanism, the scientific community needs a crystal structure of the Wild type AR (WT-AR) ligand binding domain, bound with antagonist. To address this open need, we leveraged molecular docking and molecular dynamics (MD) simulations to construct a structure of the WT-AR ligand binding domain bound with antagonist bicalutamide. The structure of mutant AR (Mut-AR) bound with this same antagonist informed this study. After molecular docking analysis pinpointed the suitable binding orientation of a ligand in AR, the model was further optimized through 1 μs of MD simulations. Using this approach, three molecular systems were studied: (1) WT-AR bound with agonist R1881, (2) WT-AR bound with antagonist bicalutamide, and (3) Mut-AR bound with bicalutamide. Our structures were very similar to the experimentally determined structures of both WT-AR with R1881 and Mut-AR with bicalutamide, demonstrating the trustworthiness of this approach. In our model, when WT-AR is bound with bicalutamide, Val716/Lys720/Gln733, or Met734/Gln738/Glu897 move and thus disturb the positive and negative charge clumps of the AF2 site. This disruption of the AF2 site is key for understanding the impact of antagonist binding on subsequent co-regulator binding. In conclusion, the antagonist induced structural changes in WT-AR detailed in this study will enable further AR research and will facilitate AR targeting drug discovery.

Molecular simulations of electrolyte structure and dynamics in lithium-sulfur battery solvents

NASA Astrophysics Data System (ADS)

Park, Chanbum; Kanduč, Matej; Chudoba, Richard; Ronneburg, Arne; Risse, Sebastian; Ballauff, Matthias; Dzubiella, Joachim

2018-01-01

The performance of modern lithium-sulfur (Li/S) battery systems critically depends on the electrolyte and solvent compositions. For fundamental molecular insights and rational guidance of experimental developments, efficient and sufficiently accurate molecular simulations are thus in urgent need. Here, we construct a molecular dynamics (MD) computer simulation model of representative state-of-the art electrolyte-solvent systems for Li/S batteries constituted by lithium-bis(trifluoromethane)sulfonimide (LiTFSI) and LiNO3 electrolytes in mixtures of the organic solvents 1,2-dimethoxyethane (DME) and 1,3-dioxolane (DOL). We benchmark and verify our simulations by comparing structural and dynamic features with various available experimental reference systems and demonstrate their applicability for a wide range of electrolyte-solvent compositions. For the state-of-the-art battery solvent, we finally calculate and discuss the detailed composition of the first lithium solvation shell, the temperature dependence of lithium diffusion, as well as the electrolyte conductivities and lithium transference numbers. Our model will serve as a basis for efficient future predictions of electrolyte structure and transport in complex electrode confinements for the optimization of modern Li/S batteries (and related devices).

Experimental and theoretical spectroscopic studies of anticancer drug rosmarinic acid using HF and density functional theory.

PubMed

Mariappan, G; Sundaraganesan, N; Manoharan, S

2012-11-01

In this work, we reported a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of anticancer drug of rosmarinic acid. The optimized molecular structure, atomic charges, vibrational frequencies, natural bond orbital analysis and ultraviolet-visible spectral interpretation of rosmarinic acid have been studied by performing HF and DFT/B3LYP/6-31G(d,p) level of theory. The FT-IR (solid and solution phase), FT-Raman (solid phase) spectra were recorded in the region 4000-400 and 3500-50 cm(-1), respectively. The UV-Visible absorption spectra of the compound that dissolved in ethanol were recorded in the range of 200-800 nm. The scaled wavenumbers are compared with the experimental values. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The formation of hydrogen bond was investigated in terms of the charge density by the NBO calculations. Based on the UV spectra and TD-DFT calculations, the electronic structure and the assignments of the absorption bands were carried out. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis were investigated using theoretical calculations. Copyright © 2012 Elsevier B.V. All rights reserved.

Learning To Fold Proteins Using Energy Landscape Theory

PubMed Central

Schafer, N.P.; Kim, B.L.; Zheng, W.; Wolynes, P.G.

2014-01-01

This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy landscape theory of protein folding. We also present a review of the results of the AMH/AMC/AMW/AWSEM family of coarse-grained molecular dynamics protein folding models to illustrate the points covered in the first part of the article. Accurate coarse-grained structure prediction models can be used to investigate a wide range of conceptual and mechanistic issues outside of protein structure prediction; specifically, the paper concludes by reviewing how AWSEM has in recent years been able to elucidate questions related to the unusual kinetic behavior of artificially designed proteins, multidomain protein misfolding, and the initial stages of protein aggregation. PMID:25308991

Pectinase hydrolysis of Dendrobium huoshanense polysaccharide and its effect on protein nonenzymatic glycation.

PubMed

Zha, Xue-Qiang; Li, Xiao-Long; Zhang, Hai-Lin; Cui, Shao-Hua; Liu, Jian; Wang, Jun-Hui; Pan, Li-Hua; Luo, Jian-Ping

2013-10-01

The aim of this study was to investigate the inhibitory effects of molecular weight alteration of Dendrobium huoshanense polysaccharide on protein nonenzymatic glycation. For this purpose, one homogeneous active polysaccharide DHPD1 with molecular weight 3.2 kDa was extracted from D. huoshanense. GC analysis showed that DHPD1 was mainly composed of glucose, arabinose, galactose in a molar ratio of 0.023:1.023:0.021 with a trace of mannose and xylose. In order to get DHPD1-derived fragments with different molecular weight, response surface methodology was employed to optimize the enzymatic degradation conditions. The maximum reducing sugar production (0.399 mg/mL) was obtained under an optimal condition including pectinase dosage 126 U/mL, reaction pH 4.46 and reaction temperature 48 °C. By applying this condition, three DHPD1-derived fragments with different molecular weights were obtained through changing the hydrolysis time. Infrared spectroscopy analysis indicated that the backbone structure of DHPD1 was not destroyed by pectinase hydrolysis. Monosaccharide composition analysis showed that pectinase preferred to liberate glucose from DHPD1. The inhibitory action of DHPD1 on protein nonenzymatic glycation reduced with the decrease of molecular weight. Copyright © 2013 Elsevier B.V. All rights reserved.

Spectroscopic (FT-IR and UV-Vis) and theoretical (HF and DFT) investigation of 2-Ethyl-N-[(5-nitrothiophene-2-yl)methylidene]aniline

NASA Astrophysics Data System (ADS)

Ceylan, Ümit; Tarı, Gonca Özdemir; Gökce, Halil; Ağar, Erbil

2016-04-01

Crystal structure of the title compound, 2-Ethyl-N-[(5-nitrothiophene-2-yl)methylidene]aniline, C13H12N2O2S, has been synthesized and characterized by FT-IR and UV-Vis spectrum. The compound crystallized in the monoclinic space group P 21/c with a = 11.3578 (4) Å, b = 7.4923 (2) Å, c = 14.9676 (6) Å and β = 99.589 (3)° and Z = 4 in the unit cell. The molecular geometry was also calculated using the Gaussian 03 software and structure was optimized using the HF and DFT/B3LYP methods with the 6-311++G(d,p) basis set in ground state. Using the TD-DFT method, the electronic absorption spectra of the title compound was computed in both the gas phase and ethanol solvent. The harmonic vibrational frequencies of the title compound were calculated using the same methods with the 6-311++G(d,p) basis set. The calculated results were compared with the experimental determination results of the compound. It was seen that the optimized structure was in excellent agreement with the X-ray crystal structure. The energetic behaviors of the title compound in solvent media were examined using the HF and DFT/B3LYP methods with the 6-311++G(d,p) basis set applying the polarizable continuum model (PCM). In addition, the molecular orbitals (FMOs) analysis, molecular electrostatic potential (MEP), nonlinear optical and thermodynamic properties of the title compound were performed using the same methods with the 6-311++G(d,p) basis set.

Experimental (X-ray, FT-IR and UV-vis spectra) and theoretical methods (DFT study) of (E)-3-methoxy-2-[(p-tolylimino)methyl]phenol.

PubMed

Demircioğlu, Zeynep; Albayrak, Çiğdem; Büyükgüngör, Orhan

2014-07-15

A suitable single crystal of (E)-3-methoxy-2-[(p-tolylimino)methyl]phenol, formulated as C15H15N1O2, reveals that the structure is adopted to its E configuration about the azomethine C=N double bond. The compound adopts a enol-imine tautomeric form with a strong intramolecular O-H⋯N hydrogen bond. The single crystal X-ray diffraction analysis at 296K crystallizes in the monoclinic space group P21/c with a = 13.4791(11) Å, b = 6.8251(3) Å, c = 18.3561(15) Å, α = 90°, β = 129.296(5)°, γ = 90° and Z = 4. Comprehensive theoretical and experimental structural studies on the molecule have been carried out by FT-IR and UV-vis spectrometry. Optimized molecular structure and harmonic vibrational frequencies have been investigated by DFT/B3LYP method with 6-31G(d,p) basis set. Stability of the molecule, hyperconjugative interactions, charge delocalization and intramolecular hydrogen bond has been analyzed by using natural bond orbital (NBO) analysis. Electronic structures were discussed by TD-DFT method and the relocation of the electron density were determined. The energetic behavior of the title compound has been examined in solvent media using polarizable continuum model (PCM). Molecular electrostatic potential (MEP), Mulliken population method and natural population analysis (NPA) have been studied. Nonlinear optical (NLO) properties were also investigated. In addition, frontier molecular orbitals analysis have been performed from the optimized geometry. An ionization potential (I), electron affinity (A), electrophilicity index (ω), chemical potential (μ), electronegativity (χ), hardness (η), and softness (S), have been investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular replacement: tricks and treats

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

Abergel, Chantal, E-mail: chantal.abergel@igs.cnrs-mrs.fr

2013-11-01

To be successful, molecular replacement relies on the quality of the model and of the crystallographic data. Some tricks that could be applied to the models or to the crystal to increase the success rate of MR are discussed here. Molecular replacement is the method of choice for X-ray crystallographic structure determination provided that suitable structural homologues are available in the PDB. Presently, there are ∼80 000 structures in the PDB (8074 were deposited in the year 2012 alone), of which ∼70% have been solved by molecular replacement. For successful molecular replacement the model must cover at least 50% ofmore » the total structure and the C{sub α} r.m.s.d. between the core model and the structure to be solved must be less than 2 Å. Here, an approach originally implemented in the CaspR server (http://www.igs.cnrs-mrs.fr/Caspr2/index.cgi) based on homology modelling to search for a molecular-replacement solution is discussed. How the use of as much information as possible from different sources can improve the model(s) is briefly described. The combination of structural information with distantly related sequences is crucial to optimize the multiple alignment that will define the boundaries of the core domains. PDB clusters (sequences with ≥30% identical residues) can also provide information on the eventual changes in conformation and will help to explore the relative orientations assumed by protein subdomains. Normal-mode analysis can also help in generating series of conformational models in the search for a molecular-replacement solution. Of course, finding a correct solution is only the first step and the accuracy of the identified solution is as important as the data quality to proceed through refinement. Here, some possible reasons for failure are discussed and solutions are proposed using a set of successful examples.« less

Insights into geometries, stabilities, electronic structures, reactivity descriptors, and magnetic properties of bimetallic Nim Cun-m (m = 1, 2; n = 3-13) clusters: Comparison with pure copper clusters.

PubMed

Singh, Raman K; Iwasa, Takeshi; Taketsugu, Tetsuya

2018-05-25

A long-range corrected density functional theory (LC-DFT) was applied to study the geometric structures, relative stabilities, electronic structures, reactivity descriptors and magnetic properties of the bimetallic NiCu n -1 and Ni 2 Cu n -2 (n = 3-13) clusters, obtained by doping one or two Ni atoms to the lowest energy structures of Cu n , followed by geometry optimizations. The optimized geometries revealed that the lowest energy structures of the NiCu n -1 and Ni 2 Cu n -2 clusters favor the Ni atom(s) situated at the most highly coordinated position of the host copper clusters. The averaged binding energy, the fragmentation energies and the second-order energy differences signified that the Ni doped clusters can continue to gain an energy during the growth process. The electronic structures revealed that the highest occupied molecular orbital and the lowest unoccupied molecular orbital energies of the LC-DFT are reliable and can be used to predict the vertical ionization potential and the vertical electron affinity of the systems. The reactivity descriptors such as the chemical potential, chemical hardness and electrophilic power, and the reactivity principle such as the minimum polarizability principle are operative for characterizing and rationalizing the electronic structures of these clusters. Moreover, doping of Ni atoms into the copper clusters carry most of the total spin magnetic moment. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Constraint Logic Programming approach to protein structure prediction.

PubMed

Dal Palù, Alessandro; Dovier, Agostino; Fogolari, Federico

2004-11-30

The protein structure prediction problem is one of the most challenging problems in biological sciences. Many approaches have been proposed using database information and/or simplified protein models. The protein structure prediction problem can be cast in the form of an optimization problem. Notwithstanding its importance, the problem has very seldom been tackled by Constraint Logic Programming, a declarative programming paradigm suitable for solving combinatorial optimization problems. Constraint Logic Programming techniques have been applied to the protein structure prediction problem on the face-centered cube lattice model. Molecular dynamics techniques, endowed with the notion of constraint, have been also exploited. Even using a very simplified model, Constraint Logic Programming on the face-centered cube lattice model allowed us to obtain acceptable results for a few small proteins. As a test implementation their (known) secondary structure and the presence of disulfide bridges are used as constraints. Simplified structures obtained in this way have been converted to all atom models with plausible structure. Results have been compared with a similar approach using a well-established technique as molecular dynamics. The results obtained on small proteins show that Constraint Logic Programming techniques can be employed for studying protein simplified models, which can be converted into realistic all atom models. The advantage of Constraint Logic Programming over other, much more explored, methodologies, resides in the rapid software prototyping, in the easy way of encoding heuristics, and in exploiting all the advances made in this research area, e.g. in constraint propagation and its use for pruning the huge search space.

Optimization of the molecular dynamics method for simulations of DNA and ion transport through biological nanopores.

PubMed

Wells, David B; Bhattacharya, Swati; Carr, Rogan; Maffeo, Christopher; Ho, Anthony; Comer, Jeffrey; Aksimentiev, Aleksei

2012-01-01

Molecular dynamics (MD) simulations have become a standard method for the rational design and interpretation of experimental studies of DNA translocation through nanopores. The MD method, however, offers a multitude of algorithms, parameters, and other protocol choices that can affect the accuracy of the resulting data as well as computational efficiency. In this chapter, we examine the most popular choices offered by the MD method, seeking an optimal set of parameters that enable the most computationally efficient and accurate simulations of DNA and ion transport through biological nanopores. In particular, we examine the influence of short-range cutoff, integration timestep and force field parameters on the temperature and concentration dependence of bulk ion conductivity, ion pairing, ion solvation energy, DNA structure, DNA-ion interactions, and the ionic current through a nanopore.

A COMPUTER MODELING STUDY OF BINDING PROPERTIES OF CHIRAL NUCLEOPEPTIDE FOR BIOMEDICAL APPLICATIONS.

PubMed

Pirtskhalava, M; Egoyan, A; Mirtskhulava, M; Roviello, G

2017-12-01

Nucleopeptides often show interesting properties of molecular binding that render them good candidates for development of innovative drugs for anticancer and antiviral therapies. In this work we present results of computer modeling of interactions between the molecules of hexathymine nucleopeptide (T6) and poly rA RNA (A18). The results of geometry optimization calculated using Hyperchem software and our own computer program for molecular docking show that molecules establish stable complexes due to the complementary-nucleobase interaction and the electrostatic interaction between the negative phosphate group of poly rA and the positively-charged residues present in the cationic nucleopeptide structure. Computer modeling makes it possible to find the optimal binding configuration of the molecules of a nucleopeptide and poly rA RNA and to estimate the binding energy between the molecules.

Conformational analysis of α-helical polypeptide included L-proline residue by high-resolution solid-state NMR measurement and quantum chemical calculation

NASA Astrophysics Data System (ADS)

Souma, Hiroyuki; Shoji, Akira; Kurosu, Hiromichi

2008-10-01

We challenged the problem about the stabilization mechanism of an α-helix formation for polypeptides containing L-proline (Pro) residue. We computed the optimized structure of α-helical poly( L-alanine) molecules including a Pro residue, H-(Ala) 8-Pro-(Ala) 9-OH, based on the molecular orbital calculation with density functional theory, B3LYP/6-31G(d) and the 13C and 15N chemical shift values based on the GIAO-CHF method with B3LYP/6-311G(d,p), respectively. It was found that two kinds of optimized structures, 'Bent structure' and 'Included α-helix structure', were preferred structures in H-(Ala) 8-Pro-(Ala) 9-OH. In addition, based on the precise 13C and 15N chemical shift data of the simple model, we successfully analyzed the secondary structure of well-defined synthetic polypeptide H-(Phe-Leu-Ala) 3-Phe C-Pro-Ala N-(Phe-Leu-Ala) 2-OH (FLA-11P), the secondary structure of which was proven to the 'Included α-helix structure'.

Use of an auxiliary basis set to describe the polarization in the fragment molecular orbital method

NASA Astrophysics Data System (ADS)

Fedorov, Dmitri G.; Kitaura, Kazuo

2014-03-01

We developed a dual basis approach within the fragment molecular orbital formalism enabling efficient and accurate use of large basis sets. The method was tested on water clusters and polypeptides and applied to perform geometry optimization of chignolin (PDB: 1UAO) in solution at the level of DFT/6-31++G∗∗, obtaining a structure in agreement with experiment (RMSD of 0.4526 Å). The polarization in polypeptides is discussed with a comparison of the α-helix and β-strand.

ATOMIC RESOLUTION CRYO ELECTRON MICROSCOPY OF MACROMOLECULAR COMPLEXES

PubMed Central

ZHOU, Z. HONG

2013-01-01

Single-particle cryo electron microscopy (cryoEM) is a technique for determining three-dimensional (3D) structures from projection images of molecular complexes preserved in their “native,” noncrystalline state. Recently, atomic or near-atomic resolution structures of several viruses and protein assemblies have been determined by single-particle cryoEM, allowing ab initio atomic model building by following the amino acid side chains or nucleic acid bases identifiable in their cryoEM density maps. In particular, these cryoEM structures have revealed extended arms contributing to molecular interactions that are otherwise not resolved by the conventional structural method of X-ray crystallography at similar resolutions. High-resolution cryoEM requires careful consideration of a number of factors, including proper sample preparation to ensure structural homogeneity, optimal configuration of electron imaging conditions to record high-resolution cryoEM images, accurate determination of image parameters to correct image distortions, efficient refinement and computation to reconstruct a 3D density map, and finally appropriate choice of modeling tools to construct atomic models for functional interpretation. This progress illustrates the power of cryoEM and ushers it into the arsenal of structural biology, alongside conventional techniques of X-ray crystallography and NMR, as a major tool (and sometimes the preferred one) for the studies of molecular interactions in supramolecular assemblies or machines. PMID:21501817

Conformational analysis of an acyclic tetrapeptide: ab-initio structure determination from X-ray powder diffraction, Hirshfeld surface analysis and electronic structure.

PubMed

Das, Uday; Naskar, Jishu; Mukherjee, Alok Kumar

2015-12-01

A terminally protected acyclic tetrapeptide has been synthesized, and the crystal structure of its hydrated form, Boc-Tyr-Aib-Tyr-Ile-OMe·2H2O (1), has been determined directly from powder X-ray diffraction data. The backbone conformation of tetrapeptide (1) exhibiting two consecutive β-turns is stabilized by two 4 → 1 intramolecular N-H · · · O hydrogen bonds. In the crystalline state, the tetrapeptide molecules are assembled through water-mediated O-H · · · O hydrogen bonds to form two-dimensional molecular sheets, which are further linked by intermolecular C-H · · · O hydrogen bonds into a three-dimensional supramolecular framework. The molecular electrostatic potential (MEP) surface of (1) has been used to supplement the crystallographic observations. The nature of intermolecular interactions in (1) has been analyzed quantitatively through the Hirshfeld surface and two-dimensional fingerprint plot. The DFT optimized molecular geometry of (1) agrees closely with that obtained from the X-ray structure analysis. The present structure analysis of Boc-Tyr-Aib-Tyr-Ile-OMe·2H2 O (1) represents a case where ab-initio crystal structure of an acyclic tetrapeptide with considerable molecular flexibility has been accomplished from laboratory X-ray powder diffraction data. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Complex formation and vectorization of a phosphorothioate oligonucleotide with an amphipathic leucine- and lysine-rich peptide: study at molecular and cellular levels.

PubMed

Boukhalfa-Heniche, Fatima-Zohra; Hernández, Belén; Gaillard, Stéphane; Coïc, Yves-Marie; Huynh-Dinh, Tam; Lecouvey, Marc; Seksek, Olivier; Ghomi, Mahmoud

2004-04-15

Optical spectroscopic techniques such as CD, Raman scattering, and fluorescence imaging allowed us to analyze the complex formation and vectorization of a single-stranded 20-mer phosphorothioate oligodeoxynucleotide with a 15-mer amphipathic peptide at molecular and cellular levels. Different solvent mixtures (methanol and water) and molecular ratios of peptide/oligodeoxynucleotide complexes were tested in order to overcome the problems related to solubility. Optimal conditions for both spectroscopic and cellular experiments were obtained with the molecular ratio peptide/oligodeoxynucleotide equal to 21:4, corresponding to a 7:5 ratio for their respective +/- charge ratio. At the molecular level, CD and Raman spectra were consistent with a alpha-helix conformation of the peptide in water or in a methanol-water mixture. The presence of methanol increased considerably the solubility of the peptide without altering its alpha-helix conformation, as evidenced by CD and Raman spectroscopies. UV absorption melting profile of the oligodeoxynucleotide gave rise to a flat melting profile, corresponding to its random structure in solution. Raman spectra of oligodeoxynucleotide/peptide complexes could only be studied in methanol/water mixture solutions. Drastic changes observed in Raman spectra have undoubtedly shown: (a) the perturbation occurred in the peptide secondary structure, and (b) possible interaction between the lysine residues of the peptide and the oligodeoxynucleotide. At the cellular level, the complex was prepared in a mixture of 10% methanol and 90% cell medium. Cellular uptake in optimal conditions for the oligodeoxynucleotide delivery with low cytotoxicity was controlled by fluorescence imaging allowing to specifically locate the compacted oligonucleotide labeled with fluorescein at its 5'-terminus with the peptide into human glioma cells after 1 h of incubation at 37 degrees C. Copyright 2004 Wiley Periodicals, Inc.

Computational Investigation of the pH Dependence of Loop Flexibility and Catalytic Function in Glycoside Hydrolases*

PubMed Central

Bu, Lintao; Crowley, Michael F.; Himmel, Michael E.; Beckham, Gregg T.

2013-01-01

Cellulase enzymes cleave glycosidic bonds in cellulose to produce cellobiose via either retaining or inverting hydrolysis mechanisms, which are significantly pH-dependent. Many fungal cellulases function optimally at pH ∼5, and their activities decrease dramatically at higher or lower pH. To understand the molecular-level implications of pH in cellulase structure, we use a hybrid, solvent-based, constant pH molecular dynamics method combined with pH-based replica exchange to determine the pKa values of titratable residues of a glycoside hydrolase (GH) family 6 cellobiohydrolase (Cel6A) and a GH family 7 cellobiohydrolase (Cel7A) from the fungus Hypocrea jecorina. For both enzymes, we demonstrate that a bound substrate significantly affects the pKa values of the acid residues at the catalytic center. The calculated pKa values of catalytic residues confirm their proposed roles from structural studies and are consistent with the experimentally measured apparent pKa values. Additionally, GHs are known to impart a strained pucker conformation in carbohydrate substrates in active sites for catalysis, and results from free energy calculations combined with constant pH molecular dynamics suggest that the correct ring pucker is stable near the optimal pH for both Cel6A and Cel7A. Much longer molecular dynamics simulations of Cel6A and Cel7A with fixed protonation states based on the calculated pKa values suggest that pH affects the flexibility of tunnel loops, which likely affects processivity and substrate complexation. Taken together, this work demonstrates several molecular-level effects of pH on GH enzymes important for cellulose turnover in the biosphere and relevant to biomass conversion processes. PMID:23504310

Modular Homogeneous Chromophore–Catalyst Assemblies

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

Mulfort, Karen L.; Utschig, Lisa M.

2016-05-17

Photosynthetic reaction center (RC) proteins convert incident solar energy to chemical energy through a network of molecular cofactors which have been evolutionarily tuned to couple efficient light-harvesting, directional electron transfer, and long-lived charge separation with secondary reaction sequences. These molecular cofactors are embedded within a complex protein environment which precisely positions each cofactor in optimal geometries along efficient electron transfer pathways with localized protein environments facilitating sequential and accumulative charge transfer. By contrast, it is difficult to approach a similar level of structural complexity in synthetic architectures for solar energy conversion. However, by using appropriate self-assembly strategies, we anticipate thatmore » molecular modules, which are independently synthesized and optimized for either light-harvesting or redox catalysis, can be organized into spatial arrangements that functionally mimic natural photosynthesis. In this Account, we describe a modular approach to new structural designs for artificial photosynthesis which is largely inspired by photosynthetic RC proteins. We focus on recent work from our lab which uses molecular modules for light-harvesting or proton reduction catalysis in different coordination geometries and different platforms, spanning from discrete supramolecular assemblies to molecule–nanoparticle hybrids to protein-based biohybrids. Molecular modules are particularly amenable to high-resolution characterization of the ground and excited state of each module using a variety of physical techniques; such spectroscopic interrogation helps our understanding of primary artificial photosynthetic mechanisms. In particular, we discuss the use of transient optical spectroscopy, EPR, and X-ray scattering techniques to elucidate dynamic structural behavior and light-induced kinetics and the impact on photocatalytic mechanism. Two different coordination geometries of supramolecular photocatalyst based on the [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine) light-harvesting module with cobaloxime-based catalyst module are compared, with progress in stabilizing photoinduced charge separation identified. These same modules embedded in the small electron transfer protein ferredoxin exhibit much longer charge-separation, enabled by stepwise electron transfer through the native [2Fe-2S] cofactor. We anticipate that the use of interchangeable, molecular modules which can interact in different coordination geometries or within entirely different structural platforms will provide important fundamental insights into the effect of environment on parameters such as electron transfer and charge separation, and ultimately drive more efficient designs for artificial photosynthesis.« less

Specificity in the interaction of natural products with their target proteins--a biochemical and structural insight.

PubMed

Venkatraman, Prasanna

2010-06-01

Natural products are an abundant source of anti cancer agents. They act as cytotoxic drugs, and inhibitors of apoptosis, transcription, cell proliferation and angiogenesis. While pathways targeted by natural products have been well studied, there is paucity of information about the in vivo molecular target/s of these compounds. This review summarizes some of the natural compounds for which the molecular targets, mechanism of action and structural basis of specificity have been well documented. These examples illustrate that 'off target' binding can be explained on the basis of diversity inherent to biomolecular interactions. There is enough evidence to suggest that natural compounds are potent and versatile warheads that can be optimized for a multi targeted therapeutic intervention in cancer.

The Global Optimization of Pt13 Cluster Using the First-Principle Molecular Dynamics with the Quenching Technique

NASA Astrophysics Data System (ADS)

Chen, Xiangping; Duan, Haiming; Cao, Biaobing; Long, Mengqiu

2018-03-01

The high-temperature first-principle molecular dynamics method used to obtain the low energy configurations of clusters [L. L. Wang and D. D. Johnson, PRB 75, 235405 (2007)] is extended to a considerably large temperature range by combination with the quenching technique. Our results show that there are strong correlations between the possibilities for obtaining the ground-state structure and the temperatures. Larger possibilities can be obtained at relatively low temperatures (as corresponds to the pre-melting temperature range). Details of the structural correlation with the temperature are investigated by taking the Pt13 cluster as an example, which suggests a quite efficient method to obtain the lowest-energy geometries of metal clusters.

Theoretical calculations of Electron Paramagnetic Resonance parameters of liquid phase Orotic acid radical

NASA Astrophysics Data System (ADS)

Sarikaya, Ebru Karakaş; Dereli, Ömer

2017-02-01

To obtain liquid phase molecular structure, conformational analysis of Orotic acid was performed and six conformers were determined. For these conformations, eight possible radicals were modelled by using Density Functional Theory computations with respect to molecular structure. Electron Paramagnetic Resonance parameters of these model radicals were calculated and then they were compared with the experimental ones. Geometry optimizations of the molecule and modeled radicals were performed using Becke's three-parameter hybrid-exchange functional combined with the Lee-Yang-Parr correlation functional of Density Functional Theory and 6-311++G(d,p) basis sets in p-dioxane solution. Because Orotic acid can be mutagenic in mammalian somatic cells and it is also mutagenic for bacteria and yeast, it has been studied.

Computational Optimization and Characterization of Molecularly Imprinted Polymers

NASA Astrophysics Data System (ADS)

Terracina, Jacob J.

Molecularly imprinted polymers (MIPs) are a class of materials containing sites capable of selectively binding to the imprinted target molecule. Computational chemistry techniques were used to study the effect of different fabrication parameters (the monomer-to-target ratios, pre-polymerization solvent, temperature, and pH) on the formation of the MIP binding sites. Imprinted binding sites were built in silico for the purposes of better characterizing the receptor - ligand interactions. Chiefly, the sites were characterized with respect to their selectivities and the heterogeneity between sites. First, a series of two-step molecular mechanics (MM) and quantum mechanics (QM) computational optimizations of monomer -- target systems was used to determine optimal monomer-to-target ratios for the MIPs. Imidazole- and xanthine-derived target molecules were studied. The investigation included both small-scale models (one-target) and larger scale models (five-targets). The optimal ratios differed between the small and larger scales. For the larger models containing multiple targets, binding-site surface area analysis was used to evaluate the heterogeneity of the sites. The more fully surrounded sites had greater binding energies. Molecular docking was then used to measure the selectivities of the QM-optimized binding sites by comparing the binding energies of the imprinted target to that of a structural analogue. Selectivity was also shown to improve as binding sites become more fully encased by the monomers. For internal sites, docking consistently showed selectivity favoring the molecules that had been imprinted via QM geometry optimizations. The computationally imprinted sites were shown to exhibit size-, shape-, and polarity-based selectivity. This represented a novel approach to investigate the selectivity and heterogeneity of imprinted polymer binding sites, by applying the rapid orientation screening of MM docking to the highly accurate QM-optimized geometries. Next, we sought to computationally construct and investigate binding sites for their enantioselectivity. Again, a two-step MM [special characters removed] QM optimization scheme was used to "computationally imprint" chiral molecules. Using docking techniques, the imprinted binding sites were shown to exhibit an enantioselective preference for the imprinted molecule over its enantiomer. Docking of structurally similar chiral molecules showed that the sites computationally imprinted with R- or S-tBOC-tyrosine were able to differentiate between R- and S-forms of other tyrosine derivatives. The cross-enantioselectivity did not hold for chiral molecules that did not share the tyrosine H-bonding functional group orientations. Further analysis of the individual monomer - target interactions within the binding site led us to conclude that H-bonding functional groups that are located immediately next to the target's chiral center, and therefore spatially fixed relative to the chiral center, will have a stronger contribution to the enantioselectivity of the site than those groups separated from the chiral center by two or more rotatable bonds. These models were the first computationally imprinted binding sites to exhibit this enantioselective preference for the imprinted target molecules. Finally, molecular dynamics (MD) was used to quantify H-bonding interactions between target molecules, monomers, and solvents representative of the pre-polymerization matrix. It was found that both target dimerization and solvent interference decrease the number of monomer - target H-bonds present. Systems were optimized via simulated annealing to create binding sites that were then subjected to molecular docking analysis. Docking showed that the presence of solvent had a detrimental effect on the sensitivity and selectivity of the sites, and that solvents with more H-bonding capabilities were more disruptive to the binding properties of the site. Dynamic simulations also showed that increasing the temperature of the solution can significantly decrease the number of H-bonds formed between the targets and monomers. It is believed that the monomer - target complexes formed within the pre-polymerization matrix are translated into the selective binding cavities formed during polymerization. Elucidating the nature of these interactions in silico improves our understanding of MIPs, ultimately allowing for more optimized sensing materials.

Studies on N-picolinoyl-N‧-benzothioylhydrazide and its Zn(II) complex: Synthesis, structure, antibacterial activity, thermal analysis and DFT calculation

NASA Astrophysics Data System (ADS)

Kushawaha, S. K.; Dani, R. K.; Bharty, M. K.; Chaudhari, U. K.; Sharma, V. K.; Kharwar, R. N.; Singh, N. K.

2014-04-01

A new Zn(II) complex [Zn(pbth)2] (where Hpbth = N-picolinoyl-N‧-benzothioylhydrazide) has been synthesized and characterized by elemental analyses, IR, UV-Visible and single crystal X-ray data. The distorted octahedral complex [Zn(pbth)2] crystallizes in monoclinic system with space group C2/c and is stabilized by various types of inter and intramolecular extended hydrogen bonding providing supramolecular framework. The optimized molecular geometry of N-picolinoyl-N‧-benzothioylhydrazide (Hpbth) and the zinc complex in the ground state have been calculated by using the DFT method using B3LYP functional with 6-311 G(d,p){C,H,N,O,S}/Lanl2DZ basis set. The results of the optimized molecular geometry are presented and compared with the experimental X-ray diffraction data. In addition, quantum chemical calculations of Hpbth and the complex, molecular electrostatic potential (MEP), contour map and frontier molecular orbital analysis were performed. The solid state electrical conductivity and thermal behaviour (TGA) of the complex were investigated. The bioefficacy of the complex has been examined against the growth of bacteria in vitro to evaluate its anti-microbial potential.

From Geometry Optimization to Time Dependent Molecular Structure Modeling: Method Developments, ab initio Theories and Applications

NASA Astrophysics Data System (ADS)

Liang, Wenkel

This dissertation consists of two general parts: (I) developments of optimization algorithms (both nuclear and electronic degrees of freedom) for time-independent molecules and (II) novel methods, first-principle theories and applications in time dependent molecular structure modeling. In the first part, we discuss in specific two new algorithms for static geometry optimization, the eigenspace update (ESU) method in nonredundant internal coordinate that exhibits an enhanced performace with up to a factor of 3 savings in computational cost for large-sized molecular systems; the Car-Parrinello density matrix search (CP-DMS) method that enables direct minimization of the SCF energy as an effective alternative to conventional diagonalization approach. For the second part, we consider the time dependence and first presents two nonadiabatic dynamic studies that model laser controlled molecular photo-dissociation for qualitative understandings of intense laser-molecule interaction, using ab initio direct Ehrenfest dynamics scheme implemented with real-time time-dependent density functional theory (RT-TDDFT) approach developed in our group. Furthermore, we place our special interest on the nonadiabatic electronic dynamics in the ultrafast time scale, and presents (1) a novel technique that can not only obtain energies but also the electron densities of doubly excited states within a single determinant framework, by combining methods of CP-DMS with RT-TDDFT; (2) a solvated first-principles electronic dynamics method by incorporating the polarizable continuum solvation model (PCM) to RT-TDDFT, which is found to be very effective in describing the dynamical solvation effect in the charge transfer process and yields a consistent absorption spectrum in comparison to the conventional linear response results in solution. (3) applications of the PCM-RT-TDDFT method to study the intramolecular charge-transfer (CT) dynamics in a C60 derivative. Such work provides insights into the characteristics of ultrafast dynamics in photoexcited fullerene derivatives, and aids in the rational design for pre-dissociative exciton in the intramolecular CT process in organic solar cells.

Structural optimization of mangiferin binding to cancer molecular targets: a guide for synthetic derivatization.

PubMed

Taiwo, Bamigboye J; Olubiyi, Olujide O; van Heerden, Fanie R

2018-03-20

Nigerian medicinal plants have been demonstrated to be veritable source of lead compounds for drug discovery efforts. One such example is mangiferin. Mangiferin was originally isolated from the Nigerian plant Ceiba pentandra (Mombacaceae), after which its structure was elucidated with the aid of spectroscopy. Mangiferin, a xanthone glycoside, has also been reported in certain other plant families including Gentianaceae and Anacardiaceae. In certain other climes and different parts of the world, folkloric and traditional medicine has extensively employed Mangifera indica (another source of mangiferin) in treating different diseases. For many of such cultural uses carefully designed experimental investigations have been conducted confirming mangiferin's efficacies in those different pathologies which have included but not limited to cytotoxic as well as chemopreventive properties in selected cancer cell lines. In this study, computational techniques were employed to profile the interaction of the xanthone glycoside at the atomistic level against nine selected molecular targets with clinical relevance in tumorigenesis. In attempt to investigate the potential of the mangiferin structure as a viable starting point for synthetic exploration of mangiferin-based analogs, extensive structural modifications were performed. By analyzing the resulting structure-energetic pattern, critical points capable of improving mangiferin interaction with the profiled targets were identified. The outcome of this study provides both direction and impetus for synthetic derivitization of the mangiferin molecule into novel optimized inhibitors for anticancer lead development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A combined experimental and theoretical study of the supramolecular self-assembly of the natural benzopyran 2,2-dimethyl-3-hydroxy-6-acetyl-chromane and its isomeric benzofuran 10,11-dihydro-10-hydroxytremetone

NASA Astrophysics Data System (ADS)

Gil, Diego M.; Lizarraga, E.; Echeverría, G. A.; Piro, O. E.; Catalán, C. A. N.; Ben Altabef, A.

2017-10-01

Epoxidation of 4HMBA, the main metabolite of the medicinal plant Sencecionutans, produces an unstable epoxide eventually giving rise to a mixture of four derivatives, three of them previously reported as natural products. The epoxide product easily undergoes an intra-molecular attack of the phenolic hydroxyl against the epoxide group carbons to produce either a benzofuran or a chromane derivative. When dissolved in methanol-water mixture at room temperature the epoxide is completely solvolyzed to give the corresponding diol (hydrolysis) or vicinal hydroxyl-methoxy (methanolysis) derivative. All the compounds involved in the above reactions were characterized by IR, Raman, H NMR and UV-vis spectroscopies, and by mass spectrometry. Density functional theory (DFT) computations were used to optimize the structure conformations. The optimized structures were further subjected to a Natural Bond Orbital (NBO) and electrostatic potentials analysis. The crystal structures of the title compounds (for short, 3 and 4 respectively) were determined by X-ray diffraction methods. Compound 3 crystallizes in the triclinic P-1 space group with a = 6.4289 (6) Å, b = 8.7120 (6) Å, c = 10.952 (1) Å, α = 92.280 (7)°, β = 95.738 (7)°, γ = 103.973 (7)°, and Z = 2 molecules per unit cell and 4 in the monoclinic P21/c space group with a = 11.2891 (6) Å, b = 9.1902 (4) Å, c = 12.4272 (7) Å. Β = 113.689 (7)°, and Z = 4. In 3 neighboring molecules are linked to each other by OH⋯O (keto) bonds giving rise to a polymeric structure. In 4 the OH group is a bifurcate H-bond donor. It forms a weak intra-molecular OH⋯O (furan) bond and also a much stronger inter-molecular Osbnd H⋯O (keto) bond giving rise to a zig-zag polymeric structure. A detailed analysis of the solid state molecular interactions of compounds 3 and 4 has been performed using Hirshfeld surface analysis and their associated 2D fingerprint plots.

Chiral micellar electrokinetic chromatography-atmospheric pressure photoionization of benzoin derivatives using mixed molecular micelles.

PubMed

He, Jun; Shamsi, Shahab A

2011-05-01

In the present work we report, for the first time, the successful on-line coupling of chiral MEKC (CMEKC) to atmospheric pressure photoionization MS (APPI-MS). Four structurally similar neutral test solutes (e.g. benzoin (BNZ) derivatives) were successfully ionized by APPI-MS. The mass spectra in the positive ion mode showed that the protonated molecular ions of BNZs are not the most abundant fragment ions. Simultaneous enantioseparation by CMEKC and on-line APPI-MS detection of four photoinitiators, hydrobenzoin, BNZ, benzoin methyl ether, benzoin ethyl ether, were achieved using an optimized molar ratio of mixed molecular micelle of two polymeric chiral surfactants (polysodium N-undecenoxy carbonyl-L-leucinate and polysodium N-undecenoyl-L,L-leucylvalinate). The CMEKC conditions, such as voltage, chiral polymeric surfactant concentration, buffer pH, and BGE concentration, were optimized using a multivariate central composite design (CCD). The sheath liquid composition (involving %v/v methanol, dopant concentration, electrolyte additive concentration, and flow rate) and spray chamber parameters (drying gas flow rate, drying gas temperature, and vaporizer temperature) were also optimized with CCD. Models built based on the CCD results and response surface method were used to analyze the interactions between factors and their effects on the responses. The final overall optimum conditions for CMEKC-APPI-MS were also predicted and found in agreement with the experimentally optimized parameters. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectroscopic and molecular docking studies on the interaction of antiviral drug nevirapine with calf thymus DNA.

PubMed

Moghadam, Neda Hosseinpour; Salehzadeh, Sadegh; Shahabadi, Nahid

2017-09-02

The interaction of calf thymus DNA with nevirapine at physiological pH was studied by using absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, salt effect studies and computational methods. The drug binds to ct-DNA in a groove binding mode, as shown by slight variation in the viscosity of ct-DNA. Furthermore, competitive fluorimetric studies with Hoechst 33258 indicate that nevirapine binds to DNA via groove binding. Moreover, the structure of nevirapine was optimized by DFT calculations and was used for the molecular docking calculations. The molecular docking results suggested that nevirapine prefers to bind on the minor groove of ct-DNA.

Molecular structure, vibrational, electronic and thermal properties of 4-vinylcyclohexene by quantum chemical calculations

NASA Astrophysics Data System (ADS)

Nagabalasubramanian, P. B.; Periandy, S.; Karabacak, Mehmet; Govindarajan, M.

2015-06-01

The solid phase FT-IR and FT-Raman spectra of 4-vinylcyclohexene (abbreviated as 4-VCH) have been recorded in the region 4000-100 cm-1. The optimized molecular geometry and vibrational frequencies of the fundamental modes of 4-VCH have been precisely assigned and analyzed with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) method at 6-311++G(d,p) level basis set. The theoretical frequencies were properly scaled and compared with experimentally obtained FT-IR and FT-Raman spectra. Also, the effect due the substitution of vinyl group on the ring vibrational frequencies was analyzed and a detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated total energy distribution (TED). The time dependent DFT (TD-DFT) method was employed to predict its electronic properties, such as electronic transitions by UV-Visible analysis, HOMO and LUMO energies, molecular electrostatic potential (MEP) and various global reactivity and selectivity descriptors (chemical hardness, chemical potential, softness, electrophilicity index). Stability of the molecule arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Atomic charges obtained by Mulliken population analysis and NBO analysis are compared. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound at different temperatures are also calculated.

The VCD pattern of the ν(C=O) bands in isoindolinones.

PubMed

Rode, Joanna Ewa; Lyczko, Krzysztof; Jawiczuk, Magdalena; Kawęcki, Robert; Stańczyk, Wojciech; Jaglińska, Agnieszka; Dobrowolski, Jan Cz

2018-05-18

The IR and VCD spectra of both enantiomers of Me, iPr, nBu, Ph and CH2Ph substituted isoindolinones in solution and KBr pellets were measured and interpreted with DFT calculations. The spectra in solution revealed no important differences in the C=O stretching vibration region while the interpretation of very distinct spectra taken in pellets required determining the crystal structures. The studied compounds crystallized in the P212121 (Me, iPr, CH2Ph), P31 (nBu), and P21 (Ph) space groups. We found that the quality of simulated spectra strongly depends on the substituent, the structure of the molecular cluster assumed, basis set, and use of the dispersion correction. The IR spectra can be reproduced well based on the simplest linear arrangement of hydrogen-bonded chains mimicking the molecular arrangement in the crystals. We found no common approach to reproduce all the registered VCD spectra in the crystal phase. For the Me and nBu isoindolinones, the VCD pattern was the best reproduced by full optimization of the selected large molecular clusters. For iPr, Ph and CH2Ph derivatives optimizing only the position of H-atoms in a fragment frozen as in the crystal provides the best results. Such an approach can reduce the computation time from months to one week. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morse-Smale Analysis of Ion Diffusion in Ab Initio Battery Materials Simulations

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

Gyulassy, Attila; Knoll, Aaron; Lau, Kah Chun

Ab initio molecular dynamics (AIMD) simulations are increasingly useful in modeling, optimizing and synthesizing materials in energy sciences. In solving Schrödinger’s equation, they generate the electronic structure of the simulated atoms as a scalar field. However, methods for analyzing these volume data are not yet common in molecular visualization. The Morse-Smale complex is a proven, versatile tool for topological analysis of scalar fields. In this paper, we apply the discrete Morse-Smale complex to analysis of first-principles battery materials simulations. We consider a carbon nanosphere structure used in battery materials research, and employ Morse-Smale decomposition to determine the possible lithium ionmore » diffusion paths within that structure. Our approach is novel in that it uses the wavefunction itself as opposed distance fields, and that we analyze the 1-skeleton of the Morse-Smale complex to reconstruct our diffusion paths. Furthermore, it is the first application where specific motifs in the graph structure of the complete 1-skeleton define features, namely carbon rings with specific valence. We compare our analysis of DFT data with that of a distance field approximation, and discuss implications on larger classical molecular dynamics simulations.« less

Non-additivity of functional group contributions in protein-ligand binding: a comprehensive study by crystallography and isothermal titration calorimetry.

PubMed

Baum, Bernhard; Muley, Laveena; Smolinski, Michael; Heine, Andreas; Hangauer, David; Klebe, Gerhard

2010-04-09

Additivity of functional group contributions to protein-ligand binding is a very popular concept in medicinal chemistry as the basis of rational design and optimized lead structures. Most of the currently applied scoring functions for docking build on such additivity models. Even though the limitation of this concept is well known, case studies examining in detail why additivity fails at the molecular level are still very scarce. The present study shows, by use of crystal structure analysis and isothermal titration calorimetry for a congeneric series of thrombin inhibitors, that extensive cooperative effects between hydrophobic contacts and hydrogen bond formation are intimately coupled via dynamic properties of the formed complexes. The formation of optimal lipophilic contacts with the surface of the thrombin S3 pocket and the full desolvation of this pocket can conflict with the formation of an optimal hydrogen bond between ligand and protein. The mutual contributions of the competing interactions depend on the size of the ligand hydrophobic substituent and influence the residual mobility of ligand portions at the binding site. Analysis of the individual crystal structures and factorizing the free energy into enthalpy and entropy demonstrates that binding affinity of the ligands results from a mixture of enthalpic contributions from hydrogen bonding and hydrophobic contacts, and entropic considerations involving an increasing loss of residual mobility of the bound ligands. This complex picture of mutually competing and partially compensating enthalpic and entropic effects determines the non-additivity of free energy contributions to ligand binding at the molecular level. (c) 2010 Elsevier Ltd. All rights reserved.

Molecular structure, spectral studies, NBO, HOMO-LUMO profile, MEP and Mulliken analysis of 3β,6β-dichloro-5α-hydroxy-5α-cholestane

NASA Astrophysics Data System (ADS)

Alam, Mahboob; Park, Soonheum

2018-05-01

The synthesis of 3β,6β-dichloro-5α-hydroxy-5α-cholestane (in general, steroidal chlorohydrin or steroidal halohydrin) and theoretical study of the structure are reported in this paper. The individuality of chlorohydrin was confirmed by FT-IR, NMR, MS, CHN microanalysis and X-ray crystallography. DFT calculations on the titled molecule have been performed. The molecular structure and spectra explained by Gaussian hybrid computational analysis theory (B3LYP) are found to be in correlation with the experimental data obtained from the various spectrophotometric techniques. The theoretical geometry optimization data were compared with the X-ray data. The vibrational bands appearing in the FT-IR are assigned with accuracy using harmonic frequencies along with intensities and animated modes. Molecular properties like NBO, HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping and dipole moment have been dealt at same level of theory. The calculated electronic spectrum of chlorohydrin is interpreted on the basis of TD-DFT calculations.

Development of reactive force fields using ab initio molecular dynamics simulation minimally biased to experimental data

NASA Astrophysics Data System (ADS)

Chen, Chen; Arntsen, Christopher; Voth, Gregory A.

2017-10-01

Incorporation of quantum mechanical electronic structure data is necessary to properly capture the physics of many chemical processes. Proton hopping in water, which involves rearrangement of chemical and hydrogen bonds, is one such example of an inherently quantum mechanical process. Standard ab initio molecular dynamics (AIMD) methods, however, do not yet accurately predict the structure of water and are therefore less than optimal for developing force fields. We have instead utilized a recently developed method which minimally biases AIMD simulations to match limited experimental data to develop novel multiscale reactive molecular dynamics (MS-RMD) force fields by using relative entropy minimization. In this paper, we present two new MS-RMD models using such a parameterization: one which employs water with harmonic internal vibrations and another which uses anharmonic water. We show that the newly developed MS-RMD models very closely reproduce the solvation structure of the hydrated excess proton in the target AIMD data. We also find that the use of anharmonic water increases proton hopping, thereby increasing the proton diffusion constant.

Simulations of molecular self-assembled monolayers on surfaces: packing structures, formation processes and functions tuned by intermolecular and interfacial interactions.

PubMed

Wen, Jin; Li, Wei; Chen, Shuang; Ma, Jing

2016-08-17

Surfaces modified with a functional molecular monolayer are essential for the fabrication of nano-scale electronics or machines with novel physical, chemical, and/or biological properties. Theoretical simulation based on advanced quantum chemical and classical models is at present a necessary tool in the development, design, and understanding of the interfacial nanostructure. The nanoscale surface morphology, growth processes, and functions are controlled by not only the electronic structures (molecular energy levels, dipole moments, polarizabilities, and optical properties) of building units but also the subtle balance between intermolecular and interfacial interactions. The switchable surfaces are also constructed by introducing stimuli-responsive units like azobenzene derivatives. To bridge the gap between experiments and theoretical models, opportunities and challenges for future development of modelling of ferroelectricity, entropy, and chemical reactions of surface-supported monolayers are also addressed. Theoretical simulations will allow us to obtain important and detailed information about the structure and dynamics of monolayer modified interfaces, which will guide the rational design and optimization of dynamic interfaces to meet challenges of controlling optical, electrical, and biological functions.

Path integral molecular dynamic simulation of flexible molecular systems in their ground state: Application to the water dimer

NASA Astrophysics Data System (ADS)

Schmidt, Matthew; Roy, Pierre-Nicholas

2018-03-01

We extend the Langevin equation Path Integral Ground State (LePIGS), a ground state quantum molecular dynamics method, to simulate flexible molecular systems and calculate both energetic and structural properties. We test the approach with the H2O and D2O monomers and dimers. We systematically optimize all simulation parameters and use a unity trial wavefunction. We report ground state energies, dissociation energies, and structural properties using three different water models, two of which are empirically based, q-TIP4P/F and q-SPC/Fw, and one which is ab initio, MB-pol. We demonstrate that our energies calculated from LePIGS can be merged seamlessly with low temperature path integral molecular dynamics calculations and note the similarities between the two methods. We also benchmark our energies against previous diffusion Monte Carlo calculations using the same potentials and compare to experimental results. We further demonstrate that accurate vibrational energies of the H2O and D2O monomer can be calculated from imaginary time correlation functions generated from the LePIGS simulations using solely the unity trial wavefunction.

Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation

PubMed Central

Meduru, Harika; Wang, Yeng-Tseng; Tsai, Jeffrey J. P.; Chen, Yu-Ching

2016-01-01

Dipeptidyl peptidase-4 (DPP-4) is the vital enzyme that is responsible for inactivating intestinal peptides glucagon like peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), which stimulates a decline in blood glucose levels. The aim of this study was to explore the inhibition activity of small molecule inhibitors to DPP-4 following a computational strategy based on docking studies and molecular dynamics simulations. The thorough docking protocol we applied allowed us to derive good correlation parameters between the predicted binding affinities (pKi) of the DPP-4 inhibitors and the experimental activity values (pIC50). Based on molecular docking receptor-ligand interactions, pharmacophore generation was carried out in order to identify the binding modes of structurally diverse compounds in the receptor active site. Consideration of the permanence and flexibility of DPP-4 inhibitor complexes by means of molecular dynamics (MD) simulation specified that the inhibitors maintained the binding mode observed in the docking study. The present study helps generate new information for further structural optimization and can influence the development of new DPP-4 inhibitors discoveries in the treatment of type-2 diabetes. PMID:27304951

Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation.

PubMed

Meduru, Harika; Wang, Yeng-Tseng; Tsai, Jeffrey J P; Chen, Yu-Ching

2016-06-13

Dipeptidyl peptidase-4 (DPP-4) is the vital enzyme that is responsible for inactivating intestinal peptides glucagon like peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), which stimulates a decline in blood glucose levels. The aim of this study was to explore the inhibition activity of small molecule inhibitors to DPP-4 following a computational strategy based on docking studies and molecular dynamics simulations. The thorough docking protocol we applied allowed us to derive good correlation parameters between the predicted binding affinities (pKi) of the DPP-4 inhibitors and the experimental activity values (pIC50). Based on molecular docking receptor-ligand interactions, pharmacophore generation was carried out in order to identify the binding modes of structurally diverse compounds in the receptor active site. Consideration of the permanence and flexibility of DPP-4 inhibitor complexes by means of molecular dynamics (MD) simulation specified that the inhibitors maintained the binding mode observed in the docking study. The present study helps generate new information for further structural optimization and can influence the development of new DPP-4 inhibitors discoveries in the treatment of type-2 diabetes.

Molecular structure, vibrational spectra, NLO and MEP analysis of bis[2-hydroxy-кO-N-(2-pyridyl)-1-naphthaldiminato-кN]zinc(II)

NASA Astrophysics Data System (ADS)

Tanak, Hasan; Toy, Mehmet

2013-11-01

The molecular geometry and vibrational frequencies of bis[2-hydroxy-кO-N-(2-pyridyl)-1-naphthaldiminato-кN]zinc(II) in the ground state have been calculated by using the Hartree-Fock (HF) and density functional method (B3LYP) with 6-311G(d,p) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction. The energetic and atomic charge behavior of the title compound in solvent media has been examined by applying the Onsager and the polarizable continuum model. To investigate second order nonlinear optical properties of the title compound, the electric dipole (μ), linear polarizability (α) and first-order hyperpolarizability (β) were computed using the density functional B3LYP and CAM-B3LYP methods with the 6-31+G(d) basis set. According to our calculations, the title compound exhibits nonzero (β) value revealing second order NLO behavior. In addition, DFT calculations of the title compound, molecular electrostatic potential (MEP), frontier molecular orbitals, and thermodynamic properties were performed at B3LYP/6-311G(d,p) level of theory.

Electric Field Tuning Molecular Packing and Electrical Properties of Solution-Shearing Coated Organic Semiconducting Thin Films

DOE PAGES

Molina-Lopez, Francisco; Yan, Hongping; Gu, Xiaodan; ...

2017-01-17

Recent improvements in solution-coated organic semiconductors (OSCs) evidence their high potential for cost-efficient organic electronics and sensors. Molecular packing structure determines the charge transport property of molecular solids. However, it remains challenging to control the molecular packing structure for a given OSC. Here, the application of alternating electric fields is reported to fine-tune the crystal packing of OSC solution-shearing coated at ambient conditions. First, a theoretical model based on dielectrophoresis is developed to guide the selection of the optimal conditions (frequency and amplitude) of the electric field applied through the solution-shearing blade during coating of OSC thin films. Next, electricmore » field-induced polymorphism is demonstrated for OSCs with both herringbone and 2D brick-wall packing motifs in 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene and 6,13-bis(triisopropylsilylethynyl) pentacene, respectively. Favorable molecular packing can be accessible in some cases, resulting in higher charge carrier mobilities. In conclusion, this work provides a new approach to tune the properties of solution-coated OSCs in functional devices for high-performance printed electronics.« less

Imaging Molecular Motion: Femtosecond X-Ray Scattering of an Electrocyclic Chemical Reaction

NASA Astrophysics Data System (ADS)

Minitti, M. P.; Budarz, J. M.; Kirrander, A.; Robinson, J. S.; Ratner, D.; Lane, T. J.; Zhu, D.; Glownia, J. M.; Kozina, M.; Lemke, H. T.; Sikorski, M.; Feng, Y.; Nelson, S.; Saita, K.; Stankus, B.; Northey, T.; Hastings, J. B.; Weber, P. M.

2015-06-01

Structural rearrangements within single molecules occur on ultrafast time scales. Many aspects of molecular dynamics, such as the energy flow through excited states, have been studied using spectroscopic techniques, yet the goal to watch molecules evolve their geometrical structure in real time remains challenging. By mapping nuclear motions using femtosecond x-ray pulses, we have created real-space representations of the evolving dynamics during a well-known chemical reaction and show a series of time-sorted structural snapshots produced by ultrafast time-resolved hard x-ray scattering. A computational analysis optimally matches the series of scattering patterns produced by the x rays to a multitude of potential reaction paths. In so doing, we have made a critical step toward the goal of viewing chemical reactions on femtosecond time scales, opening a new direction in studies of ultrafast chemical reactions in the gas phase.

Imaging Molecular Motion: Femtosecond X-Ray Scattering of an Electrocyclic Chemical Reaction.

PubMed

Minitti, M P; Budarz, J M; Kirrander, A; Robinson, J S; Ratner, D; Lane, T J; Zhu, D; Glownia, J M; Kozina, M; Lemke, H T; Sikorski, M; Feng, Y; Nelson, S; Saita, K; Stankus, B; Northey, T; Hastings, J B; Weber, P M

2015-06-26

Structural rearrangements within single molecules occur on ultrafast time scales. Many aspects of molecular dynamics, such as the energy flow through excited states, have been studied using spectroscopic techniques, yet the goal to watch molecules evolve their geometrical structure in real time remains challenging. By mapping nuclear motions using femtosecond x-ray pulses, we have created real-space representations of the evolving dynamics during a well-known chemical reaction and show a series of time-sorted structural snapshots produced by ultrafast time-resolved hard x-ray scattering. A computational analysis optimally matches the series of scattering patterns produced by the x rays to a multitude of potential reaction paths. In so doing, we have made a critical step toward the goal of viewing chemical reactions on femtosecond time scales, opening a new direction in studies of ultrafast chemical reactions in the gas phase.

The atomic scale structure of CXV carbon: wide-angle x-ray scattering and modeling studies.

PubMed

Hawelek, L; Brodka, A; Dore, J C; Honkimaki, V; Burian, A

2013-11-13

The disordered structure of commercially available CXV activated carbon produced from finely powdered wood-based carbon has been studied using the wide-angle x-ray scattering technique, molecular dynamics and density functional theory simulations. The x-ray scattering data has been converted to the real space representation in the form of the pair correlation function via the Fourier transform. Geometry optimizations using classical molecular dynamics based on the reactive empirical bond order potential and density functional theory at the B3LYP/6-31g* level have been performed to generate nanoscale models of CXV carbon consistent with the experimental data. The final model of the structure comprises four chain-like and buckled graphitic layers containing a small percentage of four-fold coordinated atoms (sp(3) defects) in each layer. The presence of non-hexagonal rings in the atomic arrangement has been also considered.

Use of Molecular Dynamics for the Refinement of an Electrostatic Model for the In Silico Design of a Polymer Antidote for the Anticoagulant Fondaparinux

PubMed Central

Kwok, Ezra; Gopaluni, Bhushan; Kizhakkedathu, Jayachandran N.

2013-01-01

Molecular dynamics (MD) simulations results are herein incorporated into an electrostatic model used to determine the structure of an effective polymer-based antidote to the anticoagulant fondaparinux. In silico data for the polymer or its cationic binding groups has not, up to now, been available, and experimental data on the structure of the polymer-fondaparinux complex is extremely limited. Consequently, the task of optimizing the polymer structure is a daunting challenge. MD simulations provided a means to gain microscopic information on the interactions of the binding groups and fondaparinux that would have otherwise been inaccessible. This was used to refine the electrostatic model and improve the quantitative model predictions of binding affinity. Once refined, the model provided guidelines to improve electrostatic forces between candidate polymers and fondaparinux in order to increase association rate constants. PMID:27006916

Collection of X-ray diffraction data from macromolecular crystals

PubMed Central

Dauter, Zbigniew

2017-01-01

Diffraction data acquisition is the final experimental stage of the crystal structure analysis. All subsequent steps involve mainly computer calculations. Optimally measured and accurate data make the structure solution and refinement easier and lead to more faithful interpretation of the final models. Here, the important factors in data collection from macromolecular crystals are discussed and strategies appropriate for various applications, such as molecular replacement, anomalous phasing, atomic-resolution refinement etc., are presented. Criteria useful for judging the diffraction data quality are also discussed. PMID:28573573

Systematic Analysis of Polymer Molecular Weight Influence on the Organic Photovoltaic Performance.

PubMed

Katsouras, Athanasios; Gasparini, Nicola; Koulogiannis, Chrysanthos; Spanos, Michael; Ameri, Tayebeh; Brabec, Christoph J; Chochos, Christos L; Avgeropoulos, Apostolos

2015-10-01

The molecular weight of an electron donor-conjugated polymer is as essential as other well-known parameters in the chemical structure of the polymer, such as length and the nature of any side groups (alkyl chains) positioned on the polymeric backbone, as well as their placement, relative strength, the ratio of the donor and acceptor moieties in the backbone of donor-acceptor (D-A)-conjugated polymers, and the arrangement of their energy levels for organic photovoltaic performance. Finding the "optimal" molecular weight for a specific conjugated polymer is an important aspect for the development of novel photovoltaic polymers. Therefore, it is evident that the chemistry of functional conjugated polymers faces major challenges and materials have to adopt a broad range of specifications in order to be established for high photovoltaic performance. In this review, the approaches followed for enhancing the molecular weight of electron-donor polymers are presented in detail, as well as how this influences the optoelectronic properties, charge transport properties, structural conformation, morphology, and the photovoltaic performance of the active layer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surface stability and the selection rules of substrate orientation for optimal growth of epitaxial II-VI semiconductors

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

Yin, Wan-Jian; Department of Physics & Astronomy, and Wright Center for Photovoltaics Innovation and Commercialization, The University of Toledo, Toledo, Ohio 43606; Yang, Ji-Hui

2015-10-05

The surface structures of ionic zinc-blende CdTe (001), (110), (111), and (211) surfaces are systematically studied by first-principles density functional calculations. Based on the surface structures and surface energies, we identify the detrimental twinning appearing in molecular beam epitaxy (MBE) growth of II-VI compounds as the (111) lamellar twin boundaries. To avoid the appearance of twinning in MBE growth, we propose the following selection rules for choosing optimal substrate orientations: (1) the surface should be nonpolar so that there is no large surface reconstructions that could act as a nucleation center and promote the formation of twins; (2) the surfacemore » structure should have low symmetry so that there are no multiple equivalent directions for growth. These straightforward rules, in consistent with experimental observations, provide guidelines for selecting proper substrates for high-quality MBE growth of II-VI compounds.« less

Membrane-electrode structures for molecular catalysts for use in fuel cells and other electrochemical devices

DOEpatents

Kerr, John B.; Zhu, Xiaobing; Hwang, Gi Suk; Martin, Zulima; He, Qinggang; Driscoll, Peter; Weber, Adam; Clark, Kyle

2016-09-27

Water soluble catalysts, (M)meso-tetra(N-Methyl-4-Pyridyl)Porphinepentachloride (M=Fe, Co, Mn & Cu), have been incorporated into the polymer binder of oxygen reduction cathodes in membrane electrode assemblies used in PEM fuel cells and found to support encouragingly high current densities. The voltages achieved are low compared to commercial platinum catalysts but entirely consistent with the behavior observed in electroanalytical measurements of the homogeneous catalysts. A model of the dynamics of the electrode action has been developed and validated and this allows the MEA electrodes to be optimized for any chemistry that has been demonstrated in solution. It has been shown that improvements to the performance will come from modifications to the structure of the catalyst combined with optimization of the electrode structure and a well-founded pathway to practical non-platinum group metal catalysts exists.

Optimization of the random multilayer structure to break the random-alloy limit of thermal conductivity

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

Wang, Yan; Gu, Chongjie; Ruan, Xiulin, E-mail: ruan@purdue.edu

2015-02-16

A low lattice thermal conductivity (κ) is desired for thermoelectrics, and a highly anisotropic κ is essential for applications such as magnetic layers for heat-assisted magnetic recording, where a high cross-plane (perpendicular to layer) κ is needed to ensure fast writing while a low in-plane κ is required to avoid interaction between adjacent bits of data. In this work, we conduct molecular dynamics simulations to investigate the κ of superlattice (SL), random multilayer (RML) and alloy, and reveal that RML can have 1–2 orders of magnitude higher anisotropy in κ than SL and alloy. We systematically explore how the κmore » of SL, RML, and alloy changes relative to each other for different bond strength, interface roughness, atomic mass, and structure size, which provides guidance for choosing materials and structural parameters to build RMLs with optimal performance for specific applications.« less

Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2

NASA Astrophysics Data System (ADS)

Kalinić, Marko; Zloh, Mire; Erić, Slavica

2014-11-01

Enhancer of Zeste Homolog 2 (EZH2) is a SET domain protein lysine methyltransferase (PKMT) which has recently emerged as a chemically tractable and therapeutically promising epigenetic target, evidenced by the discovery and characterization of potent and highly selective EZH2 inhibitors. However, no experimental structures of the inhibitors co-crystallized to EZH2 have been resolved, and the structural basis for their activity and selectivity remains unknown. Considering the need to minimize cross-reactivity between prospective PKMT inhibitors, much can be learned from understanding the molecular basis for selective inhibition of EZH2. Thus, to elucidate the binding of small-molecule inhibitors to EZH2, we have developed a model of its fully-formed cofactor binding site and used it to carry out molecular dynamics simulations of protein-ligand complexes, followed by molecular mechanics/generalized born surface area calculations. The obtained results are in good agreement with biochemical inhibition data and reflect the structure-activity relationships of known ligands. Our findings suggest that the variable and flexible post-SET domain plays an important role in inhibitor binding, allowing possibly distinct binding modes of inhibitors with only small variations in their structure. Insights from this study present a good basis for design of novel and optimization of existing compounds targeting the cofactor binding site of EZH2.

Vibrational spectroscopic, structural and nonlinear optical activity studies on 6-aminonicotinamide: A DFT approach

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

Asath, R. Mohamed; Premkumar, S.; Mathavan, T.

2016-05-23

The conformational analysis was carried out for 6-aminonicotinamide (ANA) using potential energy surface scan method and the most stable optimized conformer was predicted. The theoretical vibrational frequencies were calculated for the optimized geometry using DFT/B3LYP cc-pVQZ basis set by Gaussian 09 Program. The vibrational frequencies were assigned on the basis of potential energy distribution calculation using VEDA 4.0 program. The Mulliken atomic charge values were calculated. In the Frontier molecular orbitals analysis, the molecular reactivity, kinetic stability, intermolecular charge transfer studies and the related molecular properties were calculated. The ultraviolet-visible spectrum was simulated for both in the gas phase andmore » liquid phase (ethanol) and the π to π* electronic transition was predicted. The nonlinear optical (NLO) activity was studied by means of the first order hyperpolarizability value, which was 8.61 times greater than the urea and the natural bond orbital analysis was also performed to confirm the NLO activity of the molecule. Hence, the ANA molecule is a promising candidate for the NLO materials.« less

Vibrational spectroscopic, structural and nonlinear optical activity studies on 6-aminonicotinamide: A DFT approach

NASA Astrophysics Data System (ADS)

Asath, R. Mohamed; Premkumar, S.; Rekha, T. N.; Jawahar, A.; Mathavan, T.; Benial, A. Milton Franklin

2016-05-01

The conformational analysis was carried out for 6-aminonicotinamide (ANA) using potential energy surface scan method and the most stable optimized conformer was predicted. The theoretical vibrational frequencies were calculated for the optimized geometry using DFT/B3LYP cc-pVQZ basis set by Gaussian 09 Program. The vibrational frequencies were assigned on the basis of potential energy distribution calculation using VEDA 4.0 program. The Mulliken atomic charge values were calculated. In the Frontier molecular orbitals analysis, the molecular reactivity, kinetic stability, intermolecular charge transfer studies and the related molecular properties were calculated. The ultraviolet-visible spectrum was simulated for both in the gas phase and liquid phase (ethanol) and the л to л* electronic transition was predicted. The nonlinear optical (NLO) activity was studied by means of the first order hyperpolarizability value, which was 8.61 times greater than the urea and the natural bond orbital analysis was also performed to confirm the NLO activity of the molecule. Hence, the ANA molecule is a promising candidate for the NLO materials.

Fully Anisotropic Rotational Diffusion Tensor from Molecular Dynamics Simulations.

PubMed

Linke, Max; Köfinger, Jürgen; Hummer, Gerhard

2018-05-31

We present a method to calculate the fully anisotropic rotational diffusion tensor from molecular dynamics simulations. Our approach is based on fitting the time-dependent covariance matrix of the quaternions that describe the rigid-body rotational dynamics. Explicit analytical expressions have been derived for the covariances by Favro, which are valid irrespective of the degree of anisotropy. We use these expressions to determine an optimal rotational diffusion tensor from trajectory data. The molecular structures are aligned against a reference by optimal rigid-body superposition. The quaternion covariances can then be obtained directly from the rotation matrices used in the alignment. The rotational diffusion tensor is determined by a fit to the time-dependent quaternion covariances, or directly by Laplace transformation and matrix diagonalization. To quantify uncertainties in the fit, we derive analytical expressions and compare them with the results of Brownian dynamics simulations of anisotropic rotational diffusion. We apply the method to microsecond long trajectories of the Dickerson-Drew B-DNA dodecamer and of horse heart myoglobin. The anisotropic rotational diffusion tensors calculated from simulations agree well with predictions from hydrodynamics.

Computer Based Porosity Design by Multi Phase Topology Optimization

NASA Astrophysics Data System (ADS)

Burblies, Andreas; Busse, Matthias

2008-02-01

A numerical simulation technique called Multi Phase Topology Optimization (MPTO) based on finite element method has been developed and refined by Fraunhofer IFAM during the last five years. MPTO is able to determine the optimum distribution of two or more different materials in components under thermal and mechanical loads. The objective of optimization is to minimize the component's elastic energy. Conventional topology optimization methods which simulate adaptive bone mineralization have got the disadvantage that there is a continuous change of mass by growth processes. MPTO keeps all initial material concentrations and uses methods adapted from molecular dynamics to find energy minimum. Applying MPTO to mechanically loaded components with a high number of different material densities, the optimization results show graded and sometimes anisotropic porosity distributions which are very similar to natural bone structures. Now it is possible to design the macro- and microstructure of a mechanical component in one step. Computer based porosity design structures can be manufactured by new Rapid Prototyping technologies. Fraunhofer IFAM has applied successfully 3D-Printing and Selective Laser Sintering methods in order to produce very stiff light weight components with graded porosities calculated by MPTO.

From Fullerene-Polymer to All-Polymer Solar Cells: The Importance of Molecular Packing, Orientation, and Morphology Control.

PubMed

Kang, Hyunbum; Lee, Wonho; Oh, Jiho; Kim, Taesu; Lee, Changyeon; Kim, Bumjoon J

2016-11-15

All-polymer solar cells (all-PSCs), consisting of conjugated polymers as both electron donor (P D ) and acceptor (P A ), have recently attracted great attention. Remarkable progress has been achieved during the past few years, with power conversion efficiencies (PCEs) now approaching 8%. In this Account, we first discuss the major advantages of all-PSCs over fullerene-polymer solar cells (fullerene-PSCs): (i) high light absorption and chemical tunability of P A , which affords simultaneous enhancement of both the short-circuit current density (J SC ) and the open-circuit voltage (V OC ), and (ii) superior long-term stability (in particular, thermal and mechanical stability) of all-PSCs due to entangled long P A chains. In the second part of this Account, we discuss the device operation mechanism of all-PSCs and recognize the major challenges that need to be addressed in optimizing the performance of all-PSCs. The major difference between all-PSCs and fullerene-PSCs originates from the molecular structures and interactions, i.e., the electron transport ability in all-PSCs is significantly affected by the packing geometry of two-dimensional P A chains relative to the electrodes (e.g., face-on or edge-on orientation), whereas spherically shaped fullerene acceptors can facilitate isotropic electron transport properties in fullerene-PSCs. Moreover, the crystalline packing structures of P D and P A at the P D -P A interface greatly affect their free charge carrier generation efficiencies. The design of P A polymers (e.g., main backbone, side chain, and molecular weight) should therefore take account of optimizing three major aspects in all-PSCs: (1) the electron transport ability of P A , (2) the molecular packing structure and orientation of P A , and (3) the blend morphology. First, control of the backbone and side-chain structures, as well as the molecular weight, is critical for generating strong intermolecular assembly of P A and its network, thus enabling high electron transport ability of P A comparable to that of fullerenes. Second, the molecular orientation of anisotropically structured P A should be favorably controlled in order to achieve efficient charge transport as well as charge transfer at the P D -P A interface. For instance, face-to-face stacking between P D and P A at the interface is desired for efficient free charge carrier generation because misoriented chains often cause an additional energy barrier for overcoming the binding energy of the charge transfer state. Third, large-scale phase separation often occurs in all-PSCs because of the significantly reduced entropic contribution by two macromolecular chains of P D and P A that energetically disfavors mixing. In this Account, we review the recent progress toward overcoming each recognized challenge and intend to provide guidelines for the future design of P A . We believe that by optimization of the parameters discussed above the PCE values of all-PSCs will surpass the 10% level in the near future and that all-PSCs are promising candidates for the successful realization of flexible and portable power generators.

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

Eaton, Craig; Brahlek, Matthew; Engel-Herbert, Roman, E-mail: rue2@psu.edu

The authors report the growth of stoichiometric SrVO{sub 3} thin films on (LaAlO{sub 3}){sub 0.3}(Sr{sub 2}AlTaO{sub 6}){sub 0.7} (001) substrates using hybrid molecular beam epitaxy. This growth approach employs a conventional effusion cell to supply elemental A-site Sr and the metalorganic precursor vanadium oxytriisopropoxide (VTIP) to supply vanadium. Oxygen is supplied in its molecular form through a gas inlet. An optimal VTIP:Sr flux ratio has been identified using reflection high-energy electron-diffraction, x-ray diffraction, atomic force microscopy, and scanning transmission electron microscopy, demonstrating stoichiometric SrVO{sub 3} films with atomically flat surface morphology. Away from the optimal VTIP:Sr flux, characteristic changes inmore » the crystalline structure and surface morphology of the films were found, enabling identification of the type of nonstoichiometry. For optimal VTIP:Sr flux ratios, high quality SrVO{sub 3} thin films were obtained with smallest deviation of the lattice parameter from the ideal value and with atomically smooth surfaces, indicative of the good cation stoichiometry achieved by this growth technique.« less

Development and optimization of the synthesis of new thiazolidin-4-one derivatives of ibuprofen.

PubMed

Vasincu, Ioana; Apotrosoaei, Maria; Panzariu, Andreea; Buron, F; Routier, S; Profire, Lenuta

2014-01-01

Ibuprofen, an important nonsteroidal anti-inflammatory agent, is one of the most prescribed drugs for the treatment of pain and inflammation from various rheumatic diseases, but some side effects can occur on long-term use. The method for synthesis optimization of new derivatives of Ibuprofen with thiazolidin-4-one moiety, with improved pharmacological and toxicological profile. To optimize the derivatization method of free carboxyl group of Ibuprofen (2-(4-isobutylphenyl)propionic acid) the reaction conditions were varied (reagent ratio, catalyst, reaction medium). The most favorable method was proved to be the reaction between ibuprofen hydrazone and mercaptoacetic acid, in excess, at 80-85 degrees C, for 6 h with 96% conversion rate. The synthesis of 2-phenyl-3-[2-(4-(isobutyl)phenyl)-2-methyl]acetamido-thiazolidin-4-one derivative was optimized in view of applying it as a general procedure for the synthesis of other derivatives with related structure. The chemical structure and molecular weight of the synthesized compound were confirmed by spectral methods (IR, 1H NMR, 13C NMR, HR-MS).

Enzymatically catalyzed synthesis of low-calorie structured lipid in a solvent-free system: optimization by response surface methodology.

PubMed

Han, Lu; Xu, Zijian; Huang, Jianhua; Meng, Zong; Liu, Yuanfa; Wang, Xingguo

2011-12-14

A kind of low-calorie structured lipid (LCSL) was obtained by interesterification of tributyrin (TB) and methyl stearate (St-ME), catalyzed by a commercially immobilized 1,3-specific lipase, Lipozyme RM IM from Rhizomucor miehei . The condition optimization of the process was conducted by using response surface methodology (RSM). The optimal conditions for highest conversion of St-ME and lowest content LLL-TAG (SSS and SSP; S, stearic acid; P, palmitic acid) were determined to be a reaction time 6.52 h, a substrate molar ratio (St-ME:TB) of 1.77:1, and an enzyme amount of 10.34% at a reaction temperature of 65 °C; under these conditions, the actually measured conversion of St-ME and content of LLL-TAG were 78.47 and 4.89% respectively, in good agreement with predicted values. The target product under optimal conditions after short-range molecular distillation showed solid fat content (SFC) values similar to those of cocoa butter substitutes (CBS), cocoa butter equivalent (CBE), and cocoa butters (CB), indicating its application for inclusion with other fats as cocoa butter substitutes.

Optimizing molecular properties using a relative index of thermodynamic stability and global optimization techniques

NASA Astrophysics Data System (ADS)

Fournier, René; Mohareb, Amir

2016-01-01

We devised a global optimization (GO) strategy for optimizing molecular properties with respect to both geometry and chemical composition. A relative index of thermodynamic stability (RITS) is introduced to allow meaningful energy comparisons between different chemical species. We use the RITS by itself, or in combination with another calculated property, to create an objective function F to be minimized. Including the RITS in the definition of F ensures that the solutions have some degree of thermodynamic stability. We illustrate how the GO strategy works with three test applications, with F calculated in the framework of Kohn-Sham Density Functional Theory (KS-DFT) with the Perdew-Burke-Ernzerhof exchange-correlation. First, we searched the composition and configuration space of CmHnNpOq (m = 0-4, n = 0-10, p = 0-2, q = 0-2, and 2 ≤ m + n + p + q ≤ 12) for stable molecules. The GO discovered familiar molecules like N2, CO2, acetic acid, acetonitrile, ethane, and many others, after a small number (5000) of KS-DFT energy evaluations. Second, we carried out a GO of the geometry of Cu m Snn + (m = 1, 2 and n = 9-12). A single GO run produced the same low-energy structures found in an earlier study where each Cu m S nn + species had been optimized separately. Finally, we searched bimetallic clusters AmBn (3 ≤ m + n ≤ 6, A,B= Li, Na, Al, Cu, Ag, In, Sn, Pb) for species and configurations having a low RITS and large highest occupied Molecular Orbital (MO) to lowest unoccupied MO energy gap (Eg). We found seven bimetallic clusters with Eg > 1.5 eV.

Role of Molecular Dynamics and Related Methods in Drug Discovery.

PubMed

De Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, Andrea

2016-05-12

Molecular dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theoretical background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water molecules in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.

Optimization of the Nonradiative Lifetime of Molecular-Beam-Epitaxy (MBE)-Grown Undoped GaAs/AlGaAs Double Heterostructures (DH)

DTIC Science & Technology

2013-09-01

Optimization of the Nonradiative Lifetime of Molecular- Beam-Epitaxy (MBE)-Grown Undoped GaAs/AlGaAs Double Heterostructures (DH) by P...it to the originator. Army Research Laboratory Adelphi, MD 20783-1197 ARL-TR-6660 September 2013 Optimization of the Nonradiative ...REPORT TYPE Final 3. DATES COVERED (From - To) FY2013 4. TITLE AND SUBTITLE Optimization of the Nonradiative Lifetime of Molecular-Beam-Epitaxy

Ultrasound effects on the degradation kinetics, structure, and antioxidant activity of sea cucumber fucoidan.

PubMed

Guo, Xin; Ye, Xingqian; Sun, Yujing; Wu, Dan; Wu, Nian; Hu, Yaqin; Chen, Shiguo

2014-02-05

The effects of ultrasound on the molecular weight, structure, and antioxidant potential of a fucoidan found in Isostichopus badionotus were investigated. The results showed the molecular weight (Mw) of fucoidan decreased obviously after ultrasound treatment. Higher ultrasonic intensity, lower temperature, and lower fucoidan concentrations led to a more effective sonochemical effect. The kinetic model for fucoidan degradation fitted to 1/M(wt)-1/M(w0) = kt at the tested temperature. The optimized degradation conditions by response surface methodology (RSM) were temperature, 12 °C, and intensity, 508 W/cm². Structural analysis by FTIR and NMR indicated the fucoidan kept the linear tetrasaccharide repeating units as the original polysaccharides after the ultrasound treatment, with only slight destruction of the middle nonsulfated fucose units. Antioxidant activity assay showed the antioxidant activity was slightly improved by the ultrasound treatment. The results suggested that ultrasound treatment is an effective approach to decrease the M(w) of fucoidan with only minor structural destruction.

The crystal structure of sulfamethoxazole, interaction with DNA, DFT calculation, and molecular docking studies

NASA Astrophysics Data System (ADS)

Das, Dipankar; Sahu, Nilima; Roy, Suman; Dutta, Paramita; Mondal, Sudipa; Torres, Elena L.; Sinha, Chittaranjan

2015-02-01

Sulfamethoxazole (SMX) [4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide] is structurally established by single crystal X-ray diffraction measurement. The crystal packing shows H-bonded 2D polymer through N(7)sbnd H(7A)---O(2), N(7)sbnd H(7B)---O(3), N(1)sbnd H(1)---N(2), C(5)sbnd H(5)---O(3)sbnd S(1) and N(7)sbnd (H7A)---O(2)sbnd S(1). Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) computations of optimized structure of SMX determine the electronic structure and has explained the electronic spectral transitions. The interaction of SMX with CT-DNA has been studied by absorption spectroscopy and the binding constant (Kb) is 4.37 × 104 M-1. The in silico test of SMX with DHPS from Escherichia coli and Streptococcus pneumoniae helps to understand drug metabolism and accounts the drug-molecule interactions. The molecular docking of SMX-DNA also helps to predict the interaction feature.

On the structure-bounded growth processes in plant populations.

PubMed

Kilian, H G; Kazda, M; Király, F; Kaufmann, D; Kemkemer, R; Bartkowiak, D

2010-07-01

If growing cells in plants are considered to be composed of increments (ICs) an extended version of the law of mass action can be formulated. It evidences that growth of plants runs optimal if the reaction-entropy term (entropy times the absolute temperature) matches the contact energy of ICs. Since these energies are small, thermal molecular movements facilitate via relaxation the removal of structure disturbances. Stem diameter distributions exhibit extra fluctuations likely to be caused by permanent constraints. Since the signal-response system enables in principle perfect optimization only within finite-sized cell ensembles, plants comprising relatively large cell numbers form a network of size-limited subsystems. The maximal number of these constituents depends both on genetic and environmental factors. Accounting for logistical structure-dynamics interrelations, equations can be formulated to describe the bimodal growth curves of very different plants. The reproduction of the S-bended growth curves verifies that the relaxation modes with a broad structure-controlled distribution freeze successively until finally growth is fully blocked thus bringing about "continuous solidification".

DG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screening.

PubMed

Lagorce, David; Pencheva, Tania; Villoutreix, Bruno O; Miteva, Maria A

2009-11-13

Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

Insight into the theoretical and experimental studies of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N(4)-methyl-N(4)- phenylthiosemicarbazone - A potential NLO material

NASA Astrophysics Data System (ADS)

Sangeetha, K. G.; Aravindakshan, K. K.; Safna Hussan, K. P.

2017-12-01

The synthesis, geometrical parameters, spectroscopic studies, optimised molecular structure, vibrational analysis, Mullikan population analysis, MEP, NBO, frontier molecular orbitals and NLO effects of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N-(4)-methyl-N-(4)-phenylthiosemicarbazone, C25H23N5OS (L1) have been communicated in this paper. A combined experimental and theoretical approach was used to explore the structure and properties of the compound. For computational studies, Gaussian 09 program was used. Starting geometry of molecule was taken from X-ray refinement data and has been optimized by using DFT (B3LYP) method with the 6-31+G (d, p) basis sets. NBO analysis gave insight into the strongly delocalized structure, responsible for the nonlinearity and hence the stability of the molecule. Frontier molecular orbitals have been defined to forecast the global reactivity descriptors of L1. The computed first-order hyperpolarizability (β) of the compound is 2 times higher than that of urea and this account for its nonlinear optical property. Simultaneously, a molecular docking study of the compound was performed using GLIDE Program. For this, three biological enzymes, histone deacetylase, ribonucleotide reductase and DNA methyl transferase, were selected as receptor molecules.

Syntheses, spectroscopic properties and molecular structure of silver phytate complexes - IR, UV-VIS studies and DFT calculations

NASA Astrophysics Data System (ADS)

Zając, A.; Dymińska, L.; Lorenc, J.; Ptak, M.; Hanuza, J.

2018-03-01

Silver phytate IP6, IP6Ag, IP6Ag2 and IP6Ag3 complexes in the solid state have been synthesized changing the phosphate to metal mole ratio. The obtained products have been characterized by means of chemical and spectroscopic studies. Attenuated total reflection Fourier transform infrared technique and Raman microscope were used in the measurements. These results were discussed in terms of DFT (Density Functional Theory) quantum chemical calculations using the B3LYP/6-31G(d,p) approach. The molecular structures of these compounds have been proposed on the basis of group theory and geometry optimization taking into account the shape and the number of the observed bands corresponding to the stretching and bending vibrations of the phosphate group and metal-oxygen polyhedron. The role of inter- and intra-hydrogen bonds in stabilization of the structure has been discussed. It was found that three types of hydrogen bonds appear in the studied compounds: terminal, and those engaged in the inter- and intra-molecular interactions. The Fermi resonance as a result of the strong intra-molecular Osbnd H⋯O hydrogen bonds was discovered. Electron absorption spectra have been measured to characterize the electron properties of the studied complexes and their local symmetry.

Novel hybrid structure silica/CdTe/molecularly imprinted polymer: synthesis, specific recognition, and quantitative fluorescence detection of bovine hemoglobin.

PubMed

Li, Dong-Yan; He, Xi-Wen; Chen, Yang; Li, Wen-You; Zhang, Yu-Kui

2013-12-11

This work presented a novel strategy for the synthesis of the hybrid structure silica/CdTe/molecularly imprinted polymer (Si-NP/CdTe/MIP) to recognize and detect the template bovine hemoglobin (BHb). First, amino-functionalized silica nanoparticles (Si-NP) and carboxyl-terminated CdTe quantum dots (QDs) were assembled into composite nanoparticles (Si-NP/CdTe) using the EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) chemistry. Next, Si-NP/CdTe/MIP was synthesized by anchoring molecularly imprinted polymer (MIP) layer on the surface of Si-NP/CdTe through the sol-gel technique and surface imprinting technique. The hybrid structure possessed the selectivity of molecular imprinting technique and the sensitivity of CdTe QDs as well as well-defined morphology. The binding experiment and fluorescence method demonstrated its special recognition performance toward the template BHb. Under the optimized conditions, the fluorescence intensity of the Si-NP/CdTe/MIP decreased linearly with the increase of BHb in the concentration range 0.02-2.1 μM, and the detection limit was 9.4 nM. Moreover, the reusability and reproducibility and the successful applications in practical samples indicated the synthesis of Si-NP/CdTe/MIP provided an alternative solution for special recognition and determination of protein from real samples.

Dipicolinate salt of imidazole: Discovering its structure and properties using different experimental methodologies and quantum chemical investigations

NASA Astrophysics Data System (ADS)

Thirumurugan, R.; Anitha, K.

2018-03-01

A novel organic proton transfer complex of imidazolium dipicolinate (ID) has been synthesized and it was grown as single crystals using slow evaporation method. The molecular structure of synthesized compound and vibrational modes of its functional groups were confirmed by (1H and 13C) NMR, FTIR and FT-Raman spectroscopic studies, respectively. Single crystal X-ray diffraction (SCXRD) analysis confirmed the orthorhombic system with noncentrosymmetric (NCS), P212121, space group of grown ID crystal. UV-Vis-NIR spectral study confirmed its high optical transparency within the region of 285-1500 nm. Powder second harmonic generation (SHG) efficiency of ID crystal was confirmed and it was 6.8 times that of KDP crystal. TG-DTA and DSC analysis revealed the higher thermal stability of grown crystal as 249 °C. The dielectric response and mechanical behaviour of grown crystal were studied effectively. Density functional theory calculations were performed to probe the relationship between the structure and its properties including molecular optimization, Mulliken atomic charge distribution, frontier molecular orbital (FMOs) and molecular electrostatic potential map (MEP) analysis and first hyperpolarizability. All these experimental and computational results were discussed in this communication and it endorsed the ID compound as a potential NLO candidate could be employed in optoelectronics device applications in near future.

Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets.

PubMed

Feinstein, Wei P; Brylinski, Michal

2015-01-01

Computational approaches have emerged as an instrumental methodology in modern research. For example, virtual screening by molecular docking is routinely used in computer-aided drug discovery. One of the critical parameters for ligand docking is the size of a search space used to identify low-energy binding poses of drug candidates. Currently available docking packages often come with a default protocol for calculating the box size, however, many of these procedures have not been systematically evaluated. In this study, we investigate how the docking accuracy of AutoDock Vina is affected by the selection of a search space. We propose a new procedure for calculating the optimal docking box size that maximizes the accuracy of binding pose prediction against a non-redundant and representative dataset of 3,659 protein-ligand complexes selected from the Protein Data Bank. Subsequently, we use the Directory of Useful Decoys, Enhanced to demonstrate that the optimized docking box size also yields an improved ranking in virtual screening. Binding pockets in both datasets are derived from the experimental complex structures and, additionally, predicted by eFindSite. A systematic analysis of ligand binding poses generated by AutoDock Vina shows that the highest accuracy is achieved when the dimensions of the search space are 2.9 times larger than the radius of gyration of a docking compound. Subsequent virtual screening benchmarks demonstrate that this optimized docking box size also improves compound ranking. For instance, using predicted ligand binding sites, the average enrichment factor calculated for the top 1 % (10 %) of the screening library is 8.20 (3.28) for the optimized protocol, compared to 7.67 (3.19) for the default procedure. Depending on the evaluation metric, the optimal docking box size gives better ranking in virtual screening for about two-thirds of target proteins. This fully automated procedure can be used to optimize docking protocols in order to improve the ranking accuracy in production virtual screening simulations. Importantly, the optimized search space systematically yields better results than the default method not only for experimental pockets, but also for those predicted from protein structures. A script for calculating the optimal docking box size is freely available at www.brylinski.org/content/docking-box-size. Graphical AbstractWe developed a procedure to optimize the box size in molecular docking calculations. Left panel shows the predicted binding pose of NADP (green sticks) compared to the experimental complex structure of human aldose reductase (blue sticks) using a default protocol. Right panel shows the docking accuracy using an optimized box size.

Post-natal molecular adaptations in anteromedial and posterolateral bundles of the ovine anterior cruciate ligament: one structure with two parts or two distinct ligaments?

PubMed

Huebner, Kyla D; O'Brien, Etienne J O; Heard, Bryan J; Chung, May; Achari, Yamini; Shrive, Nigel G; Frank, Cyril B

2012-01-01

The human anterior cruciate ligament (ACL) is a composite structure of two anatomically distinct bundles: an anteromedial (AM) and posterolateral (PL) bundles. Tendons are often used as autografts for surgical reconstruction of ACL following severe injury. However, despite successful surgical reconstruction, some people experience re-rupture and later development of osteoarthritis. Understanding the structure and molecular makeup of normal ACL is essential for its optimal replacement. Reportedly the two bundles display different tensions throughout joint motion and may be fundamentally different. This study assessed the similarities and differences in ultrastructure and molecular composition of the AM and PL bundles to test the hypothesis that the two bundles of the ACL develop unique characteristics with maturation. ACLs from nine mature and six immature sheep were compared. The bundles were examined for mRNA and protein levels of collagen types I, III, V, and VI, and two proteoglycans. The fibril diameter composition of the two bundles was examined with transmission electron microscopy. Maturation does alter the molecular and structural composition of the two bundles of ACL. Although the PL band appears to mature slower than the AM band, no significant differences were detected between the bundles in the mature animals. We thus reject our hypothesis that the two ACL bundles are distinct. The two anatomically distinct bundles of the sheep ACL can be considered as two parts of one structure at maturity and material that would result in a structure of similar functionality can be used to replace each ACL bundle in the sheep.

Novel ligands of Choline Acetyltransferase designed by in silico molecular docking, hologram QSAR and lead optimization

NASA Astrophysics Data System (ADS)

Kumar, Rajnish; Långström, Bengt; Darreh-Shori, Taher

2016-08-01

Recent reports have brought back the acetylcholine synthesizing enzyme, choline acetyltransferase in the mainstream research in dementia and the cholinergic anti-inflammatory pathway. Here we report, a specific strategy for the design of novel ChAT ligands based on molecular docking, Hologram Quantitative Structure Activity Relationship (HQSAR) and lead optimization. Molecular docking was performed on a series of ChAT inhibitors to decipher the molecular fingerprint of their interaction with the active site of ChAT. Then robust statistical fragment HQSAR models were developed. A library of novel ligands was generated based on the pharmacophoric and shape similarity scoring function, and evaluated in silico for their molecular interactions with ChAT. Ten of the top scoring invented compounds are reported here. We confirmed the activity of α-NETA, the only commercially available ChAT inhibitor, and one of the seed compounds in our model, using a new simple colorimetric ChAT assay (IC50 ~ 88 nM). In contrast, α-NETA exhibited an IC50 of ~30 μM for the ACh-degrading cholinesterases. In conclusion, the overall results may provide useful insight for discovering novel ChAT ligands and potential positron emission tomography tracers as in vivo functional biomarkers of the health of central cholinergic system in neurodegenerative disorders, such as Alzheimer’s disease.

Development of simulation approach for two-dimensional chiral molecular self-assembly driven by hydrogen bond at the liquid/solid interface

NASA Astrophysics Data System (ADS)

Qin, Yuan; Yao, Man; Hao, Ce; Wan, Lijun; Wang, Yunhe; Chen, Ting; Wang, Dong; Wang, Xudong; Chen, Yonggang

2017-09-01

Two-dimensional (2D) chiral self-assembly system of 5-(benzyloxy)-isophthalic acid derivative/(S)-(+)-2-octanol/highly oriented pyrolytic graphite was studied. A combined density functional theory/molecular mechanics/molecular dynamics (DFT/MM/MD) approach for system of 2D chiral molecular self-assembly driven by hydrogen bond at the liquid/solid interface was thus proposed. Structural models of the chiral assembly were built on the basis of scanning tunneling microscopy (STM) images and simplified for DFT geometry optimization. Merck Molecular Force Field (MMFF) was singled out as the suitable force field by comparing the optimized configurations of MM and DFT. MM and MD simulations for hexagonal unit model which better represented the 2D assemble network were then preformed with MMFF. The adhesion energy, evolution of self-assembly process and characteristic parameters of hydrogen bond were obtained and analyzed. According to the above simulation, the stabilities of the clockwise and counterclockwise enantiomorphous networks were evaluated. The calculational results were supported by STM observations and the feasibility of the simulation method was confirmed by two other systems in the presence of chiral co-absorbers (R)-(-)-2-octanol and achiral co-absorbers 1-octanol. This theoretical simulation method assesses the stability trend of 2D enantiomorphous assemblies with atomic scale and can be applied to the similar hydrogen bond driven 2D chirality of molecular self-assembly system.

Molecular dynamics of reversible self-healing materials

NASA Astrophysics Data System (ADS)

Madden, Ian; Luijten, Erik

Hydrolyzable polymers have numerous industrial applications as degradable materials. Recent experimental work by Cheng and co-workers has introduced the concept of hindered urea bond (HUB) chemistry to design self-healing systems. Important control parameters are the steric hindrance of the HUB structures, which is used to tune the hydrolytic degradation kinetics, and their density. We employ molecular dynamics simulations of polymeric interfaces to systematically explore the role of these properties in a coarse-grained model, and make direct comparison to experimental data. Our model provides direct insight into the self-healing process, permitting optimization of the control parameters.

Transformation characteristics of refractory pollutants in plugboard wastewater by an optimal electrocoagulation and electro-Fenton process.

PubMed

Zhao, Xu; Zhang, Baofeng; Liu, Huijuan; Chen, Fayuan; Li, Angzhen; Qu, Jiuhui

2012-05-01

The treatment of the plugboard wastewater was performed by an optimal electrocoagulation and electro-Fenton. The organic components with suspended fractions accounting for 30% COD were preferably removed via electrocoagulation at initial 5 min. In contrast, the removal efficiency was increased to 76% with the addition of H(2)O(2). The electrogenerated Fe(2+) reacts with H(2)O(2) and leads to the generation of (·)OH, which is responsible for the higher COD removal. However, overdosage H(2)O(2) will consume (·)OH generated in the electro-Fenton process and lead to the low COD removal. The COD removal efficiency decreased with the increased pH. The concentration of Fe(2+) ions was dependent on the solution pH, H(2)O(2) dosage and current density. The changes of organic characteristics in coagulation and oxidation process were differenced and evaluated using gel permeation chromatography, fluorescence excitation-emission scans and Fourier transform infrared spectroscopy. The fraction of the wastewater with aromatic structure and large molecular weight was decomposed into aliphatic structure and small molecular weight fraction in the electro-Fenton process. Copyright © 2012. Published by Elsevier Ltd.

Synthesis, crystal structures and spectroscopic properties of triazine-based hydrazone derivatives; a comparative experimental-theoretical study.

PubMed

Arshad, Muhammad Nadeem; Bibi, Aisha; Mahmood, Tariq; Asiri, Abdullah M; Ayub, Khurshid

2015-04-03

We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (1H and 13C) spectroscopic techniques and finally confirmed unequivocally by single crystal X-ray diffraction analysis. Experimental geometric parameters and spectroscopic properties of the triazine based hydrazones are compared with those obtained from density functional theory (DFT) studies. The model developed here comprises of geometry optimization at B3LYP/6-31G (d, p) level of DFT. Optimized geometric parameters of all four compounds showed excellent correlations with the results obtained from X-ray diffraction studies. The vibrational spectra show nice correlations with the experimental IR spectra. Moreover, the simulated absorption spectra also agree well with experimental results (within 10-20 nm). The molecular electrostatic potential (MEP) mapped over the entire stabilized geometries of the compounds indicated their chemical reactivates. Furthermore, frontier molecular orbital (electronic properties) and first hyperpolarizability (nonlinear optical response) were also computed at the B3LYP/6-31G (d, p) level of theory.

GAtor: A First-Principles Genetic Algorithm for Molecular Crystal Structure Prediction.

PubMed

Curtis, Farren; Li, Xiayue; Rose, Timothy; Vázquez-Mayagoitia, Álvaro; Bhattacharya, Saswata; Ghiringhelli, Luca M; Marom, Noa

2018-04-10

We present the implementation of GAtor, a massively parallel, first-principles genetic algorithm (GA) for molecular crystal structure prediction. GAtor is written in Python and currently interfaces with the FHI-aims code to perform local optimizations and energy evaluations using dispersion-inclusive density functional theory (DFT). GAtor offers a variety of fitness evaluation, selection, crossover, and mutation schemes. Breeding operators designed specifically for molecular crystals provide a balance between exploration and exploitation. Evolutionary niching is implemented in GAtor by using machine learning to cluster the dynamically updated population by structural similarity and then employing a cluster-based fitness function. Evolutionary niching promotes uniform sampling of the potential energy surface by evolving several subpopulations, which helps overcome initial pool biases and selection biases (genetic drift). The various settings offered by GAtor increase the likelihood of locating numerous low-energy minima, including those located in disconnected, hard to reach regions of the potential energy landscape. The best structures generated are re-relaxed and re-ranked using a hierarchy of increasingly accurate DFT functionals and dispersion methods. GAtor is applied to a chemically diverse set of four past blind test targets, characterized by different types of intermolecular interactions. The experimentally observed structures and other low-energy structures are found for all four targets. In particular, for Target II, 5-cyano-3-hydroxythiophene, the top ranked putative crystal structure is a Z' = 2 structure with P1̅ symmetry and a scaffold packing motif, which has not been reported previously.

Mussel adhesion is dictated by time-regulated secretion and molecular conformation of mussel adhesive proteins

NASA Astrophysics Data System (ADS)

Petrone, Luigi; Kumar, Akshita; Sutanto, Clarinda N.; Patil, Navinkumar J.; Kannan, Srinivasaraghavan; Palaniappan, Alagappan; Amini, Shahrouz; Zappone, Bruno; Verma, Chandra; Miserez, Ali

2015-10-01

Interfacial water constitutes a formidable barrier to strong surface bonding, hampering the development of water-resistant synthetic adhesives. Notwithstanding this obstacle, the Asian green mussel Perna viridis attaches firmly to underwater surfaces via a proteinaceous secretion (byssus). Extending beyond the currently known design principles of mussel adhesion, here we elucidate the precise time-regulated secretion of P. viridis mussel adhesive proteins. The vanguard 3,4-dihydroxy-L-phenylalanine (Dopa)-rich protein Pvfp-5 acts as an adhesive primer, overcoming repulsive hydration forces by displacing surface-bound water and generating strong surface adhesion. Using homology modelling and molecular dynamics simulations, we find that all mussel adhesive proteins are largely unordered, with Pvfp-5 adopting a disordered structure and elongated conformation whereby all Dopa residues reside on the protein surface. Time-regulated secretion and structural disorder of mussel adhesive proteins appear essential for optimizing extended nonspecific surface interactions and byssus' assembly. Our findings reveal molecular-scale principles to help the development of wet-resistant adhesives.

Structural and spectroscopic investigation of glycinium oxalurate

NASA Astrophysics Data System (ADS)

Kavitha, T.; Pasupathi, G.; Marchewka, M. K.; Anbalagan, G.; Kanagathara, N.

2017-09-01

Glycinium oxalurate (GO) single crystals has been synthesized and grown by the slow solvent evaporation method at room temperature. Single crystal X-ray diffraction study confirms that GO crystal crystallizes in the monoclinic system with centrosymmetric space group P121/c1. The grown crystals are built up from single protonated glycinium residues and single dissociated oxalurate anions. A combination of ionic and donor-acceptor hydrogen-bond interactions linking together the glycine and oxaluric acid residues forms a three-dimensional network. Hydrogen bonded network present in the crystal gives notable vibrational effect. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on HF and density functional theory B3LYP methods with 6-311++G(d,p) basis set. Frontier molecular orbital energies and other related electronic properties are calculated. The natural bonding orbital (NBO) charges have been calculated and interpreted. The molecular electrostatic potential map has been constructed and discussed in detail.

Performance Enhancement of Small Molecular Solar Cells by Bilayer Cathode Buffer.

PubMed

Sun, Qinjun; Zhao, Huanbin; Zhou, Miao; Gao, Liyan; Hao, Yuying

2016-04-01

An effective composite bilayer cathode buffer structure is proposed for use in small molecular solar cells. CsF was doped in Alq3 to form the first cathode buffer, leading to small serial resistances. BCP was used as the second cathode buffer to block the holes to the electrode. The optimized bilayer cathode buffer significantly increased the short circuit and fill factor of devices. By integrating this bilayer cathode buffer, the CuPc/C60 small molecular heterojunction cell exhibited a power conversion efficiency of up to 0.8%, which was an improvement of 56% compared to a device with only the Alq3 cathode buffer. Meanwhile, the bilayer cathode buffer still has a good protective effect on the performance of the device.

Study of percolation behavior depending on molecular structure design

NASA Astrophysics Data System (ADS)

Yu, Ji Woong; Lee, Won Bo

Each differently designed anisotropic nano-crystals(ANCs) are studied using Langevin dynamic simulation and their percolation behaviors are presented. Popular molecular dynamics software LAMMPS was used to design the system and perform the simulation. We calculated the minimum number density at which percolation occurs(i.e. percolation threshold), radial distribution function, and the average number of ANCs for a cluster. Electrical conductivity is improved when the number of transfers of electrons between ANCs, so called ''inter-hopping process'', which has the considerable contribution to resistance decreases and the number of inter-hopping process is directly related with the concentration of ANCs. Therefore, with the investigation of relationship between molecular architecture and percolation behavior, optimal design of ANC can be achieved.

Revisiting the blind tests in crystal structure prediction: accurate energy ranking of molecular crystals.

PubMed

Asmadi, Aldi; Neumann, Marcus A; Kendrick, John; Girard, Pascale; Perrin, Marc-Antoine; Leusen, Frank J J

2009-12-24

In the 2007 blind test of crystal structure prediction hosted by the Cambridge Crystallographic Data Centre (CCDC), a hybrid DFT/MM method correctly ranked each of the four experimental structures as having the lowest lattice energy of all the crystal structures predicted for each molecule. The work presented here further validates this hybrid method by optimizing the crystal structures (experimental and submitted) of the first three CCDC blind tests held in 1999, 2001, and 2004. Except for the crystal structures of compound IX, all structures were reminimized and ranked according to their lattice energies. The hybrid method computes the lattice energy of a crystal structure as the sum of the DFT total energy and a van der Waals (dispersion) energy correction. Considering all four blind tests, the crystal structure with the lowest lattice energy corresponds to the experimentally observed structure for 12 out of 14 molecules. Moreover, good geometrical agreement is observed between the structures determined by the hybrid method and those measured experimentally. In comparison with the correct submissions made by the blind test participants, all hybrid optimized crystal structures (apart from compound II) have the smallest calculated root mean squared deviations from the experimentally observed structures. It is predicted that a new polymorph of compound V exists under pressure.

Molecular and electronic structure of the peptide subunit of Geobacter sulfurreducens conductive pili from first principles.

PubMed

Feliciano, Gustavo T; da Silva, Antonio J R; Reguera, Gemma; Artacho, Emilio

2012-08-02

The respiration of metal oxides by the bacterium Geobacter sulfurreducens requires the assembly of a small peptide (the GS pilin) into conductive filaments termed pili. We gained insights into the contribution of the GS pilin to the pilus conductivity by developing a homology model and performing molecular dynamics simulations of the pilin peptide in vacuo and in solution. The results were consistent with a predominantly helical peptide containing the conserved α-helix region required for pilin assembly but carrying a short carboxy-terminal random-coiled segment rather than the large globular head of other bacterial pilins. The electronic structure of the pilin was also explored from first principles and revealed a biphasic charge distribution along the pilin and a low electronic HOMO-LUMO gap, even in a wet environment. The low electronic band gap was the result of strong electrostatic fields generated by the alignment of the peptide bond dipoles in the pilin's α-helix and by charges from ions in solution and amino acids in the protein. The electronic structure also revealed some level of orbital delocalization in regions of the pilin containing aromatic amino acids and in spatial regions of high resonance where the HOMO and LUMO states are, which could provide an optimal environment for the hopping of electrons under thermal fluctuations. Hence, the structural and electronic features of the pilin revealed in these studies support the notion of a pilin peptide environment optimized for electron conduction.

Next Generation Extended Lagrangian Quantum-based Molecular Dynamics

NASA Astrophysics Data System (ADS)

Negre, Christian

2017-06-01

A new framework for extended Lagrangian first-principles molecular dynamics simulations is presented, which overcomes shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while maintaining important advantages of the unified extended Lagrangian formulation of density functional theory pioneered by Car and Parrinello three decades ago. The new framework allows, for the first time, energy conserving, linear-scaling Born-Oppenheimer molecular dynamics simulations, which is necessary to study larger and more realistic systems over longer simulation times than previously possible. Expensive, self-consinstent-field optimizations are avoided and normal integration time steps of regular, direct Born-Oppenheimer molecular dynamics can be used. Linear scaling electronic structure theory is presented using a graph-based approach that is ideal for parallel calculations on hybrid computer platforms. For the first time, quantum based Born-Oppenheimer molecular dynamics simulation is becoming a practically feasible approach in simulations of +100,000 atoms-representing a competitive alternative to classical polarizable force field methods. In collaboration with: Anders Niklasson, Los Alamos National Laboratory.

Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models.

PubMed

Esposito, Emilio Xavier; Hopfinger, Anton J; Shao, Chi-Yu; Su, Bo-Han; Chen, Sing-Zuo; Tseng, Yufeng Jane

2015-10-01

Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted from the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints. Copyright © 2015 Elsevier Inc. All rights reserved.

Spectroscopic (FT-IR, FT-Raman, NMR and UV-Visible) and quantum chemical studies of molecular geometry, Frontier molecular orbital, NLO, NBO and thermodynamic properties of salicylic acid.

PubMed

Suresh, S; Gunasekaran, S; Srinivasan, S

2014-11-11

The solid phase FT-IR and FT-Raman spectra of 2-hydroxybenzoic acid (salicylic acid) have been recorded in the region 4000-400 and 4000-100 cm(-1) respectively. The optimized molecular geometry and fundamental vibrational frequencies are interpreted with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) method and a comparative study between Hartree Fork (HF) method at 6-311++G(d,p) level basis set. The calculated harmonic vibrational frequencies are scaled and they are compared with experimentally obtained FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated potential energy distribution (PED). The time dependent DFT method is employed to predict its absorption energy and oscillator strength. The linear polarizability (α) and the first order hyper polarizability (β) values of the investigated molecule have been computed. The electronic properties, such as HOMO and LUMO energies, molecular electrostatic potential (MEP) are also performed. Stability of the molecule arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Published by Elsevier B.V.

Structure and Li+ ion transport in a mixed carbonate/LiPF6 electrolyte near graphite electrode surfaces: a molecular dynamics study.

PubMed

Boyer, Mathew J; Vilčiauskas, Linas; Hwang, Gyeong S

2016-10-12

Electrolyte and electrode materials used in lithium-ion batteries have been studied separately to a great extent, however the structural and dynamical properties of the electrolyte-electrode interface still remain largely unexplored despite its critical role in governing battery performance. Using molecular dynamics simulations, we examine the structural reorganization of solvent molecules (cyclic ethylene carbonate : linear dimethyl carbonate 1 : 1 molar ratio doped with 1 M LiPF 6 ) in the vicinity of graphite electrodes with varying surface charge densities (σ). The interfacial structure is found to be sensitive to the molecular geometry and polarity of each solvent molecule as well as the surface structure and charge distribution of the negative electrode. We also evaluated the potential difference across the electrolyte-electrode interface, which exhibits a nearly linear variation with respect to σ up until the onset of Li + ion accumulation onto the graphite edges from the electrolyte. In addition, well-tempered metadynamics simulations are employed to predict the free-energy barriers to Li + ion transport through the relatively dense interfacial layer, along with analysis of the Li + solvation sheath structure. Quantitative analysis of the molecular arrangements at the electrolyte-electrode interface will help better understand and describe electrolyte decomposition, especially in the early stages of solid-electrolyte-interphase (SEI) formation. Moreover, the computational framework presented in this work offers a means to explore the effects of solvent composition, electrode surface modification, and operating temperature on the interfacial structure and properties, which may further assist in efforts to engineer the electrolyte-electrode interface leading to a SEI layer that optimizes battery performance.

Coupling Matched Molecular Pairs with Machine Learning for Virtual Compound Optimization.

PubMed

Turk, Samo; Merget, Benjamin; Rippmann, Friedrich; Fulle, Simone

2017-12-26

Matched molecular pair (MMP) analyses are widely used in compound optimization projects to gain insights into structure-activity relationships (SAR). The analysis is traditionally done via statistical methods but can also be employed together with machine learning (ML) approaches to extrapolate to novel compounds. The here introduced MMP/ML method combines a fragment-based MMP implementation with different machine learning methods to obtain automated SAR decomposition and prediction. To test the prediction capabilities and model transferability, two different compound optimization scenarios were designed: (1) "new fragments" which occurs when exploring new fragments for a defined compound series and (2) "new static core and transformations" which resembles for instance the identification of a new compound series. Very good results were achieved by all employed machine learning methods especially for the new fragments case, but overall deep neural network models performed best, allowing reliable predictions also for the new static core and transformations scenario, where comprehensive SAR knowledge of the compound series is missing. Furthermore, we show that models trained on all available data have a higher generalizability compared to models trained on focused series and can extend beyond chemical space covered in the training data. Thus, coupling MMP with deep neural networks provides a promising approach to make high quality predictions on various data sets and in different compound optimization scenarios.

Bayesian ensemble refinement by replica simulations and reweighting.

PubMed

Hummer, Gerhard; Köfinger, Jürgen

2015-12-28

We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We show that the strength of the restraints should scale linearly with the number of replicas to ensure convergence to the optimal Bayesian result in the limit of infinitely many replicas. In the "Bayesian inference of ensembles" method, we combine the replica and EROS approaches to accelerate the convergence. An adaptive algorithm can be used to sample directly from the optimal ensemble, without replicas. We discuss the incorporation of single-molecule measurements and dynamic observables such as relaxation parameters. The theoretical analysis of different Bayesian ensemble refinement approaches provides a basis for practical applications and a starting point for further investigations.

Bayesian ensemble refinement by replica simulations and reweighting

NASA Astrophysics Data System (ADS)

Hummer, Gerhard; Köfinger, Jürgen

2015-12-01

We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We show that the strength of the restraints should scale linearly with the number of replicas to ensure convergence to the optimal Bayesian result in the limit of infinitely many replicas. In the "Bayesian inference of ensembles" method, we combine the replica and EROS approaches to accelerate the convergence. An adaptive algorithm can be used to sample directly from the optimal ensemble, without replicas. We discuss the incorporation of single-molecule measurements and dynamic observables such as relaxation parameters. The theoretical analysis of different Bayesian ensemble refinement approaches provides a basis for practical applications and a starting point for further investigations.

The structural, electronic and spectroscopic properties of 4FPBAPE molecule: Experimental and theoretical study

NASA Astrophysics Data System (ADS)

Tanış, Emine; Babur Sas, Emine; Kurban, Mustafa; Kurt, Mustafa

2018-02-01

The experimental and theoretical study of 4-Formyl Phenyl Boronic Acid Pinacol Ester (4FPBAPE) molecule were performed in this work. 1H, 13C NMR and UV-Vis spectra were tested in dimethyl sulfoxide (DMSO). The structural, spectroscopic properties and energies of 4FPBAPE were obtained for two potential conformers from density functional theory (DFT) with B3LYP/6-311G (d, p) and CAM-B3LYP/6-311G (d, p) basis sets. The optimal geometry of those structures was obtained according to the position of oxygen atom upon determining the scan coordinates for each conformation. The most stable conformer was found as the A2 form. The fundamental vibrations were determined based on optimized structure in terms of total energy distribution. Electronic properties such as oscillator strength, wavelength, excitation energy, HOMO, LUMO and molecular electrostatic potential and structural properties such as radial distribution functions (RDF) and probability density depending on coordination number are presented. Theoretical results of 4-FPBAPE spectra were found to be compatible with observed spectra.

Long-wavelength room-temperature luminescence from InAs/GaAs quantum dots with an optimized GaAsSbN capping layer

PubMed Central

2014-01-01

An extensive study on molecular beam epitaxy growth conditions of quaternary GaAsSbN as a capping layer (CL) for InAs/GaAs quantum dots (QD) was carried out. In particular, CL thickness, growth temperature, and growth rate were optimized. Problems related to the simultaneous presence of Sb and N, responsible for a significant degradation of photoluminescence (PL), are thereby solved allowing the achievement of room-temperature (RT) emission. A particularly strong improvement on the PL is obtained when the growth rate of the CL is increased. This is likely due to an improvement in the structural quality of the quaternary alloy that resulted from reduced strain and composition inhomogeneities. Nevertheless, a significant reduction of Sb and N incorporation was found when the growth rate was increased. Indeed, the incorporation of N is intrinsically limited to a maximum value of approximately 1.6% when the growth rate is at 2.0 ML s−1. Therefore, achieving RT emission and extending it somewhat beyond 1.3 μm were possible by means of a compromise among the growth conditions. This opens the possibility of exploiting the versatility on band structure engineering offered by this QD-CL structure in devices working at RT. PACS 81.15.Hi (molecular beam epitaxy); 78.55.Cr (III-V semiconductors); 73.21.La (quantum dots) PMID:24438542

Physico-chemical, nutritional and infrared spectroscopy evaluation of an optimized soybean/corn flour extrudate.

PubMed

Guzmán-Ortiz, Fabiola Araceli; Hernández-Sánchez, Humberto; Yee-Madeira, Hernani; San Martín-Martínez, Eduardo; Robles-Ramírez, María Del Carmen; Rojas-López, Marlon; Berríos, Jose De J; Mora-Escobedo, Rosalva

2015-07-01

A central composite design using RMS (Response Surface Methodology) successfully described the effect of independent variables (feed moisture, die temperature and soybean proportion) on the specific parameters of product quality as expansion index (EI), water absorption index (WAI), water solubility index (WSI) and total color difference (ΔE) studied. The regression model indicated that EI, WAI, WSI and ΔE were significant (p < 0.05) with coefficients of determination (R(2)) of 0.7371, 0.7588, 0.7622, 0.8150, respectively. The optimized processing conditions were obtained with 25.8 % feed moisture, 160 °C die temperature and 58 %/42 % soybean/corn proportion. It was not found statistically changes in amino acid profile due to extrusion process. The electrophoretic profile of extruded soybean/corn mix presented low intensity molecular weight bands, compared to the unprocessed sample. The generation of low molecular weight polypeptides was associated to an increased in In vitro protein digestibility (IVPD) of the extrudate. The FTIR spectra of the soybean/corn mix before and after extrusion showed that the α-helix structure remained unchanged after extrusion. However, the band associated with β-sheet structure showed to be split into two bands at 1624 and 1640 cm(-1) . The changes in the β-sheet structures may be also associated to the increased in IVPD in the extruded sample.

Theoretical studies on the possible sensitizers of DSSC: Nanocomposites of graphene quantum dot hybrid phthalocyanine/tetrabenzoporphyrin/tetrabenzotriazaporphyrins/cis-tetrabenzodiazaporphyrins/tetrabenzomonoazaporphyrins and their Cu-metallated macrocycles

NASA Astrophysics Data System (ADS)

Gao, Feng; Yang, Chuan-Lu; Wang, Mei-Shan; Ma, Xiao-Guang; Liu, Wen-Wang

2018-04-01

The feasibility of nanocomposites of cir-coronene graphene quantum dot (GQD) with phthalocyanine, tetrabenzoporphyrin, tetrabenzotriazaporphyrins, cis-tetrabenzodiazaporphyrins, tetrabenzomonoazaporphyrins and their Cu-metallated macrocycles as a sensitizer of dye-sensitized solar cells (DSSC) are investigated. Based on the first principles density functional theory (DFT), the geometrical structures of the separate GQD and 10 macrocycles, and their hybridized nanocomposites are fully optimized. The energy stabilities of the obtained structures are confirmed by harmonic frequency analysis. The optical absorptions of the optimized structures are calculated with time-dependent DFT. The feasibility of the nanocomposites as the sensitizer of DSSC is examined by the charge spatial separation, the electron transfer, the molecular orbital energy levels of the nanocomposites and the electrolyte, and the conduction band minimum of TiO2 electrode. The results demonstrate that all the nanocomposites have enhanced absorptions in the visible light range, and their molecular orbital energies satisfy the requirement of sensitizers. However, only two of the ten considered nanocomposites demonstrate significantly charge spatial separation. The GQD-Cu-TBP is identified as the most favorable candidate sensitizer of DSSC by the most enhanced in optical absorption, obvious charge spatial separation, suitable LUMO energy levels and driving force for electron transfer, and low recombination rate of electron and hole.

Structural, physicochemical characterization, theoretical studies of carboxamides and their Cu(II), Zn(II) complexes having antibacterial activities against E. coli

NASA Astrophysics Data System (ADS)

Aktan, Ebru; Gündüzalp, Ayla Balaban; Özmen, Ümmühan Özdemir

2017-01-01

The carboxamides; N,N‧-bis(thiophene-2-carboxamido)-1,3-diaminopropanol (L1) and N,N‧-bis(furan-2-carboxamido)-1,3-diaminopropanol (L2) were synthesized and characterized using 1H NMR, 13C NMR, LC-MS and FT-IR spectrum. The molecular geometries of these molecules were optimized by DFT/B3LYP method with 6-311G(d,p) basis set in Gaussian 09 software. The geometrical parameters, frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) mapped surfaces were calculated by the same basis set. Dinuclear Cu(II) and Zn(II) complexes having general formula as [MLCl]2Cl2.nH2O (in which M = Cu(II),Zn(II); n = 0,2) were also synthesized and characterized using LC-MS and FT-IR spectrum, thermogravimetric analysis (TGA/DTA curves), magnetic moments and molar conductivities. Coordination was found to be through carbonyl oxygen and two chlorine atoms as bridging in distorted tetrahedral geometry. The optimized structures, geometrical parameters, frontier molecular orbitals (FMOs) and dipole moments of metal complexes were also obtained by DFT/B3LYP method with LanL2DZ basis set. Antibacterial activities of the compounds were screened against E. coli using microdilution method (MIC's in μg/mL). The activity results show that the corresponding compounds exhibit good to moderate antibacterial effects when compared with sulfamethoxazole and sulfisoxazole antibiotics as positive controls. Also, metal complexes have remarkable increase in their activities than parent ligands against E. coli which is mostly effected by [Cu(L2)Cl]2Cl2 complex as potential antibacterial agent.

A nanoscale study of charge extraction in organic solar cells: the impact of interfacial molecular configurations.

PubMed

Tang, Fu-Ching; Wu, Fu-Chiao; Yen, Chia-Te; Chang, Jay; Chou, Wei-Yang; Gilbert Chang, Shih-Hui; Cheng, Horng-Long

2015-01-07

In the optimization of organic solar cells (OSCs), a key problem lies in the maximization of charge carriers from the active layer to the electrodes. Hence, this study focused on the interfacial molecular configurations in efficient OSC charge extraction by theoretical investigations and experiments, including small molecule-based bilayer-heterojunction (sm-BLHJ) and polymer-based bulk-heterojunction (p-BHJ) OSCs. We first examined a well-defined sm-BLHJ model system of OSC composed of p-type pentacene, an n-type perylene derivative, and a nanogroove-structured poly(3,4-ethylenedioxythiophene) (NS-PEDOT) hole extraction layer. The OSC with NS-PEDOT shows a 230% increment in the short circuit current density compared with that of the conventional planar PEDOT layer. Our theoretical calculations indicated that small variations in the microscopic intermolecular interaction among these interfacial configurations could induce significant differences in charge extraction efficiency. Experimentally, different interfacial configurations were generated between the photo-active layer and the nanostructured charge extraction layer with periodic nanogroove structures. In addition to pentacene, poly(3-hexylthiophene), the most commonly used electron-donor material system in p-BHJ OSCs was also explored in terms of its possible use as a photo-active layer. Local conductive atomic force microscopy was used to measure the nanoscale charge extraction efficiency at different locations within the nanogroove, thus highlighting the importance of interfacial molecular configurations in efficient charge extraction. This study enriches understanding regarding the optimization of the photovoltaic properties of several types of OSCs by conducting appropriate interfacial engineering based on organic/polymer molecular orientations. The ultimate power conversion efficiency beyond at least 15% is highly expected when the best state-of-the-art p-BHJ OSCs are combined with present arguments.

The sintered microsphere matrix for bone tissue engineering: in vitro osteoconductivity studies.

PubMed

Borden, Mark; Attawia, Mohamed; Laurencin, Cato T

2002-09-05

A tissue engineering approach has been used to design three-dimensional synthetic matrices for bone repair. The osteoconductivity and degradation profile of a novel polymeric bone-graft substitute was evaluated in an in vitro setting. Using the copolymer poly(lactide-co-glycolide) [PLAGA], a sintering technique based on microsphere technology was used to fabricate three-dimensional porous scaffolds for bone regeneration. Osteoblasts and fibroblasts were seeded onto a 50:50 PLAGA scaffold. Morphologic evaluation through scanning electron microscopy demonstrated that both cell types attached and spread over the scaffold. Cells migrated through the matrix using cytoplasmic extensions to bridge the structure. Cross-sectional images indicated that cellular proliferation had penetrated into the matrix approximately 700 microm from the surface. Examination of the surfaces of cell/matrix constructs demonstrated that cellular proliferation had encompassed the pores of the matrix by 14 days of cell culture. With the aim of optimizing polymer composition and polymer molecular weight, a degradation study was conducted utilizing the matrix. The results demonstrate that degradation of the sintered matrix is dependent on molecular weight, copolymer ratio, and pore volume. From this data, it was determined that 75:25 PLAGA with an initial molecular weight of 100,000 has an optimal degradation profile. These studies show that the sintered microsphere matrix has an osteoconductive structure capable of functioning as a cellular scaffold with a degradation profile suitable for bone regeneration. Copyright 2002 Wiley Periodicals, Inc.

Molecular structure, vibrational spectra and DFT computational studies of melaminium N-acetylglycinate dihydrate

NASA Astrophysics Data System (ADS)

Tanak, H.; Pawlus, K.; Marchewka, M. K.

2016-10-01

Melaminium N-acetylglycinate dihydrate, an organic material has been synthesized and characterized by X-ray diffraction, FT-IR, and FT-Raman spectroscopies for the protiated and deuteriated crystals. The title complex crystallizes in the triclinic system, and the space group is P-1 with a = 5.642(1) Å, b = 7.773(2) Å, c = 15.775(3) Å, α = 77.28(1)°, β = 84.00(1)°, γ = 73.43(1)° and Z = 2. The molecular geometry, vibrational frequencies and intensity of the vibrational bands have been interpreted with the aid of structure optimization based on density functional method (B3LYP) with the 6-311++G(d,p) basis set. The obtained vibrational wavenumbers and optimized geometric parameters were seen to be in good agreement with the experimental data. The intermolecular hydrogen bonding interactions of the title compound have been investigated using the natural bonding orbital analysis. It reveals that the O-H···O, N-H···N and N-H···O intermolecular interactions significantly influence crystal packing of this molecule. The non-linear optical properties are also addressed theoretically. The predicted NLO properties of the title compound are much greater than ones of urea. In addition, DFT calculations of the title compound, molecular electrostatic potential, thermodynamic properties, frontier orbitals and chemical reactivity descriptors were also performed at 6-311++G(d,p) level of theory.

Thermally induced disintegration of the oligomeric structure of alphaB-crystallin mutant F28S is associated with diminished chaperone activity.

PubMed

Kelley, Patrick B; Abraham, Edathara C

2003-10-01

alphaB-crystallin, a member of the small heat-shock protein (hsp) family of proteins, is able to function as a molecular chaperone by protecting other proteins from stress-induced aggregation by recognizing and binding to partially unfolded species of damaged proteins. The present work has investigated the role of phenylalanine-28 (F28) of the 22RLFDQFF28 region of alphaB-crystallin in maintaining chaperone function and oligomeric structure under physiological condition and under thermal stress. Bovine alphaB-crystallin was cloned for the first time and the cDNA sequence revealed greater than 90% homology to that of human, rat and mouse alphaB-crystallins. F28 was mutated to a serine followed by expression of the mutant F28S and the wild-type alphaB (alphaB-wt) in E. coli and subsequent purification of the protein by size-exclusion chromatography. Secondary and tertiary structure analyses showed some structural changes in the mutant. Chaperone activity and oligomeric size of the mutant was unchanged at 37 degrees C whereas at 58 degrees C the chaperone activity was significantly decreased and the oligomeric size ranged from low molecular weight to high molecular weight showing disintegration of the oligomeric structure. The data support the idea that the participation of large oligomeric structure rather than smaller units is required to have optimal chaperone activity and the hydrophobic F28 residue is needed for maintaining the native oligomeric structure under thermal stress.

Molecular descriptor subset selection in theoretical peptide quantitative structure-retention relationship model development using nature-inspired optimization algorithms.

PubMed

Žuvela, Petar; Liu, J Jay; Macur, Katarzyna; Bączek, Tomasz

2015-10-06

In this work, performance of five nature-inspired optimization algorithms, genetic algorithm (GA), particle swarm optimization (PSO), artificial bee colony (ABC), firefly algorithm (FA), and flower pollination algorithm (FPA), was compared in molecular descriptor selection for development of quantitative structure-retention relationship (QSRR) models for 83 peptides that originate from eight model proteins. The matrix with 423 descriptors was used as input, and QSRR models based on selected descriptors were built using partial least squares (PLS), whereas root mean square error of prediction (RMSEP) was used as a fitness function for their selection. Three performance criteria, prediction accuracy, computational cost, and the number of selected descriptors, were used to evaluate the developed QSRR models. The results show that all five variable selection methods outperform interval PLS (iPLS), sparse PLS (sPLS), and the full PLS model, whereas GA is superior because of its lowest computational cost and higher accuracy (RMSEP of 5.534%) with a smaller number of variables (nine descriptors). The GA-QSRR model was validated initially through Y-randomization. In addition, it was successfully validated with an external testing set out of 102 peptides originating from Bacillus subtilis proteomes (RMSEP of 22.030%). Its applicability domain was defined, from which it was evident that the developed GA-QSRR exhibited strong robustness. All the sources of the model's error were identified, thus allowing for further application of the developed methodology in proteomics.

A Comparison of Quantum and Molecular Mechanical Methods to Estimate Strain Energy in Druglike Fragments.

PubMed

Sellers, Benjamin D; James, Natalie C; Gobbi, Alberto

2017-06-26

Reducing internal strain energy in small molecules is critical for designing potent drugs. Quantum mechanical (QM) and molecular mechanical (MM) methods are often used to estimate these energies. In an effort to determine which methods offer an optimal balance in accuracy and performance, we have carried out torsion scan analyses on 62 fragments. We compared nine QM and four MM methods to reference energies calculated at a higher level of theory: CCSD(T)/CBS single point energies (coupled cluster with single, double, and perturbative triple excitations at the complete basis set limit) calculated on optimized geometries using MP2/6-311+G**. The results show that both the more recent MP2.X perturbation method as well as MP2/CBS perform quite well. In addition, combining a Hartree-Fock geometry optimization with a MP2/CBS single point energy calculation offers a fast and accurate compromise when dispersion is not a key energy component. Among MM methods, the OPLS3 force field accurately reproduces CCSD(T)/CBS torsion energies on more test cases than the MMFF94s or Amber12:EHT force fields, which struggle with aryl-amide and aryl-aryl torsions. Using experimental conformations from the Cambridge Structural Database, we highlight three example structures for which OPLS3 significantly overestimates the strain. The energies and conformations presented should enable scientists to estimate the expected error for the methods described and we hope will spur further research into QM and MM methods.

Molecular self-assembly approaches for supramolecular electronic and organic electronic devices

NASA Astrophysics Data System (ADS)

Yip, Hin-Lap

Molecular self-assembly represents an efficient bottom-up strategy to generate structurally well-defined aggregates of semiconducting pi-conjugated materials. The capability of tuning the chemical structures, intermolecular interactions and nanostructures through molecular engineering and novel materials processing renders it possible to tailor a large number of unprecedented properties such as charge transport, energy transfer and light harvesting. This approach does not only benefit traditional electronic devices based on bulk materials, but also generate a new research area so called "supramolecular electronics" in which electronic devices are built up with individual supramolecular nanostructures with size in the sub-hundred nanometers range. My work combined molecular self-assembly together with several novel materials processing techniques to control the nucleation and growth of organic semiconducting nanostructures from different type of pi-conjugated materials. By tailoring the interactions between the molecules using hydrogen bonds and pi-pi stacking, semiconducting nanoplatelets and nanowires with tunable sizes can be fabricated in solution. These supramolecular nanostructures were further patterned and aligned on solid substrates through printing and chemical templating methods. The capability to control the different hierarchies of organization on surface provides an important platform to study their structural-induced electronic properties. In addition to using molecular self-assembly to create different organic nanostructures, functional self-assembled monolayer (SAM) formed by spontaneous chemisorption on surfaces was used to tune the interfacial property in organic solar cells. Devices showed dramatically improved performance when appropriate SAMs were applied to optimize the contact property for efficiency charge collection.

A molecular dynamics study of the role of molecular water on the structure and mechanics of amorphous geopolymer binders.

PubMed

Sadat, Mohammad Rafat; Bringuier, Stefan; Asaduzzaman, Abu; Muralidharan, Krishna; Zhang, Lianyang

2016-10-07

In this paper, molecular dynamics simulations are used to study the effect of molecular water and composition (Si/Al ratio) on the structure and mechanical properties of fully polymerized amorphous sodium aluminosilicate geopolymer binders. The X-ray pair distribution function for the simulated geopolymer binder phase showed good agreement with the experimentally determined structure in terms of bond lengths of the various atomic pairs. The elastic constants and ultimate tensile strength of the geopolymer binders were calculated as a function of water content and Si/Al ratio; while increasing the Si/Al ratio from one to three led to an increase in the respective values of the elastic stiffness and tensile strength, for a given Si/Al ratio, increasing the water content decreased the stiffness and strength of the binder phase. An atomic-scale analysis showed a direct correlation between water content and diffusion of alkali ions, resulting in the weakening of the AlO 4 tetrahedral structure due to the migration of charge balancing alkali ions away from the tetrahedra, ultimately leading to failure. In the presence of water molecules, the diffusion behavior of alkali cations was found to be particularly anomalous, showing dynamic heterogeneity. This paper, for the first time, proves the efficacy of atomistic simulations for understanding the effect of water in geopolymer binders and can thus serve as a useful design tool for optimizing composition of geopolymers with improved mechanical properties.

"Vibrational spectroscopic analysis and molecular docking studies of (E)-4-methoxy-N‧-(4-methylbenzylidene) benzohydrazide by DFT"

NASA Astrophysics Data System (ADS)

Maheswari, R.; Manjula, J.

2016-07-01

(E)-4-methoxy-N‧-(4-methylbenzylidene)benzohydrazide (4MN'MBH) a novel, organic, hydrazone Schiff base compound was synthesized and its structure was characterized by Fourier Transform Infrared (4000-400 cm-1), Fourier Transform Raman (3500-50 cm-1), Ultraviolet-Visible (200-800 nm) and 1H and 13C NMR spectroscopic analysis. Optimized molecular structure, vibrational frequencies and corresponding vibrational assignments regarding 4MN'MBH has become screened tentatively as well as hypothetically utilizing Gaussian09Wprogram package. Potential energy distributions of the normal modes of vibrations connected with vibrations are generally accomplished by applying VEDA program. Natural Bonding Orbital (NBO) assessment was completed with a reason to clarify charge transfer or conjugative interaction, the intra-molecular-hybridization and delocalization of electron density within the molecule. Electronic transitions were studied employing UV-Visible spectrum and the observed values were compared with theoretical values. 1H and13C NMR spectral assessment had been made with choosing structure property relationship by chemical shifts along with magnetic shielding effects of title compound. The first order hyperpolarizability (β0) and related properties (β, α0 and Δα) of 4MN'MBH were calculated. The computed first order hyperpolarizability commensurate with the documented worth of very similar structure and could be an interesting thing for more experiments on non linear optics. Molecular docking study has been performed by in silico method to analysis their antituberculosis aspects against Enoyl acyl carrier protein reductase (Mycobacterium tuberculosis InhA) protein.

Using experimental studies and theoretical calculations to analyze the molecular mechanism of coumarin, p-hydroxybenzoic acid, and cinnamic acid

NASA Astrophysics Data System (ADS)

Hsieh, Tiane-Jye; Su, Chia-Ching; Chen, Chung-Yi; Liou, Chyong-Huey; Lu, Li-Hwa

2005-05-01

Three natural products, Coumarin ( 1), p-hydroxybenzoic acid ( 2), trans-cinnamic acid ( 3) were isolated from the natural plant of indigenous cinnamon and the structures including relative stereochemistry were elucidated on the basis of spectroscopic data and theoretical calculations. Their sterochemical structures were determined by NMR spectroscopy, mass spectroscopy, and X-ray crystallography. The p-hydroxybenzoic acid complex with water is reported to show the existence of two hydrogen bonds. The two hydrogen bonds are formed in the water molecule of two hydrogen-accepting oxygen of carbonyl group of the p-hydroxybenzoic acid. The intermolecular interaction two hydrogen bond of the model system of the water- p-hydroxybenzoic acid was investigated. An experimental study and a theoretical analysis using the B3LYP/6-31G* method in the GAUSSIAN-03 package program were conducted on the three natural products. The theoretical results are supplemented by experimental data. Optimal geometric structures of three compounds were also determined. The calculated molecular mechanics compared quite well with those obtained from the experimental data. The ionization potentials, highest occupied molecular orbital energy, lowest unoccupied molecular orbital energy, energy gaps, heat of formation, atomization energies, and vibration frequencies of the compounds were also calculated. The results of the calculations show that three natural products are stable molecules with high reactive and various other physical properties. The study also provided an explicit understanding of the sterochemical structure and thermodynamic properties of the three natural products.

Structural investigation of a self-assembled monolayer material 5-[(3-methylphenyl) (phenyl) amino] isophthalic acid for organic light-emitting devices.

PubMed

Saş, E Babur; Kurt, M; Can, M; Okur, S; İçli, S; Demiç, S

2014-12-10

The molecular structure and vibrations of 5-[(3-methylphenyl) (phenyl) amino] isophthalic acid (MePIFA) were investigated by infrared and Raman spectroscopies, UV-Vis, (1)H and (13)C NMR spectroscopic techniques and NBO analysis. FT-IR, FT-Raman and dispersive Raman spectra were recorded in the solid phase. (1)H and (13)C NMR spectra and UV-Vis spectrum were recorded in DMSO solution. HOMO-LUMO analysis and molecular electrostatic potential (MEP) analysis were performed. The theoretical calculations for the molecular structure and spectroscopies were performed with DFT (B3LYP) and 6-311G(d,p) basis set calculations using the Gaussian 09 program. After the geometry of the molecule was optimized, vibration wavenumbers and fundamental vibration wavenumbers were assigned on the basis of the potential energy distribution (PED) of the vibrational modes calculated with VEDA 4 program. The total (TDOS), partial (PDOS) density of state and overlap population density of state (OPDOS) diagrams analysis were made using GaussSum 2.2 program. The results of theoretical calculations for the spectra of the title compound were compared with the observed spectra. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural investigation of a self-assembled monolayer material 5-[(3-methylphenyl) (phenyl) amino] isophthalic acid for organic light-emitting devices

NASA Astrophysics Data System (ADS)

Saş, E. Babur; Kurt, M.; Can, M.; Okur, S.; İçli, S.; Demiç, S.

2014-12-01

The molecular structure and vibrations of 5-[(3-methylphenyl) (phenyl) amino] isophthalic acid (MePIFA) were investigated by infrared and Raman spectroscopies, UV-Vis, 1H and 13C NMR spectroscopic techniques and NBO analysis. FT-IR, FT-Raman and dispersive Raman spectra were recorded in the solid phase. 1H and 13C NMR spectra and UV-Vis spectrum were recorded in DMSO solution. HOMO-LUMO analysis and molecular electrostatic potential (MEP) analysis were performed. The theoretical calculations for the molecular structure and spectroscopies were performed with DFT (B3LYP) and 6-311G(d,p) basis set calculations using the Gaussian 09 program. After the geometry of the molecule was optimized, vibration wavenumbers and fundamental vibration wavenumbers were assigned on the basis of the potential energy distribution (PED) of the vibrational modes calculated with VEDA 4 program. The total (TDOS), partial (PDOS) density of state and overlap population density of state (OPDOS) diagrams analysis were made using GaussSum 2.2 program. The results of theoretical calculations for the spectra of the title compound were compared with the observed spectra.

Molecular Level Structure and Dynamics of Electrolytes Using 17O Nuclear Magnetic Resonance Spectroscopy

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

Murugesan, Vijayakumar; Han, Kee Sung; Hu, Jianzhi

2017-03-19

Electrolytes help harness the energy from electrochemical processes by serving as solvents and transport media for redox-active ions. Molecular-level interactions between ionic solutes and solvent molecules – commonly referred to as solvation phenomena – give rise to many functional properties of electrolytes such as ionic conductivity, viscosity, and stability. It is critical to understand the evolution of solvation phenomena as a function of competing counterions and solvent mixtures to predict and design the optimal electrolyte for a target application. Probing oxygen environments is of great interest as oxygens are located at strategic molecular sites in battery solvents and are directlymore » involved in inter- and intramolecular solvation interactions. NMR signals from 17O nuclei in battery electrolytes offer nondestructive bulk measurements of isotropic shielding, electric field gradient tensors, and transverse and longitudinal relaxation rates, which are excellent means for probing structure, bonding, and dynamics of both solute and solvent molecules. This article describes the use of 17O NMR spectroscopy in probing the solvation structures of various electrolyte systems ranging from transition metal ions in aqueous solution to lithium cations in organic solvent mixtures.« less

Simplified molecular input line entry system-based: QSAR modelling for MAP kinase-interacting protein kinase (MNK1).

PubMed

Begum, S; Achary, P Ganga Raju

2015-01-01

Quantitative structure-activity relationship (QSAR) models were built for the prediction of inhibition (pIC50, i.e. negative logarithm of the 50% effective concentration) of MAP kinase-interacting protein kinase (MNK1) by 43 potent inhibitors. The pIC50 values were modelled with five random splits, with the representations of the molecular structures by simplified molecular input line entry system (SMILES). QSAR model building was performed by the Monte Carlo optimisation using three methods: classic scheme; balance of correlations; and balance correlation with ideal slopes. The robustness of these models were checked by parameters as rm(2), r(*)m(2), [Formula: see text] and randomisation technique. The best QSAR model based on single optimal descriptors was applied to study in vitro structure-activity relationships of 6-(4-(2-(piperidin-1-yl) ethoxy) phenyl)-3-(pyridin-4-yl) pyrazolo [1,5-a] pyrimidine derivatives as a screening tool for the development of novel potent MNK1 inhibitors. The effects of alkyl group, -OH, -NO2, F, Cl, Br, I, etc. on the IC50 values towards the inhibition of MNK1 were also reported.

Temperature-accelerated molecular dynamics gives insights into globular conformations sampled in the free state of the AC catalytic domain.

PubMed

Selwa, Edithe; Huynh, Tru; Ciccotti, Giovanni; Maragliano, Luca; Malliavin, Thérèse E

2014-10-01

The catalytic domain of the adenyl cyclase (AC) toxin from Bordetella pertussis is activated by interaction with calmodulin (CaM), resulting in cAMP overproduction in the infected cell. In the X-ray crystallographic structure of the complex between AC and the C terminal lobe of CaM, the toxin displays a markedly elongated shape. As for the structure of the isolated protein, experimental results support the hypothesis that more globular conformations are sampled, but information at atomic resolution is still lacking. Here, we use temperature-accelerated molecular dynamics (TAMD) simulations to generate putative all-atom models of globular conformations sampled by CaM-free AC. As collective variables, we use centers of mass coordinates of groups of residues selected from the analysis of standard molecular dynamics (MD) simulations. Results show that TAMD allows extended conformational sampling and generates AC conformations that are more globular than in the complexed state. These structures are then refined via energy minimization and further unrestrained MD simulations to optimize inter-domain packing interactions, thus resulting in the identification of a set of hydrogen bonds present in the globular conformations. © 2014 Wiley Periodicals, Inc.

The structure of carbon nanotubes formed of graphene layers L4-8, L5-7, L3-12, L4-6-12

NASA Astrophysics Data System (ADS)

Shapovalova, K. E.; Belenkov, E. A.

2017-11-01

We geometrically calculate the optimized structure of nanotubes based on the graphene layers, using the method of molecular mechanics MM+. It was found that only the nanotubes, based on the graphene layers L4-8, L5-7, L3-12, L4-6-12, have a cylindrical form. Calculations of the sublimation energy, carried out using the semi-empirical quantum-mechanic method PM3, show that energy increases with the increase of nanotube diameters.

Spectral studies of 2-pyrazoline derivatives: structural elucidation through single crystal XRD and DFT calculations.

PubMed

Chinnaraja, D; Rajalakshmi, R; Srinivasan, T; Velmurugan, D; Jayabharathi, J

2014-04-24

A series of biologically active N-thiocarbamoyl pyrazoline derivatives have been synthesized using anhydrous potassium carbonate as the catalyst. All the synthesized compounds were characterized by FT-IR, (1)H NMR, (13)C NMR spectral studies, LCMS, CHN Analysis and X-ray diffraction analysis (compound 7). In order to supplement the XRD parameters, molecular modelling was carried out by Gaussian 03W. From the optimized structure, the energy, dipolemoment and HOMO-LUMO energies of all the systems were calculated. Copyright © 2014 Elsevier B.V. All rights reserved.

Spectroscopic investigation of some building blocks of organic conductors: A comparative study

NASA Astrophysics Data System (ADS)

Mukherjee, V.; Yadav, T.

2017-04-01

Theoretical molecular structures and IR and Raman spectra of di and tetra methyl substituted tetrathiafulvalene and tetraselenafulvalene molecules have been studied. These molecules belong to the organic conductor family and are immensely used as building blocks of several organic conducting devices. The Hartree-Fock and density functional theory with exchange functional B3LYP have been employed for computational purpose. We have also performed normal coordinate analysis to scale the theoretical frequencies and to calculate potential energy distributions for the conspicuous assignments. The exciting frequency and temperature dependent Raman spectra have also presented. Optimization results reveal that the sulphur derivatives possess boat shape while selenium derivatives possess planner structures. Natural bond orbitals analysis has also been performed to study second order interaction between donors and acceptors and to compute molecular orbital occupancy and energy.

Molecular dynamics study on glycolic acid in the physiological salt solution

NASA Astrophysics Data System (ADS)

Matsunaga, S.

2018-05-01

Molecular dynamics (MD) study on glycolic acid in the physiological salt solution has been performed, which is a model of a biofuel cell. The structure and charge distribution of glycolic acid in aqueous solution used in MD is beforehand optimized by Gaussian09 utilizing the density functional theory. MD is performed in the NTV constant condition, i.e. the number of particles, temperature, and volume of MD cell are definite. The structure difference of the glycolic acid and oxalic acid is detected by the water distribution around the molecules using the pair distribution functions, gij(r), and the frequency dependent diffusion coefficients, Di(ν). The anomalous dielectric constant of the solution, i.e. about 12 times larger than that of water, has been obtained, which may be attributed to the ion pair formation in the solution.

Comparison of molecular structure of alkali metal o-, m- and p-nitrobenzoates

NASA Astrophysics Data System (ADS)

Regulska, E.; Świsłocka, R.; Samsonowicz, M.; Lewandowski, W.

2008-09-01

The influence of nitro-substituent in ortho, meta and para positions as well as lithium, sodium, potassium, rubidium and cesium on the electronic system of aromatic ring and the distribution of electronic charge in carboxylic group of the nitrobenzoates were estimated. Optimized geometrical structures were calculated (B3LYP/6-311++G ∗∗). To make quantitative evaluation of aromaticity of studied molecules the geometric (A J, BAC, I 6 and HOMA) as well as magnetic (NICS) aromaticity indices were calculated. Electronic charge distribution was also examined by molecular spectroscopic study, which may be the source of quality criterion for aromaticity. Experimental and theoretical FT-IR, FT-Raman and NMR ( 1H and 13C) spectra of the title compounds were analyzed. The calculated parameters were compared to experimental characteristics of these molecules.

Designing Isoform-selective Inhibitors Against Classical HDACs for Effective Anticancer Therapy: Insight and Perspectives from In Silico.

PubMed

Ganai, Shabir Ahmad

2018-01-01

Histone deacetylase inhibitors, the small molecules modulating the biological activity of histone deacetylases are emerging as potent chemotherapeutic agents. Despite their considerable therapeutic benefits in disease models, the lack of isoform specificity culminates in debilitating off target effects, raising serious concerns regarding their applicability. This emphasizes the pressing and unmet medical need of designing isoform selective inhibitors for safe and effective anticancer therapy. Keeping these grim facts in view, the current article sheds light on structural basis of off-targeting. Furthermore, the article discusses extensively the role of in silico strategies such as Molecular Docking, Molecular Dynamics Simulation and Energetically-optimized structure based pharmacophore approach in designing on-target inhibitors against classical HDACs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Theoretical investigations of two adamantane derivatives: A combined X-ray, DFT, QTAIM analysis and molecular docking

NASA Astrophysics Data System (ADS)

Al-Wahaibi, Lamya H.; Sujay, Subramaniam; Muthu, Gangadharan Ganesh; El-Emam, Ali A.; Venkataramanan, Natarajan S.; Al-Omary, Fatmah A. M.; Ghabbour, Hazem A.; Percino, Judith; Thamotharan, Subbiah

2018-05-01

A detailed structural analysis of two adamantane derivatives namely, ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(phenyl)isothioureido]acetate I and ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(4-fluorophenyl)isothioureido]acetate II is carried out to understand the effect of fluorine substitution. The introduction of fluorine atom alters the crystal packing and is completely different from its parent compound. The fluorine substitution drastically reduced the intermolecular H⋯H contacts and this reduction is compensated by intermolecular F⋯H and F⋯F contacts. The relative contributions of various intermolecular contacts present in these structures were quantified using Hirshfeld surface analysis. Energetically significant molecular pairs were identified from the crystal structures of these compounds using PIXEL method. The structures of I and II are optimized in gas and solvent phases using the B3LYP-D3/6-311++G(d,p) level of theory. The quantum theory of atoms-in-molecules (QTAIM) analysis was carried out to estimate the strengths of various intermolecular contacts present in these molecular dimers. The results suggest that the Hsbnd H bonding take part in the stabilization of crystal structures. The experimental and theoretical UV-Vis results show the variations in HOMO and LUMO energy levels. In silico docking analysis indicates that both compounds I and II may exhibit inhibitory activity against 11-β-hydroxysteroid dehydrogenase 1 (11-β-HSD1).

Optimization of the GBMV2 implicit solvent force field for accurate simulation of protein conformational equilibria.

PubMed

Lee, Kuo Hao; Chen, Jianhan

2017-06-15

Accurate treatment of solvent environment is critical for reliable simulations of protein conformational equilibria. Implicit treatment of solvation, such as using the generalized Born (GB) class of models arguably provides an optimal balance between computational efficiency and physical accuracy. Yet, GB models are frequently plagued by a tendency to generate overly compact structures. The physical origins of this drawback are relatively well understood, and the key to a balanced implicit solvent protein force field is careful optimization of physical parameters to achieve a sufficient level of cancellation of errors. The latter has been hampered by the difficulty of generating converged conformational ensembles of non-trivial model proteins using the popular replica exchange sampling technique. Here, we leverage improved sampling efficiency of a newly developed multi-scale enhanced sampling technique to re-optimize the generalized-Born with molecular volume (GBMV2) implicit solvent model with the CHARMM36 protein force field. Recursive optimization of key GBMV2 parameters (such as input radii) and protein torsion profiles (via the CMAP torsion cross terms) has led to a more balanced GBMV2 protein force field that recapitulates the structures and stabilities of both helical and β-hairpin model peptides. Importantly, this force field appears to be free of the over-compaction bias, and can generate structural ensembles of several intrinsically disordered proteins of various lengths that seem highly consistent with available experimental data. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Global optimization of cholic acid aggregates

NASA Astrophysics Data System (ADS)

Jójárt, Balázs; Viskolcz, Béla; Poša, Mihalj; Fejer, Szilard N.

2014-04-01

In spite of recent investigations into the potential pharmaceutical importance of bile acids as drug carriers, the structure of bile acid aggregates is largely unknown. Here, we used global optimization techniques to find the lowest energy configurations for clusters composed between 2 and 10 cholate molecules, and evaluated the relative stabilities of the global minima. We found that the energetically most preferred geometries for small aggregates are in fact reverse micellar arrangements, and the classical micellar behaviour (efficient burial of hydrophobic parts) is achieved only in systems containing more than five cholate units. Hydrogen bonding plays a very important part in keeping together the monomers, and among the size range considered, the most stable structure was found to be the decamer, having 17 hydrogen bonds. Molecular dynamics simulations showed that the decamer has the lowest dissociation propensity among the studied aggregation numbers.

Differential evolution-simulated annealing for multiple sequence alignment

NASA Astrophysics Data System (ADS)

Addawe, R. C.; Addawe, J. M.; Sueño, M. R. K.; Magadia, J. C.

2017-10-01

Multiple sequence alignments (MSA) are used in the analysis of molecular evolution and sequence structure relationships. In this paper, a hybrid algorithm, Differential Evolution - Simulated Annealing (DESA) is applied in optimizing multiple sequence alignments (MSAs) based on structural information, non-gaps percentage and totally conserved columns. DESA is a robust algorithm characterized by self-organization, mutation, crossover, and SA-like selection scheme of the strategy parameters. Here, the MSA problem is treated as a multi-objective optimization problem of the hybrid evolutionary algorithm, DESA. Thus, we name the algorithm as DESA-MSA. Simulated sequences and alignments were generated to evaluate the accuracy and efficiency of DESA-MSA using different indel sizes, sequence lengths, deletion rates and insertion rates. The proposed hybrid algorithm obtained acceptable solutions particularly for the MSA problem evaluated based on the three objectives.

Immersive Molecular Visualization with Omnidirectional Stereoscopic Ray Tracing and Remote Rendering

PubMed Central

Stone, John E.; Sherman, William R.; Schulten, Klaus

2016-01-01

Immersive molecular visualization provides the viewer with intuitive perception of complex structures and spatial relationships that are of critical interest to structural biologists. The recent availability of commodity head mounted displays (HMDs) provides a compelling opportunity for widespread adoption of immersive visualization by molecular scientists, but HMDs pose additional challenges due to the need for low-latency, high-frame-rate rendering. State-of-the-art molecular dynamics simulations produce terabytes of data that can be impractical to transfer from remote supercomputers, necessitating routine use of remote visualization. Hardware-accelerated video encoding has profoundly increased frame rates and image resolution for remote visualization, however round-trip network latencies would cause simulator sickness when using HMDs. We present a novel two-phase rendering approach that overcomes network latencies with the combination of omnidirectional stereoscopic progressive ray tracing and high performance rasterization, and its implementation within VMD, a widely used molecular visualization and analysis tool. The new rendering approach enables immersive molecular visualization with rendering techniques such as shadows, ambient occlusion lighting, depth-of-field, and high quality transparency, that are particularly helpful for the study of large biomolecular complexes. We describe ray tracing algorithms that are used to optimize interactivity and quality, and we report key performance metrics of the system. The new techniques can also benefit many other application domains. PMID:27747138

Transitioning NWChem to the Next Generation of Manycore Machines

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

Bylaska, Eric J.; Apra, Edoardo; Kowalski, Karol

The NorthWest Chemistry (NWChem) modeling software is a popular molecular chemistry simulation software that was designed from the start to work on massively parallel processing supercomputers[6, 28, 49]. It contains an umbrella of modules that today includes Self Consistent Field (SCF), second order Mller-Plesset perturbation theory (MP2), Coupled Cluster, multi-conguration selfconsistent eld (MCSCF), selected conguration interaction (CI), tensor contraction engine (TCE) many body methods, density functional theory (DFT), time-dependent density functional theory (TDDFT), real time time-dependent density functional theory, pseudopotential plane-wave density functional theory (PSPW), band structure (BAND), ab initio molecular dynamics, Car-Parrinello molecular dynamics, classical molecular dynamics (MD), QM/MM,more » AIMD/MM, GIAO NMR, COSMO, COSMO-SMD, and RISM solvation models, free energy simulations, reaction path optimization, parallel in time, among other capabilities[ 22]. Moreover new capabilities continue to be added with each new release.« less

Molecular Dynamics Modeling and Simulation of Diamond Cutting of Cerium.

PubMed

Zhang, Junjie; Zheng, Haibing; Shuai, Maobing; Li, Yao; Yang, Yang; Sun, Tao

2017-12-01

The coupling between structural phase transformations and dislocations induces challenges in understanding the deformation behavior of metallic cerium at the nanoscale. In the present work, we elucidate the underlying mechanism of cerium under ultra-precision diamond cutting by means of molecular dynamics modeling and simulations. The molecular dynamics model of diamond cutting of cerium is established by assigning empirical potentials to describe atomic interactions and evaluating properties of two face-centered cubic cerium phases. Subsequent molecular dynamics simulations reveal that dislocation slip dominates the plastic deformation of cerium under the cutting process. In addition, the analysis based on atomic radial distribution functions demonstrates that there are trivial phase transformations from the γ-Ce to the δ-Ce occurred in both machined surface and formed chip. Following investigations on machining parameter dependence reveal the optimal machining conditions for achieving high quality of machined surface of cerium.

Molecular Dynamics Modeling and Simulation of Diamond Cutting of Cerium

NASA Astrophysics Data System (ADS)

Zhang, Junjie; Zheng, Haibing; Shuai, Maobing; Li, Yao; Yang, Yang; Sun, Tao

2017-07-01

The coupling between structural phase transformations and dislocations induces challenges in understanding the deformation behavior of metallic cerium at the nanoscale. In the present work, we elucidate the underlying mechanism of cerium under ultra-precision diamond cutting by means of molecular dynamics modeling and simulations. The molecular dynamics model of diamond cutting of cerium is established by assigning empirical potentials to describe atomic interactions and evaluating properties of two face-centered cubic cerium phases. Subsequent molecular dynamics simulations reveal that dislocation slip dominates the plastic deformation of cerium under the cutting process. In addition, the analysis based on atomic radial distribution functions demonstrates that there are trivial phase transformations from the γ-Ce to the δ-Ce occurred in both machined surface and formed chip. Following investigations on machining parameter dependence reveal the optimal machining conditions for achieving high quality of machined surface of cerium.

Molecular approaches to third generation photovoltaics: photochemical up-conversion

NASA Astrophysics Data System (ADS)

Cheng, Yuen Yap; Fückel, Burkhard; Roberts, Derrick A.; Khoury, Tony; Clady, Rapha"l. G. C. R.; Tayebjee, Murad J. Y.; Piper, Roland; Ekins-Daukes, N. J.; Crossley, Maxwell J.; Schmidt, Timothy W.

2010-08-01

We have investigated a photochemical up-conversion system comprising a molecular mixture of a palladium porphyrin to harvest light, and a polycyclic aromatic hydrocarbon to emit light. The energy of harvested photons is stored as molecular triplet states which then annihilate to bring about up-converted fluorescence. The limiting efficiency of such triplet-triplet annihilation up-conversion has been believed to be 11% for some time. However, by rigorously investigating the kinetics of delayed fluorescence following pulsed excitation, we demonstrate instantaneous annihilation efficiencies exceeding 40%, and limiting efficiencies for the current system of ~60%. We attribute the high efficiencies obtained to the electronic structure of the emitting molecule, which exhibits an exceptionally high T2 molecular state. We utilize the kinetic data obtained to model an up-converting layer irradiated with broadband sunlight, finding that ~3% efficiencies can be obtained with the current system, with this improving dramatically upon optimization of various parameters.

Influence of silver and copper doping on luminescent properties of zinc-phosphate glasses after x-ray irradiation

NASA Astrophysics Data System (ADS)

Murashov, Alexander A.; Sidorov, Alexander I.; Shakhverdov, Teimur A.; Stolyarchuk, Maxim V.

2017-11-01

It is shown, experimentally, that in silver- and copper-containing zinc-phosphate glasses, metal molecular clusters are formed during the glass synthesis. X-ray irradiation of these glasses led to the considerable increase of its luminescence in visible spectral range. This effect is caused by the transformation of the charged metal molecular clusters into the neutral state. Luminescence and excitation spectra of the glass, doped with silver and copper simultaneously, change significantly in comparison with the spectra of glasses doped with one metal. The reason for this can be the formation of hybrid AgnCum molecular clusters. The computer simulation of the structure and optical properties of such clusters by the time-dependent density functional theory method is presented. It is shown that the optimal luminescent material for photonics application, in comparison with other studied materials, is glass, containing hybrid molecular clusters.

Structures in solutions from joint experimental-computational analysis: applications to cyclic molecules and studies of noncovalent interactions.

PubMed

Aliev, Abil E; Mia, Zakirin A; Khaneja, Harmeet S; King, Frank D

2012-01-26

The potential of an approach combining nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations for full structural characterizations in solution is assessed using cyclic organic compounds, namely, benzazocinone derivatives 1-3 with fused five- and eight-membered aliphatic rings, camphoric anhydride 4, and bullvalene 5. Various MD simulations were considered, using force field and semiempirical QM treatments, implicit and explicit solvation, and high-temperature MD calculations for selecting plausible molecular geometries for subsequent QM geometry optimizations using mainly B3LYP, M062X, and MP2 methods. The QM-predicted values of NMR parameters were compared to their experimental values for verification of the final structures derived from the MD/QM analysis. From these comparisons, initial estimates of quality thresholds (calculated as rms deviations) were 0.7-0.9 Hz for (3)J(HH) couplings, 0.07-0.11 Å for interproton distances, 0.05-0.08 ppm for (1)H chemical shifts, and 1.0-2.1 ppm for (13)C chemical shifts. The obtained results suggest that the accuracy of the MD analysis in predicting geometries and relative conformational energies is not critical and that the final geometry refinements of the structures selected from the MD simulations using QM methods are sufficient for correcting for the expected inaccuracy of the MD analysis. A unique example of C(sp(3))-H···N(sp(3)) intramolecular noncovalent interaction is also identified using the NMR/MD/QM and the natural bond orbital analyses. As the NMR/MD/QM approach relies on the final QM geometry optimization, comparisons of geometric characteristics predicted by different QM methods and those from X-ray and neutron diffraction measurements were undertaken using rigid and flexible cyclic systems. The joint analysis shows that intermolecular noncovalent interactions present in the solid state alter molecular geometries significantly compared to the geometries of isolated molecules from QM calculations.

LAMBADA and InflateGRO2: efficient membrane alignment and insertion of membrane proteins for molecular dynamics simulations.

PubMed

Schmidt, Thomas H; Kandt, Christian

2012-10-22

At the beginning of each molecular dynamics membrane simulation stands the generation of a suitable starting structure which includes the working steps of aligning membrane and protein and seamlessly accommodating the protein in the membrane. Here we introduce two efficient and complementary methods based on pre-equilibrated membrane patches, automating these steps. Using a voxel-based cast of the coarse-grained protein, LAMBADA computes a hydrophilicity profile-derived scoring function based on which the optimal rotation and translation operations are determined to align protein and membrane. Employing an entirely geometrical approach, LAMBADA is independent from any precalculated data and aligns even large membrane proteins within minutes on a regular workstation. LAMBADA is the first tool performing the entire alignment process automatically while providing the user with the explicit 3D coordinates of the aligned protein and membrane. The second tool is an extension of the InflateGRO method addressing the shortcomings of its predecessor in a fully automated workflow. Determining the exact number of overlapping lipids based on the area occupied by the protein and restricting expansion, compression and energy minimization steps to a subset of relevant lipids through automatically calculated and system-optimized operation parameters, InflateGRO2 yields optimal lipid packing and reduces lipid vacuum exposure to a minimum preserving as much of the equilibrated membrane structure as possible. Applicable to atomistic and coarse grain structures in MARTINI format, InflateGRO2 offers high accuracy, fast performance, and increased application flexibility permitting the easy preparation of systems exhibiting heterogeneous lipid composition as well as embedding proteins into multiple membranes. Both tools can be used separately, in combination with other methods, or in tandem permitting a fully automated workflow while retaining a maximum level of usage control and flexibility. To assess the performance of both methods, we carried out test runs using 22 membrane proteins of different size and transmembrane structure.

Molecular structure, FT-IR, FT-Raman, NBO, HOMO and LUMO, MEP, NLO and molecular docking study of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid.

PubMed

Ulahannan, Rajeev T; Panicker, C Yohannan; Varghese, Hema Tresa; Musiol, Robert; Jampilek, Josef; Van Alsenoy, Christian; War, Javeed Ahmad; Srivastava, S K

2015-01-01

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of the normal modes of vibrations was done using GAR2PED program. (1)H NMR chemical shifts calculations were carried out by using B3LYP functional with SDD basis set. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. MEP was performed by the DFT method and the predicted infrared intensities and Raman activities have also been reported. The calculated geometrical parameters are in agreement with that of similar derivatives. The title compound forms a stable complex with PknB as is evident from the binding affinity values and the molecular docking results suggest that the compound might exhibit inhibitory activity against PknB and this may result in development of new anti-tuberculostic agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs.

PubMed

Krall, Jacob; Jensen, Claus Hatt; Bavo, Francesco; Falk-Petersen, Christina Birkedahl; Haugaard, Anne Stæhr; Vogensen, Stine Byskov; Tian, Yongsong; Nittegaard-Nielsen, Mia; Sigurdardóttir, Sara Björk; Kehler, Jan; Kongstad, Kenneth Thermann; Gloriam, David E; Clausen, Rasmus Prætorius; Harpsøe, Kasper; Wellendorph, Petrine; Frølund, Bente

2017-11-09

γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar K i ) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.

Inferences from structural comparison: flexibility, secondary structure wobble and sequence alignment optimization.

PubMed

Zhang, Gaihua; Su, Zhen

2012-01-01

Work on protein structure prediction is very useful in biological research. To evaluate their accuracy, experimental protein structures or their derived data are used as the 'gold standard'. However, as proteins are dynamic molecular machines with structural flexibility such a standard may be unreliable. To investigate the influence of the structure flexibility, we analysed 3,652 protein structures of 137 unique sequences from 24 protein families. The results showed that (1) the three-dimensional (3D) protein structures were not rigid: the root-mean-square deviation (RMSD) of the backbone Cα of structures with identical sequences was relatively large, with the average of the maximum RMSD from each of the 137 sequences being 1.06 Å; (2) the derived data of the 3D structure was not constant, e.g. the highest ratio of the secondary structure wobble site was 60.69%, with the sequence alignments from structural comparisons of two proteins in the same family sometimes being completely different. Proteins may have several stable conformations and the data derived from resolved structures as a 'gold standard' should be optimized before being utilized as criteria to evaluate the prediction methods, e.g. sequence alignment from structural comparison. Helix/β-sheet transition exists in normal free proteins. The coil ratio of the 3D structure could affect its resolution as determined by X-ray crystallography.

Spectral investigations, DFT computations and molecular docking studies of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(2-methylphenyl)piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione

NASA Astrophysics Data System (ADS)

Resmi, K. S.; Mary, Y. Sheena; Varghese, Hema Tresa; Panicker, C. Yohannan; Pakosińska-Parys, Magdalena; Alsenoy, C. Van

2015-10-01

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of the title compound have been investigated experimentally and theoretically. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analysed using NBO analysis. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against human M2 muscarinic acetylcholine receptor.

Artificial Hip Simulator with Crystal Models

NASA Image and Video Library

1966-06-21

Robert Johnson, top, sets the lubricant flow while Donald Buckley adjusts the bearing specimen on an artificial hip simulator at the National Aeronautics and Space Administration (NASA) Lewis Research Center. The simulator was supplemented by large crystal lattice models to demonstrate the composition of different bearing alloys. This this image by NASA photographer Paul Riedel was used for the cover of the August 15, 1966 edition of McGraw-Hill Product Engineering. Johnson was chief of Lubrication Branch and Buckley head of the Space Environment Lubrication Section in the Fluid System Components Division. In 1962 they began studying the molecular structure of metals. Their friction and wear testing revealed that the optimal structure for metal bearings was a hexagonal crystal structure with proper molecular space. Bearing manufacturers traditionally preferred cubic structures over hexagonal arrangements. Buckley and Johnson found that even though the hexagonal structural was not as inherently strong as its cubic counterpart, it was less likely to cause a catastrophic failure. The Lewis researchers concentrated their efforts on cobalt-molybdenum and titanium alloys for high temperatures applications. The alloys had a number of possible uses, included prosthetics. The alloys were similar in composition to the commercial alloys used for prosthetics, but employed the longer lasting hexagonal structure.

Structural, spectroscopic and DFT study of 4-methoxybenzohydrazide Schiff bases. A new series of polyfunctional ligands.

PubMed

Ferraresi-Curotto, Verónica; Echeverría, Gustavo A; Piro, Oscar E; Pis-Diez, Reinaldo; González-Baró, Ana C

2015-02-25

Five Schiff bases obtained from condensation of 4-methoxybenzohydrazide with related aldehydes, namely o-vanillin, vanillin, 5-bromovanillin, 5-chlorosalicylaldehyde and 5-bromosalicylaldehyde were prepared. A detailed structural and spectroscopic study is reported. The crystal structures of four members of the family were determined and compared with one another. The hydrazones obtained from 5-chlorosalicylaldehyde and 5-bromosalicylaldehyde resulted to be isomorphic to each other. The solid-state structures are stabilized by intra-molecular O-H⋯N interactions in salicylaldehyde derivatives between the O-H moiety from the aldehyde and the hydrazone nitrogen atom. All crystals are further stabilized by inter-molecular H-bonds mediated by the crystallization water molecule. A comparative analysis between experimental and theoretical results is presented. The conformational space was searched and geometries were optimized both in gas phase and including solvent effects. The structure is predicted for the compound for which the crystal structure was not determined. Infrared and electronic spectra were measured and assigned with the help of data obtained from computational methods based on the Density Functional Theory. Copyright © 2014 Elsevier B.V. All rights reserved.

Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors.

PubMed

Choi, Jun Yong; Fuerst, Rita; Knapinska, Anna M; Taylor, Alexander B; Smith, Lyndsay; Cao, Xiaohang; Hart, P John; Fields, Gregg B; Roush, William R

2017-07-13

We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13·inhibitor complexes followed by molecular design and synthesis of potent but nonselective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn 2+ chelating unit was replaced with nonchelating polar residues that bridged over the Zn 2+ binding site and reached into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors 10d and (S)-17b, which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn 2+ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs.

Optimized multi-step NMR-crystallography approach for structural characterization of a stable quercetin solvate.

PubMed

Filip, Xenia; Miclaus, Maria; Martin, Flavia; Filip, Claudiu; Grosu, Ioana Georgeta

2017-05-10

Herein we report the preparation and solid state structural investigation of the 1,4-dioxane-quercetin solvate. NMR crystallography methods were employed for crystal structure determination of the solvate from microcrystalline powder. The stability of the compound relative to other reported quercetin solvates is discussed and found to be in perfect agreement with the hydrogen bonding networks/supra-molecular architectures formed in each case. It is also clearly shown that NMR crystallography represents an ideal analytical tool in such cases when hydrogen-bonding networks are required to be constrained at a high accuracy level. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis, geometry optimization, spectroscopic investigations (UV/Vis, excited states, FT-IR) and application of new azomethine dyes

NASA Astrophysics Data System (ADS)

Shahab, Siyamak; Sheikhi, Masoome; Filippovich, Liudmila; Kumar, Rakesh; Dikusar, Evgenij; Yahyaei, Hooriye; Khaleghian, Mehrnoosh

2017-11-01

In the present work, the quantum theoretical calculations of the molecular structures of the four new synthesized azomethine dyes such as: (E)-N-(4-butoxybenzylidene)-4-((E)-phenyldiazenyl)aniline (PAZB-6), (E)-N-(4-(benzyloxy)benzylidene)-4-((E))-phenyldiazenyl)aniline (PAZB-7), 4-((E)-4-((E)-phenyldiazenyl)phenyl)imino)methyl)phenol (PAZB-8), (E)-N-(4-methoxybenzylidene)-4-((E))-phenyldiazenyl)aniline (PAZB-9) have been predicted using Density Functional Theory in the solvent Dimethylformamide. The geometries of the azomethine dyes were optimized by PBE1PBE/6-31+G* level of theory. The electronic spectra of the title compounds in the solvent DMF was carried out by TDPBE1PBE/6-31+G* method. FT-IR spectra of the title compounds are recorded and discussed. Frontier molecular orbitals, molecular electrostatic potential, electronic properties, natural charges and Natural Bond Orbital (NBO) analysis of the mentioned compounds were investigated and discussed by theoretical calculations. The azomethine dyes were synthesized after quantum chemical modeling for optical applications. A new study of anisotropy of thermal and electrical conductivity of the colored stretched PVA-films have been undertaken.

Profiling the interaction mechanism of quinoline/quinazoline derivatives as MCHR1 antagonists: an in silico method.

PubMed

Wu, Mingwei; Li, Yan; Fu, Xinmei; Wang, Jinghui; Zhang, Shuwei; Yang, Ling

2014-09-01

Melanin concentrating hormone receptor 1 (MCHR1), a crucial regulator of energy homeostasis involved in the control of feeding and energy metabolism, is a promising target for treatment of obesity. In the present work, the up-to-date largest set of 181 quinoline/quinazoline derivatives as MCHR1 antagonists was subjected to both ligand- and receptor-based three-dimensional quantitative structure-activity (3D-QSAR) analysis applying comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The optimal predictable CoMSIA model exhibited significant validity with the cross-validated correlation coefficient (Q²) = 0.509, non-cross-validated correlation coefficient (R²(ncv)) = 0.841 and the predicted correlation coefficient (R²(pred)) = 0.745. In addition, docking studies and molecular dynamics (MD) simulations were carried out for further elucidation of the binding modes of MCHR1 antagonists. MD simulations in both water and lipid bilayer systems were performed. We hope that the obtained models and information may help to provide an insight into the interaction mechanism of MCHR1 antagonists and facilitate the design and optimization of novel antagonists as anti-obesity agents.

From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins.

PubMed

Verdes, Aida; Anand, Prachi; Gorson, Juliette; Jannetti, Stephen; Kelly, Patrick; Leffler, Abba; Simpson, Danny; Ramrattan, Girish; Holford, Mandë

2016-04-19

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.

Experimental and theoretical studies on vibrational spectra of 4-(2-furanylmethyleneamino)antipyrine, 4-benzylideneaminoantipyrine and 4-cinnamilideneaminoantipyrine

NASA Astrophysics Data System (ADS)

Sun, Yu-Xi; Hao, Qing-Li; Yu, Zong-Xue; Jiang, Wen-Jun; Lu, Lu-De; Wang, Xin

2009-09-01

This work deals with the IR and Raman spectroscopy of 4-(2-furanylmethyleneamino) antipyrine (FAP), 4-benzylideneaminoantipyrine (BAP) and 4-cinnamilideneaminoantipyrine (CAP) by means of experimental and quantum chemical calculations. The equilibrium geometries, harmonic frequencies, infrared intensities and Raman scattering activities were calculated by density functional B3LYP method with the 6-31G(d) basis set. The comparisons between the calculated and experimental results covering molecular structures, assignments of fundamental vibrational modes and thermodynamic properties were investigated. The optimized molecular geometries have been compared with the experimental data obtained from XRD data, which indicates that the theoretical results agree well with the corresponding experimental values. For the three compounds, comparisons and assignments of the vibrational frequencies indicate that the calculated frequencies are close to the experimental data, and the IR spectra are comparable with some slight differences, whereas the Raman spectra are different clearly and the strongest Raman scattering actives are relative tightly to the molecular conjugative moieties linked through their Schiff base imines. The thermodynamic properties (heat capacities, entropies and enthalpy changes) and their correlations with temperatures were also obtained from the harmonic frequencies of the optimized strucutres.

A structural study of fentanyl by DFT calculations, NMR and IR spectroscopy

NASA Astrophysics Data System (ADS)

Asadi, Zahra; Esrafili, Mehdi D.; Vessally, Esmail; Asnaashariisfahani, Manzarbanou; Yahyaei, Saeideh; Khani, Ali

2017-01-01

N-(1-(2-phenethyl)-4-piperidinyl-N-phenyl-propanamide (fentanyl) is synthesized and characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The geometry optimization is performed using the B3LYP and M06 density functionals with 6-311 + G(d) and 6-311++G(d,p) basis sets. The complete assignments are performed on the basis of the potential energy distribution (PED) of the all vibrational modes. Almost a nice correlation is found between the calculated 13C chemical shifts and experimental data. The frontier molecular orbitals and molecular electrostatic potential of fentanyl are also obtained.

Discovery of CREBBP Bromodomain Inhibitors by High-Throughput Docking and Hit Optimization Guided by Molecular Dynamics.

PubMed

Xu, Min; Unzue, Andrea; Dong, Jing; Spiliotopoulos, Dimitrios; Nevado, Cristina; Caflisch, Amedeo

2016-02-25

We have identified two chemotypes of CREBBP bromodomain ligands by fragment-based high-throughput docking. Only 17 molecules from the original library of two-million compounds were tested in vitro. Optimization of the two low-micromolar hits, the 4-acylpyrrole 1 and acylbenzene 9, was driven by molecular dynamics results which suggested improvement of the polar interactions with the Arg1173 side chain at the rim of the binding site. The synthesis of only two derivatives of 1 yielded the 4-acylpyrrole 6 which shows a single-digit micromolar affinity for the CREBBP bromodomain and a ligand efficiency of 0.34 kcal/mol per non-hydrogen atom. Optimization of the acylbenzene hit 9 resulted in a series of derivatives with nanomolar potencies, good ligand efficiency and selectivity (see Unzue, A.; Xu, M.; Dong, J.; Wiedmer, L.; Spiliotopoulos, D.; Caflisch, A.; Nevado, C.Fragment-Based Design of Selective Nanomolar Ligands of the CREBBP Bromodomain. J. Med. Chem. 2015, DOI: 10.1021/acs.jmedchem.5b00172). The in silico predicted binding mode of the acylbenzene derivative 10 was validated by solving the structure of the complex with the CREBBP bromodomain.

ProSelection: A Novel Algorithm to Select Proper Protein Structure Subsets for in Silico Target Identification and Drug Discovery Research.

PubMed

Wang, Nanyi; Wang, Lirong; Xie, Xiang-Qun

2017-11-27

Molecular docking is widely applied to computer-aided drug design and has become relatively mature in the recent decades. Application of docking in modeling varies from single lead compound optimization to large-scale virtual screening. The performance of molecular docking is highly dependent on the protein structures selected. It is especially challenging for large-scale target prediction research when multiple structures are available for a single target. Therefore, we have established ProSelection, a docking preferred-protein selection algorithm, in order to generate the proper structure subset(s). By the ProSelection algorithm, protein structures of "weak selectors" are filtered out whereas structures of "strong selectors" are kept. Specifically, the structure which has a good statistical performance of distinguishing active ligands from inactive ligands is defined as a strong selector. In this study, 249 protein structures of 14 autophagy-related targets are investigated. Surflex-dock was used as the docking engine to distinguish active and inactive compounds against these protein structures. Both t test and Mann-Whitney U test were used to distinguish the strong from the weak selectors based on the normality of the docking score distribution. The suggested docking score threshold for active ligands (SDA) was generated for each strong selector structure according to the receiver operating characteristic (ROC) curve. The performance of ProSelection was further validated by predicting the potential off-targets of 43 U.S. Federal Drug Administration approved small molecule antineoplastic drugs. Overall, ProSelection will accelerate the computational work in protein structure selection and could be a useful tool for molecular docking, target prediction, and protein-chemical database establishment research.

Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

PubMed

Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

2016-01-15

Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transition-state optimization by the free energy gradient method: Application to aqueous-phase Menshutkin reaction between ammonia and methyl chloride

NASA Astrophysics Data System (ADS)

Hirao, Hajime; Nagae, Yukihiko; Nagaoka, Masataka

2001-11-01

The transition state (TS) for the Menshutkin reaction H 3N+CH 3Cl→H 3NCH 3++Cl - in aqueous solution was located on the free energy surface (FES) by the free energy gradient (FEG) method. The solute-solvent system was described by a hybrid quantum mechanical and molecular mechanical (QM/MM) method. The reaction path in water was found to deviate largely from that in the gas phase. It was concluded that, in such a reaction including charge separation, TS structure optimization on an FES is inevitable for obtaining valid information about a TS in solution.

Controlling Molecular Ordering in Solution-State Conjugated Polymers

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

Zhu, Jiahua; Han, Youngkyu; Kumar, Rajeev

Rationally encoding molecular interactions that can control the assembly structure and functional expression in solution of conjugated polymers holds great potential for enabling optimal organic optoelectronic and sensory materials. In this work, we show that thermally-controlled and surfactant-guided assembly of water-soluble conjugated polymers in aqueous solution is a simple and effective strategy to generate optoelectronic materials with desired molecular ordering. We have studied a conjugated polymer consisting of a hydrophobic thiophene backbone and hydrophilic, thermo-responsive ethylene oxide side groups, which shows a step-wise, multi-dimensional assembly in water. By incorporating the polymer into phase-segregated domains of an amphiphilic surfactant in solution,more » we demonstrate that both chain conformation and degree of molecular ordering of the conjugated polymer can be tuned in hexagonal, micellar and lamellar phases of the surfactant solution. The controlled molecular ordering in conjugated polymer assembly is demonstrated as a key factor determining the electronic interaction and optical function.« less

Controlling Molecular Ordering in Solution-State Conjugated Polymers

DOE PAGES

Zhu, Jiahua; Han, Youngkyu; Kumar, Rajeev; ...

2015-07-17

Rationally encoding molecular interactions that can control the assembly structure and functional expression in solution of conjugated polymers holds great potential for enabling optimal organic optoelectronic and sensory materials. In this work, we show that thermally-controlled and surfactant-guided assembly of water-soluble conjugated polymers in aqueous solution is a simple and effective strategy to generate optoelectronic materials with desired molecular ordering. We have studied a conjugated polymer consisting of a hydrophobic thiophene backbone and hydrophilic, thermo-responsive ethylene oxide side groups, which shows a step-wise, multi-dimensional assembly in water. By incorporating the polymer into phase-segregated domains of an amphiphilic surfactant in solution,more » we demonstrate that both chain conformation and degree of molecular ordering of the conjugated polymer can be tuned in hexagonal, micellar and lamellar phases of the surfactant solution. The controlled molecular ordering in conjugated polymer assembly is demonstrated as a key factor determining the electronic interaction and optical function.« less

Titan's organic aerosols: Molecular composition and structure of laboratory analogues inferred from pyrolysis gas chromatography mass spectrometry analysis

NASA Astrophysics Data System (ADS)

Morisson, Marietta; Szopa, Cyril; Carrasco, Nathalie; Buch, Arnaud; Gautier, Thomas

2016-10-01

Analogues of Titan's aerosols are of primary interest in the understanding of Titan's atmospheric chemistry and climate, and in the development of in situ instrumentation for future space missions. Numerous studies have been carried out to characterize laboratory analogues of Titan aerosols (tholins), but their molecular composition and structure are still poorly known. If pyrolysis gas chromatography mass spectrometry (pyr-GCMS) has been used for years to give clues about their chemical composition, highly disparate results were obtained with this technique. They can be attributed to the variety of analytical conditions used for pyr-GCMS analyses, and/or to differences in the nature of the analogues analyzed, that were produced with different laboratory set-ups under various operating conditions. In order to have a better description of Titan's tholin's molecular composition by pyr-GCMS, we carried out a systematic study with two major objectives: (i) exploring the pyr-GCMS analytical parameters to find the optimal ones for the detection of a wide range of chemical products allowing a characterization of the tholins composition as comprehensive as possible, and (ii) highlighting the role of the CH4 ratio in the gaseous reactive medium on the tholin's molecular structure. We used a radio-frequency plasma discharge to synthetize tholins with different concentrations of CH4 diluted in N2. The samples were pyrolyzed at temperatures covering the 200-700°C range. The extracted gases were then analyzed by GCMS for their molecular identification. The optimal pyrolysis temperature for characterizing the molecular composition of our tholins by GCMS analysis is found to be 600°C. This temperature choice results from the best compromise between the number of compounds released, the quality of the signal and the appearance of pyrolysis artifacts. About a hundred molecules are identified as pyrolysates. A common major chromatographic pattern appears clearly for all the samples even if the number of released compounds can significantly differ. The hydrocarbon chain content increases in tholins when the CH4 ratio increases. A semi-quantitative study of the nitriles (most abundant chemical family in our chromatograms) released during the pyrolysis shows the existence of a correlation between the amount of a nitrile released and its molecular mass, similarly to the previous quantification of nitriles in the plasma gas-phase. Moreover, numerous nitriles are present both in tholins and in the gas phase, confirming their suspected role in the gas phase as precursors of the solid organic particles.

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

Vijayakumar, M.; Nie, Zimin; Walter, Eric D.

Redox flow battery (RFB) is a promising candidate for energy storage component in designing resilient grid scale power supply due to the advantage of the separation of power and energy. However, poorly understood chemical and thermal stability issues of electrolytes currently limit the performance of RFB. Designing of high performance stable electrolytes requires comprehensive knowledge about the molecular level solvation structure and dynamics of their redox active species. The molecular level understanding of detrimental V2O5 precipitation process led to successful designing of mixed acid based electrolytes for vanadium redox flow batteries (VRFB). The higher stability of mixed acid based electrolytesmore » is attributed to the choice of hydrochloric acid as optimal co-solvent, which provides chloride anions for ligand exchange process in vanadium solvation structure. The role of chloride counter anion on solvation structure and dynamics of vanadium species were studied using combined magnetic resonance spectroscopy and DFT based theoretical methods. Finally, the solvation phenomenon of multiple vanadium species and their impact on VRFB electrolyte chemical stability were discussed.« less

Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis

PubMed Central

Barnwal, Ravi Pratap; Loh, Edmund; Godin, Katherine S.; Yip, Jordan; Lavender, Hayley; Tang, Christoph M.; Varani, Gabriele

2016-01-01

Neisseria meningitidis causes bacterial meningitis and septicemia. It evades the host complement system by upregulating expression of immune evasion factors in response to changes in temperature. RNA thermometers within mRNAs control expression of bacterial immune evasion factors, including CssA, in the 5′-untranslated region of the operon for capsule biosynthesis. We dissect the molecular mechanisms of thermoregulation and report the structure of the CssA thermometer. We show that the RNA thermometer acts as a rheostat, whose stability is optimized to respond in a small temperature range around 37°C as occur within the upper airways during infection. Small increases in temperature gradually open up the structure to allow progressively increased access to the ribosome binding site. Even small changes in stability induced by mutations of imperfect base pairs, as in naturally occurring polymorphisms, shift the thermometer response outside of the desired temperature range, suggesting that its activity could be modulated by pharmacological intervention. PMID:27369378

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

Ghosh, Arun K.; Takayama, Jun; Rao, Kalapala Venkateswar

The design, synthesis, X-ray crystal structure, molecular modeling, and biological evaluation of a series of new generation SARS-CoV PLpro inhibitors are described. A new lead compound 3 (6577871) was identified via high-throughput screening of a diverse chemical library. Subsequently, we carried out lead optimization and structure-activity studies to provide a series of improved inhibitors that show potent PLpro inhibition and antiviral activity against SARS-CoV infected Vero E6 cells. Interestingly, the (S)-Me inhibitor 15h (enzyme IC{sub 50} = 0.56 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) and the corresponding (R)-Me 15g (IC{sub 50} = 0.32 {mu}M; antiviral EC{sub 50} = 9.1more » {mu}M) are the most potent compounds in this series, with nearly equivalent enzymatic inhibition and antiviral activity. A protein-ligand X-ray structure of 15g-bound SARS-CoV PLpro and a corresponding model of 15h docked to PLpro provide intriguing molecular insight into the ligand-binding site interactions.« less

Elucidating Solvation Structures for Rational Design of Multivalent Electrolytes-A Review.

PubMed

Rajput, Nav Nidhi; Seguin, Trevor J; Wood, Brandon M; Qu, Xiaohui; Persson, Kristin A

2018-04-26

Fundamental molecular-level understanding of functional properties of liquid solutions provides an important basis for designing optimized electrolytes for numerous applications. In particular, exhaustive knowledge of solvation structure, stability, and transport properties is critical for developing stable electrolytes for fast-charging and high-energy-density next-generation energy storage systems. Accordingly, there is growing interest in the rational design of electrolytes for beyond lithium-ion systems by tuning the molecular-level interactions of solvate species present in the electrolytes. Here we present a review of the solvation structure of multivalent electrolytes and its impact on the electrochemical performance of these batteries. A direct correlation between solvate species present in the solution and macroscopic properties of electrolytes is sparse for multivalent electrolytes and contradictory results have been reported in the literature. This review aims to illustrate the current understanding, compare results, and highlight future needs and directions to enable the deep understanding needed for the rational design of improved multivalent electrolytes.

Structural insight into molecular mechanism of poly(ethylene terephthalate) degradation.

PubMed

Joo, Seongjoon; Cho, In Jin; Seo, Hogyun; Son, Hyeoncheol Francis; Sagong, Hye-Young; Shin, Tae Joo; Choi, So Young; Lee, Sang Yup; Kim, Kyung-Jin

2018-01-26

Plastics, including poly(ethylene terephthalate) (PET), possess many desirable characteristics and thus are widely used in daily life. However, non-biodegradability, once thought to be an advantage offered by plastics, is causing major environmental problem. Recently, a PET-degrading bacterium, Ideonella sakaiensis, was identified and suggested for possible use in degradation and/or recycling of PET. However, the molecular mechanism of PET degradation is not known. Here we report the crystal structure of I. sakaiensis PETase (IsPETase) at 1.5 Å resolution. IsPETase has a Ser-His-Asp catalytic triad at its active site and contains an optimal substrate binding site to accommodate four monohydroxyethyl terephthalate (MHET) moieties of PET. Based on structural and site-directed mutagenesis experiments, the detailed process of PET degradation into MHET, terephthalic acid, and ethylene glycol is suggested. Moreover, other PETase candidates potentially having high PET-degrading activities are suggested based on phylogenetic tree analysis of 69 PETase-like proteins.

A ligand-directed divergent catalytic approach to establish structural and functional scaffold diversity

NASA Astrophysics Data System (ADS)

Lee, Yen-Chun; Patil, Sumersing; Golz, Christopher; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert

2017-02-01

The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands. Herein we present a ligand-directed synthesis approach for the gold(I)-catalysed cycloisomerization of oxindole-derived 1,6-enynes that affords distinct molecular scaffolds following different catalytic reaction pathways. Varying electronic properties and the steric demand of the gold(I) ligands steers the fate of a common intermediary gold carbene to selectively form spirooxindoles, quinolones or df-oxindoles. Investigation of a synthesized compound collection in cell-based assays delivers structurally novel, selective modulators of the Hedgehog and Wnt signalling pathways, autophagy and of cellular proliferation.

Interfacial assignment of branched-alkyl benzene sulfonates: A molecular simulation

NASA Astrophysics Data System (ADS)

Liu, Zi-Yu; Wei, Ning; Wang, Ce; Zhou, He; Zhang, Lei; Liao, Qi; Zhang, Lu

2015-11-01

A molecular dynamics simulation was conducted to analyze orientations of sodium branched-alkyl benzene sulfonates molecules at nonane/water interface, which is helpful to design optimal surfactant structures to achieve ultralow interfacial tension (IFT). Through the two dimensional density profiles, monolayer collapses are found when surfactant concentration continues to increase. Thus the precise scope of monolayer is certain and orientation can be analyzed. Based on the simulated results, we verdict the interfacial assignment of branched-alkyl benzene sulfonates at the oil-water interface, and discuss the effect of hydrophobic tail structure on surfactant assignment. Bigger hydrophobic size can slow the change rate of surfactant occupied area as steric hindrance, and surfactant meta hydrophobic tails have a stronger tendency to stretch to the oil phase below the collapsed concentration. Furthermore, an interfacial model with reference to collapse, increasing steric hindrance and charge repulsive force between interfacial surfactant molecules, responsible for effecting of surfactant concentration and structure has been supposed.

Synthesis, spectral characterization and X-ray crystal structure studies of 3-(benzo[d][1,3]dioxol-5-yl)-5-(3-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carboxamide: Hirshfeld surface, DFT and thermal analysis

NASA Astrophysics Data System (ADS)

Kumara, Karthik; Dileep Kumar, A.; Naveen, S.; Ajay Kumar, K.; Lokanath, N. K.

2018-06-01

A novel pyrazole derivative, 3-(benzo[d][1,3]dioxol-5-yl)-5-(3-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carboxamide was synthesized and characterized by elemental analysis, FT-IR, NMR (1H and 13C), MS, UV-visible spectra and finally the structure was confirmed by the single crystal X-ray diffraction studies. The title compound (C16H15N3O3S) crystallized in the triclinic crystal system, with the space group Pī. A dihedral angle of 65.84(1)° between the pyrazole and the thiophene rings confirms the twisted conformation between them. The X-ray structure revealed that the pyrazole ring adopts an E-form and an envelope conformation on C7 atom. The crystal and molecular structure of the title compound is stabilized by inter molecular hydrogen bonds. The compound possesses three dimensional supramolecular self-assembly, in which Csbnd H⋯O and Nsbnd H⋯O chains build up two dimensional arrays, which are extended to 3D network through Csbnd H···Cg and Csbnd O···Cg interactions. The structure also exhibits intramolecular hydrogen bonds of the type Nsbnd H⋯N and π···π stacking interactions, which contributes to the crystal packing. Further, Hirshfeld surface analysis was carried out for the graphical visualization of several short intermolecular interactions on the molecular surface while the 2D finger-print plot provides percentage contribution of each individual atom-to-atom interactions. The thermal decomposition of the compound has been studied by thermogravimetric analysis. The molecular geometries and electronic structures of the compounds were fully optimized, calculated with ab-initio methods by HF, DFT/B3LYP functional in combination of different basis set with different solvent environment and the structural parameters were compared with the experimental data. The Mulliken atomic charges and molecular electrostatic potential on molecular van der Waals (vdW) surface were calculated to know the electrophilic and nucleophilic regions of the molecular surface. Nonlinear optical properties of the title compound were also discussed based on the polarizability and hyperpolarizability values.

Efficiency bounds of molecular motors under a trade-off figure of merit

NASA Astrophysics Data System (ADS)

Zhang, Yanchao; Huang, Chuankun; Lin, Guoxing; Chen, Jincan

2017-05-01

On the basis of the theory of irreversible thermodynamics and an elementary model of the molecular motors converting chemical energy by ATP hydrolysis to mechanical work exerted against an external force, the efficiencies of the molecular motors at two different optimization configurations for trade-off figure of merit representing a best compromise between the useful energy and the lost energy are calculated. The upper and lower bounds for the efficiency at two different optimization configurations are determined. It is found that the optimal efficiencies at the two different optimization configurations are always larger than 1 / 2.

Ab initio random structure searching of organic molecular solids: assessment and validation against experimental data† †Electronic supplementary information (ESI) available: Results of similarity analysis between the 11 structures of lowest energy obtained in the AIRSS calculations and the reported structures of form III and form IV of m-ABA; unit cell parameters and volumes for all structures considered; comparison of 2θ values derived from the unit cell parameters of different structural models representing form III of m-ABA; Le Bail fitting of the experimental powder XRD pattern of form IV of m-ABA recorded at 70 K using, as the initial structural model, the reported crystal structure following geometry optimization; table of calculated (GIPAW) absolute isotropic NMR shieldings; simulated powder XRD data for the considered structures after precise geometry optimization; experimental 1H MAS NMR spectra of forms III and IV. (pdf) The calculated and experimental data for this study are provided as a supporting dataset from WRAP, the Warwick Research Archive Portal at http://wrap.warwick.ac.uk/91884. See DOI: 10.1039/c7cp04186a

PubMed Central

Zilka, Miri; Dudenko, Dmytro V.; Hughes, Colan E.; Williams, P. Andrew; Sturniolo, Simone; Franks, W. Trent; Pickard, Chris J.

2017-01-01

This paper explores the capability of using the DFT-D ab initio random structure searching (AIRSS) method to generate crystal structures of organic molecular materials, focusing on a system (m-aminobenzoic acid; m-ABA) that is known from experimental studies to exhibit abundant polymorphism. Within the structural constraints selected for the AIRSS calculations (specifically, centrosymmetric structures with Z = 4 for zwitterionic m-ABA molecules), the method is shown to successfully generate the two known polymorphs of m-ABA (form III and form IV) that have these structural features. We highlight various issues that are encountered in comparing crystal structures generated by AIRSS to experimental powder X-ray diffraction (XRD) data and solid-state magic-angle spinning (MAS) NMR data, demonstrating successful fitting for some of the lowest energy structures from the AIRSS calculations against experimental low-temperature powder XRD data for known polymorphs of m-ABA, and showing that comparison of computed and experimental solid-state NMR parameters allows different hydrogen-bonding motifs to be discriminated. PMID:28944393

Investigation of solvent polarity effect on molecular structure and vibrational spectrum of xanthine with the aid of quantum chemical computations.

PubMed

Polat, Turgay; Yıldırım, Gurcan

2014-04-05

The main scope of this study is to determine the effects of 8 solvents on the geometric structure and vibrational spectra of the title compound, xanthine, by means of the DFT/B3LYP level of theory in the combination with the polarizable conductor continuum model (CPCM) for the first time. After determination of the most-steady state (favored structure) of the xanthine molecule, the role of the solvent polarity on the SCF energy (for the molecule stability), atomic charges (for charge distribution) and dipole moments (for molecular charge transfer) belonging to tautomer is discussed in detail. The results obtained indicate not only the presence of the hydrogen bonding and strong intra-molecular charge transfer (ICT) in the compound but the increment of the molecule stability with the solvent polarity, as well. Moreover, it is noted that the optimized geometric parameters and the theoretical vibrational frequencies are in good agreement with the available experimental results found in the literature. In fact, the correlations between the experimental and theoretical findings for the molecular structures improve with the enhancement of the solvent polarity. At the same time, the dimer forms of the xanthine compound are simulated to describe the effect of intermolecular hydrogen bonding on the molecular geometry and vibrational frequencies. It is found that the CO and NH stretching vibrations shift regularly to lower frequency value with higher IR intensity as the dielectric medium enhances systematically due to the intermolecular NH⋯O hydrogen bonds. Theoretical vibrational spectra are also assigned based on the potential energy distribution (PED) using the VEDA 4 program. Copyright © 2013 Elsevier B.V. All rights reserved.

An automated method to find transition states using chemical dynamics simulations.

PubMed

Martínez-Núñez, Emilio

2015-02-05

A procedure to automatically find the transition states (TSs) of a molecular system (MS) is proposed. It has two components: high-energy chemical dynamics simulations (CDS), and an algorithm that analyzes the geometries along the trajectories to find reactive pathways. Two levels of electronic structure calculations are involved: a low level (LL) is used to integrate the trajectories and also to optimize the TSs, and a higher level (HL) is used to reoptimize the structures. The method has been tested in three MSs: formaldehyde, formic acid (FA), and vinyl cyanide (VC), using MOPAC2012 and Gaussian09 to run the LL and HL calculations, respectively. Both the efficacy and efficiency of the method are very good, with around 15 TS structures optimized every 10 trajectories, which gives a total of 7, 12, and 83 TSs for formaldehyde, FA, and VC, respectively. The use of CDS makes it a powerful tool to unveil possible nonstatistical behavior of the system under study. © 2014 Wiley Periodicals, Inc.

Immbolization of uricase enzyme in Langmuir and Langmuir-Blodgett films of fatty acids: possible use as a uric acid sensor.

PubMed

Zanon, Nathaly C M; Oliveira, Osvaldo N; Caseli, Luciano

2012-05-01

Preserving the enzyme structure in solid films is key for producing various bioelectronic devices, including biosensors, which has normally been performed with nanostructured films that allow for control of molecular architectures. In this paper, we investigate the adsorption of uricase onto Langmuir monolayers of stearic acid (SA), and their transfer to solid supports as Langmuir-Blodgett (LB) films. Structuring of the enzyme in β-sheets was preserved in the form of 1-layer LB film, which was corroborated with a higher catalytic activity than for other uricase-containing LB film architectures where the β-sheets structuring was not preserved. The optimized architecture was also used to detect uric acid within a range covering typical concentrations in the human blood. The approach presented here not only allows for an optimized catalytic activity toward uric acid but also permits one to explain why some film architectures exhibit a superior performance. Copyright © 2011 Elsevier Inc. All rights reserved.

Atomic modeling of cryo-electron microscopy reconstructions--joint refinement of model and imaging parameters.

PubMed

Chapman, Michael S; Trzynka, Andrew; Chapman, Brynmor K

2013-04-01

When refining the fit of component atomic structures into electron microscopic reconstructions, use of a resolution-dependent atomic density function makes it possible to jointly optimize the atomic model and imaging parameters of the microscope. Atomic density is calculated by one-dimensional Fourier transform of atomic form factors convoluted with a microscope envelope correction and a low-pass filter, allowing refinement of imaging parameters such as resolution, by optimizing the agreement of calculated and experimental maps. A similar approach allows refinement of atomic displacement parameters, providing indications of molecular flexibility even at low resolution. A modest improvement in atomic coordinates is possible following optimization of these additional parameters. Methods have been implemented in a Python program that can be used in stand-alone mode for rigid-group refinement, or embedded in other optimizers for flexible refinement with stereochemical restraints. The approach is demonstrated with refinements of virus and chaperonin structures at resolutions of 9 through 4.5 Å, representing regimes where rigid-group and fully flexible parameterizations are appropriate. Through comparisons to known crystal structures, flexible fitting by RSRef is shown to be an improvement relative to other methods and to generate models with all-atom rms accuracies of 1.5-2.5 Å at resolutions of 4.5-6 Å. Copyright © 2013 Elsevier Inc. All rights reserved.

Protons, osmolytes, and fitness of internal milieu for protein function.

PubMed

Somero, G N

1986-08-01

The composition of the intracellular milieu shows striking similarities among widely different species. Only certain values of intracellular pH, values that generally reflect alphastat regulation, and only narrow ranges of inorganic ion concentrations are found in the cytoplasm of the cells of most animals, plants, and microorganisms. In water-stressed organisms only a few types of low-molecular-weight organic molecules (osmolytes) are accumulated. These highly conserved characteristics of the intracellular fluids reflect the need to maintain critical features of macromolecules within narrow ranges optimal for life. For proteins these features include maintaining adequate rates of catalysis, a high level of regulatory responsiveness, and a precise balance between stability and lability of structure (tertiary conformation, subunit assembly, and multiprotein complexes). The optimal values for these functional and structural features of proteins often lie near the midrange of possible values for these properties, and only under specific conditions of intracellular pH, ionic strength, and osmolyte composition are these optimal midrange values conserved. In dormant cells the departure of solution conditions from values that are optimal for protein function and structure may be instrumental in reducing or shutting down metabolic functions. Seen from a broad evolutionary perspective, the evolution of the intracellular milieu is an important complement to macromolecular evolution. In certain instances appropriate modifications of the internal milieu may reduce the need for adaptive amino acid replacements in proteins.

Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models

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

Esposito, Emilio Xavier, E-mail: emilio@exeResearch.com; The Chem21 Group, Inc., 1780 Wilson Drive, Lake Forest, IL 60045; Hopfinger, Anton J., E-mail: hopfingr@gmail.com

2015-10-01

Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted frommore » the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints. - Highlights: • Proposed toxicity mechanism of action for decorated nanotubes complexes • Discussion of the key molecular features for each endpoint's mechanism of action • Unique mechanisms of action for each of the six biological systems • Hypothesized mechanisms of action based on QSAR/QNAR predictive models.« less

Super-reduced polyoxometalates: excellent molecular cluster battery components and semipermeable molecular capacitors.

PubMed

Nishimoto, Yoshio; Yokogawa, Daisuke; Yoshikawa, Hirofumi; Awaga, Kunio; Irle, Stephan

2014-06-25

Theoretical investigations are presented on the molecular and electronic structure changes that occur as α-Keggin-type polyoxometalate (POM(3-)) clusters [PM12O40](3-) (M = Mo, W) are converted toward their super-reduced POM(27-) state during the discharging process in lithium-based molecular cluster batteries. Density functional theory was employed in geometry optimization, and first-principles molecular dynamics simulations were used to explore local minima on the potential energy surface of neutral POM clusters adorned with randomly placed Li atoms as electron donors around the cluster surface. On the basis of structural, electron density, and molecular orbital studies, we present evidence that the super-reduction is accompanied by metal-metal bond formation, beginning from the 12th to 14th excess electron transferred to the cluster. Afterward, the number of metal-metal bonds increases nearly linearly with the number of additionally transferred excess electrons. In α-Keggin-type POMs, metal triangles are a prominently emerging structural feature. The origin of the metal triangle formation during super-reduction stems from the formation of characteristic three-center two-electron bonds in triangular metal atom sites, created under preservation of the POM skeleton via "squeezing out" of oxygen atoms bridging two metal atoms when the underlying metal atoms form covalent bonds. The driving force for this unusual geometrical and electronic structure change is a local Jahn-Teller distortion at individual transition-metal octahedral sites, where the triply degenerate t2 d orbitals become partially filled during reduction and gain energy by distortion of the octahedron in such a way that metal-metal bonds are formed. The bonding orbitals show strong contributions from mixing with metal-oxygen antibonding orbitals, thereby "shuffling away" excess electrons from the cluster center to the outside of the cage. The high density of negatively charged yet largely separated oxygen atoms on the surface of the super-reduced POM(27-) polyanion allows the huge Coulombic repulsion due to the presence of the excess electrons to be counterbalanced by the presence of Li countercations, which partially penetrate into the outer oxygen shell. This "semiporous molecular capacitor" structure is likely the reason for the effective electron uptake in POMs.

Turbocharged molecular discovery of OLED emitters: from high-throughput quantum simulation to highly efficient TADF devices

NASA Astrophysics Data System (ADS)

Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D.; Ha, Dong-Gwang; Einzinger, Markus; Wu, Tony; Baldo, Marc A.; Aspuru-Guzik, Alán.

2016-09-01

Discovering new OLED emitters requires many experiments to synthesize candidates and test performance in devices. Large scale computer simulation can greatly speed this search process but the problem remains challenging enough that brute force application of massive computing power is not enough to successfully identify novel structures. We report a successful High Throughput Virtual Screening study that leveraged a range of methods to optimize the search process. The generation of candidate structures was constrained to contain combinatorial explosion. Simulations were tuned to the specific problem and calibrated with experimental results. Experimentalists and theorists actively collaborated such that experimental feedback was regularly utilized to update and shape the computational search. Supervised machine learning methods prioritized candidate structures prior to quantum chemistry simulation to prevent wasting compute on likely poor performers. With this combination of techniques, each multiplying the strength of the search, this effort managed to navigate an area of molecular space and identify hundreds of promising OLED candidate structures. An experimentally validated selection of this set shows emitters with external quantum efficiencies as high as 22%.

DFT calculations on spectroscopic and structural properties of a NLO chromophore

NASA Astrophysics Data System (ADS)

Altürk, Sümeyye; Avci, Davut; Tamer, Ömer; Atalay, Yusuf

2016-03-01

The molecular geometry optimization, vibrational frequencies and gauge including atomic orbital (GIAO) 1H and 13C NMR chemical shift values of 2-(1'-(4'''-Methoxyphenyl)-5'-(thien-2″-yl)pyrrol-2'-yl)-1,3-benzothiazole as potential nonlinear optical (NLO) material were calculated using density functional theory (DFT) HSEh1PBE method with 6-311G(d,p) basis set. The best of our knowledge, this study have not been reported to date. Additionally, a detailed vibrational study was performed on the basis of potential energy distribution (PED) using VEDA program. It is noteworthy that NMR chemical shifts are quite useful for understanding the relationship between the molecular structure and electronic properties of molecules. The computed IR and NMR spectra were used to determine the types of the experimental bands observed. Predicted values of structural and spectroscopic parameters of the chromophore were compared with each other so as to display the effects of the different substituents on the spectroscopic and structural properties. Obtained data showed that there is an agreement between the predicted and experimental data.

Motional timescale predictions by molecular dynamics simulations: case study using proline and hydroxyproline sidechain dynamics.

PubMed

Aliev, Abil E; Kulke, Martin; Khaneja, Harmeet S; Chudasama, Vijay; Sheppard, Tom D; Lanigan, Rachel M

2014-02-01

We propose a new approach for force field optimizations which aims at reproducing dynamics characteristics using biomolecular MD simulations, in addition to improved prediction of motionally averaged structural properties available from experiment. As the source of experimental data for dynamics fittings, we use (13) C NMR spin-lattice relaxation times T1 of backbone and sidechain carbons, which allow to determine correlation times of both overall molecular and intramolecular motions. For structural fittings, we use motionally averaged experimental values of NMR J couplings. The proline residue and its derivative 4-hydroxyproline with relatively simple cyclic structure and sidechain dynamics were chosen for the assessment of the new approach in this work. Initially, grid search and simplexed MD simulations identified large number of parameter sets which fit equally well experimental J couplings. Using the Arrhenius-type relationship between the force constant and the correlation time, the available MD data for a series of parameter sets were analyzed to predict the value of the force constant that best reproduces experimental timescale of the sidechain dynamics. Verification of the new force-field (termed as AMBER99SB-ILDNP) against NMR J couplings and correlation times showed consistent and significant improvements compared to the original force field in reproducing both structural and dynamics properties. The results suggest that matching experimental timescales of motions together with motionally averaged characteristics is the valid approach for force field parameter optimization. Such a comprehensive approach is not restricted to cyclic residues and can be extended to other amino acid residues, as well as to the backbone. Copyright © 2013 Wiley Periodicals, Inc.

Optimal estimation retrievals of the atmospheric structure and composition of HD 189733b from secondary eclipse spectroscopy

NASA Astrophysics Data System (ADS)

Lee, J.-M.; Fletcher, L. N.; Irwin, P. G. J.

2012-02-01

Recent spectroscopic observations of transiting hot Jupiters have permitted the derivation of the thermal structure and molecular abundances of H2O, CO2, CO and CH4 in these extreme atmospheres. Here, for the first time, we apply the technique of optimal estimation to determine the thermal structure and composition of an exoplanet by solving the inverse problem. The development of a suite of radiative transfer and retrieval tools for exoplanet atmospheres is described, building upon a retrieval algorithm which is extensively used in the study of our own Solar system. First, we discuss the plausibility of detection of different molecules in the dayside atmosphere of HD 189733b and the best-fitting spectrum retrieved from all publicly available sets of secondary eclipse observations between 1.45 and 24 μm. Additionally, we use contribution functions to assess the vertical sensitivity of the emission spectrum to temperatures and molecular composition. Over the altitudes probed by the contribution functions, the retrieved thermal structure shows an isothermal upper atmosphere overlying a deeper adiabatic layer (temperature decreasing with altitude), which is consistent with previously reported dynamical and observational results. The formal uncertainties on retrieved parameters are estimated conservatively using an analysis of the cross-correlation functions and the degeneracy between different atmospheric properties. The formal solution of the inverse problem suggests that the uncertainties on retrieved parameters are larger than suggested in previous studies, and that the presence of CO and CH4 is only marginally supported by the available data. Nevertheless, by including as broad a wavelength range as possible in the retrieval, we demonstrate that available spectra of HD 189733b can constrain a family of potential solutions for the atmospheric structure.

Structural, vibrational spectroscopic and nonlinear optical activity studies on 2-hydroxy- 3, 5-dinitropyridine: A DFT approach

NASA Astrophysics Data System (ADS)

Asath, R. Mohamed; Premkumar, S.; Jawahar, A.; Mathavan, T.; Dhas, M. Kumara; Benial, A. Milton Franklin

2015-06-01

The conformational analysis was carried out for 2-Hydroxy- 3, 5-dinitropyridine molecule using potential energy surface scan and the most stable optimized conformer was predicted. The vibrational frequencies and Mulliken atomic charge distribution were calculated for the optimized geometry of the molecule using DFT/B3LYP cc-pVQZ basis set by Gaussian 09 Program. The vibrational frequencies were assigned on the basis of potential energy distribution calculation using VEDA 4.0 program. In the Frontier molecular orbitals analysis, the molecular reactivity, kinetic stability, intramolecular charge transfer studies and the calculation of ionization energy, electron affinity, global hardness, chemical potential, electrophilicity index and softness values of the title molecule were carried out. The nonlinear optical activity of the molecule was studied by means of first order hyperpolarizability, which was computed as 7.64 times greater than urea. The natural bond orbital analysis was performed to confirm the nonlinear optical activity of the molecule.

Separation of three phenolic high-molecular-weight compounds from the crude extract of Terminalia Chebula Retz. by ultrasound-assisted extraction and high-speed counter-current chromatography.

PubMed

Zou, Deng-lang; Chen, Tao; Li, Hong-mei; Chen, Chen; Zhao, Jing-yang; Li, Yu-lin

2016-04-01

This study presents an efficient strategy for separation of three phenolic compounds with high molecular weight from the crude extract of Terminalia chebula Retz. by ultrasound-assisted extraction and high-speed counter-current chromatography. The ultrasound-assisted extraction conditions were optimized by response surface methodology and the results showed the target compounds could be well enriched under the optimized extraction conditions. Then the crude extract was directly separated by high-speed counter-current chromatography without any pretreatment using n-hexane/ethyl acetate/methanol/water (1:7:0.5:3, v/v/v/v) as the solvent system. In 180 min, 13 mg of A, 18 mg of B, and 9 mg of C were obtained from 200 mg of crude sample. Their structures were identified as Chebulagic acid (A, 954 Da), Chebulinic acid (B, 956 Da), and Ellagic acid (C) by (1) H NMR spectroscopy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biolayer modeling and optimization for the SPARROW biosensor

NASA Astrophysics Data System (ADS)

Feng, Ke

2007-12-01

Biosensor direct detection of molecular binding events is of significant interest in applications from molecular screening for cancer drug design to bioagent detection for homeland security and defense. The Stacked Planar Affinity Regulated Resonant Optical Waveguide (SPARROW) structure based on coupled waveguides was recently developed to achieve increased sensitivity within a fieldable biosensor device configuration. Under ideal operating conditions, modification of the effective propagation constant of the structure's sensing waveguide through selective attachment of specific targets to probes on the waveguide surface results in a change in the coupling characteristics of the guide over a specifically designed interaction length with the analyte. Monitoring the relative power in each waveguide after interaction enables 'recognition' of those targets which have selectively bound to the surface. However, fabrication tolerances, waveguide interface roughness, biolayer surface roughness and biolayer partial coverage have an effect on biosensor behavior and achievable limit of detection (LOD). In addition to these influences which play a role in device optimization, the influence of the spatially random surface loading of molecular binding events has to be considered, especially for low surface coverage. In this dissertation an analytic model is established for the SPARROW biosensor which accounts for these nonidealities with which the design of the biosensor can be guided and optimized. For the idealized case of uniform waveguide transducer layers and biolayer, both theoretical simulation (analytical expression) and computer simulation (numerical calculation) are completed. For the nonideal case of an inhomogeneous transducer with nonideal waveguide and biolayer surfaces, device output power is affected by such physical influences as surface scattering, coupling length, absorption, and percent coverage of binding events. Using grating and perturbation techniques we explore the influence of imperfect surfaces and random surface loading on scattering loss and coupling length. Results provide a range of achievable limits of detection in the SPARROW device for a given target size, surface loading, and detectable optical power.

Adiabatic quantum computing with spin qubits hosted by molecules.

PubMed

Yamamoto, Satoru; Nakazawa, Shigeaki; Sugisaki, Kenji; Sato, Kazunobu; Toyota, Kazuo; Shiomi, Daisuke; Takui, Takeji

2015-01-28

A molecular spin quantum computer (MSQC) requires electron spin qubits, which pulse-based electron spin/magnetic resonance (ESR/MR) techniques can afford to manipulate for implementing quantum gate operations in open shell molecular entities. Importantly, nuclear spins, which are topologically connected, particularly in organic molecular spin systems, are client qubits, while electron spins play a role of bus qubits. Here, we introduce the implementation for an adiabatic quantum algorithm, suggesting the possible utilization of molecular spins with optimized spin structures for MSQCs. We exemplify the utilization of an adiabatic factorization problem of 21, compared with the corresponding nuclear magnetic resonance (NMR) case. Two molecular spins are selected: one is a molecular spin composed of three exchange-coupled electrons as electron-only qubits and the other an electron-bus qubit with two client nuclear spin qubits. Their electronic spin structures are well characterized in terms of the quantum mechanical behaviour in the spin Hamiltonian. The implementation of adiabatic quantum computing/computation (AQC) has, for the first time, been achieved by establishing ESR/MR pulse sequences for effective spin Hamiltonians in a fully controlled manner of spin manipulation. The conquered pulse sequences have been compared with the NMR experiments and shown much faster CPU times corresponding to the interaction strength between the spins. Significant differences are shown in rotational operations and pulse intervals for ESR/MR operations. As a result, we suggest the advantages and possible utilization of the time-evolution based AQC approach for molecular spin quantum computers and molecular spin quantum simulators underlain by sophisticated ESR/MR pulsed spin technology.

Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors.

PubMed

Kwiatkowski, Jacek; Liu, Boping; Tee, Doris Hui Ying; Chen, Guoying; Ahmad, Nur Huda Binte; Wong, Yun Xuan; Poh, Zhi Ying; Ang, Shi Hua; Tan, Eldwin Sum Wai; Ong, Esther Hq; Nurul Dinie; Poulsen, Anders; Pendharkar, Vishal; Sangthongpitag, Kanda; Lee, May Ann; Sepramaniam, Sugunavathi; Ho, Soo Yei; Cherian, Joseph; Hill, Jeffrey; Keller, Thomas H; Hung, Alvin W

2018-05-24

Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.

Design of Supercapacitor Electrodes Using Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Bo, Zheng; Li, Changwen; Yang, Huachao; Ostrikov, Kostya; Yan, Jianhua; Cen, Kefa

2018-06-01

Electric double-layer capacitors (EDLCs) are advanced electrochemical devices for energy storage and have attracted strong interest due to their outstanding properties. Rational optimization of electrode-electrolyte interactions is of vital importance to enhance device performance for practical applications. Molecular dynamics (MD) simulations could provide theoretical guidelines for the optimal design of electrodes and the improvement of capacitive performances, e.g., energy density and power density. Here we discuss recent MD simulation studies on energy storage performance of electrode materials containing porous to nanostructures. The energy storage properties are related to the electrode structures, including electrode geometry and electrode modifications. Altering electrode geometry, i.e., pore size and surface topography, can influence EDL capacitance. We critically examine different types of electrode modifications, such as altering the arrangement of carbon atoms, doping heteroatoms and defects, which can change the quantum capacitance. The enhancement of power density can be achieved by the intensified ion dynamics and shortened ion pathway. Rational control of the electrode morphology helps improve the ion dynamics by decreasing the ion diffusion pathway. Tuning the surface properties (e.g., the affinity between the electrode and the ions) can affect the ion-packing phenomena. Our critical analysis helps enhance the energy and power densities of EDLCs by modulating the corresponding electrode structures and surface properties.[Figure not available: see fulltext.

A capillary electrophoretic method for fingerprinting low molecular weight heparins.

PubMed

King, J Timothy; Desai, Umesh R

2008-09-15

Clinically used low molecular weight heparins (LMWH) are anticoagulants of choice and are phenomenally complex mixtures of millions of distinct natural and unnatural polymeric sequences. The FDA recommends that each LMWH be considered as an independent drug with its own activity profile, placing significant importance on the biophysical characterization of each intact LMWH. We report a robust protocol for fingerprinting these pharmaceutical agents. Capillary electrophoresis of three LMWHs, enoxaparin, tinzaparin, and a Sigma preparation, under reverse polarity conditions in the presence of selected linear alkyl polyamines gives an electrophoretic pattern that is characteristic of the nature of the starting material. The buffers that best provided optimal resolution without compromising sensitivity and speed of analysis were 50 mM sodium phosphate, pH 2.3, and 100 mM ammonium formate, pH 3.5. Resolution was strongly dependent on the structure of polyamine with pentaethylenehexamine being most effective for enoxaparin and Sigma LMWH. In contrast, tinzaparin could be best resolved with tetraethylenepentamine. Cyclic polyamines were ineffective. Resolution was also dependent on the concentration of resolving agents and displayed a narrow window that provides optimal resolution. These features suggest a strong structural origin of the fingerprint pattern. Overall, the simple protocol will find special use in assessing LMWH quality and batch-to-batch variability.

Determination of solute descriptors by chromatographic methods.

PubMed

Poole, Colin F; Atapattu, Sanka N; Poole, Salwa K; Bell, Andrea K

2009-10-12

The solvation parameter model is now well established as a useful tool for obtaining quantitative structure-property relationships for chemical, biomedical and environmental processes. The model correlates a free-energy related property of a system to six free-energy derived descriptors describing molecular properties. These molecular descriptors are defined as L (gas-liquid partition coefficient on hexadecane at 298K), V (McGowan's characteristic volume), E (excess molar refraction), S (dipolarity/polarizability), A (hydrogen-bond acidity), and B (hydrogen-bond basicity). McGowan's characteristic volume is trivially calculated from structure and the excess molar refraction can be calculated for liquids from their refractive index and easily estimated for solids. The remaining four descriptors are derived by experiment using (largely) two-phase partitioning, chromatography, and solubility measurements. In this article, the use of gas chromatography, reversed-phase liquid chromatography, micellar electrokinetic chromatography, and two-phase partitioning for determining solute descriptors is described. A large database of experimental retention factors and partition coefficients is constructed after first applying selection tools to remove unreliable experimental values and an optimized collection of varied compounds with descriptor values suitable for calibrating chromatographic systems is presented. These optimized descriptors are demonstrated to be robust and more suitable than other groups of descriptors characterizing the separation properties of chromatographic systems.

Transitioning NWChem to the Next Generation of Manycore Machines

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

Bylaska, Eric J.; Apra, E; Kowalski, Karol

The NorthWest chemistry (NWChem) modeling software is a popular molecular chemistry simulation software that was designed from the start to work on massively parallel processing supercomputers [1-3]. It contains an umbrella of modules that today includes self-consistent eld (SCF), second order Møller-Plesset perturbation theory (MP2), coupled cluster (CC), multiconguration self-consistent eld (MCSCF), selected conguration interaction (CI), tensor contraction engine (TCE) many body methods, density functional theory (DFT), time-dependent density functional theory (TDDFT), real-time time-dependent density functional theory, pseudopotential plane-wave density functional theory (PSPW), band structure (BAND), ab initio molecular dynamics (AIMD), Car-Parrinello molecular dynamics (MD), classical MD, hybrid quantum mechanicsmore » molecular mechanics (QM/MM), hybrid ab initio molecular dynamics molecular mechanics (AIMD/MM), gauge independent atomic orbital nuclear magnetic resonance (GIAO NMR), conductor like screening solvation model (COSMO), conductor-like screening solvation model based on density (COSMO-SMD), and reference interaction site model (RISM) solvation models, free energy simulations, reaction path optimization, parallel in time, among other capabilities [4]. Moreover, new capabilities continue to be added with each new release.« less

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations.

PubMed

Gao, Xiaodong; Han, Liping; Ren, Yujie

2016-05-05

Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q² values (0.531, 0.726), fitted correlation r² coefficients (higher than 0.90), and standard error of prediction (less than 0.250). These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity.

Structural Refinement of Membrane Proteins by Restrained Molecular Dynamics and Solvent Accessibility Data

PubMed Central

Sompornpisut, Pornthep; Roux, Benoît; Perozo, Eduardo

2008-01-01

We present an approach for incorporating solvent accessibility data from electron paramagnetic resonance experiments in the structural refinement of membrane proteins through restrained molecular dynamics simulations. The restraints have been parameterized from oxygen (ΠO2) and nickel-ethylenediaminediacetic acid (ΠNiEdda) collision frequencies, as indicators of lipid or aqueous exposed spin-label sites. These are enforced through interactions between a pseudoatom representation of the covalently attached Nitroxide spin-label and virtual “solvent” particles corresponding to O2 and NiEdda in the surrounding environment. Interactions were computed using an empirical potential function, where the parameters have been optimized to account for the different accessibilities of the spin-label pseudoatoms to the surrounding environment. This approach, “pseudoatom-driven solvent accessibility refinement”, was validated by refolding distorted conformations of the Streptomyces lividans potassium channel (KcsA), corresponding to a range of 2–30 Å root mean-square deviations away from the native structure. Molecular dynamics simulations based on up to 58 electron paramagnetic resonance restraints derived from spin-label mutants were able to converge toward the native structure within 1–3 Å root mean-square deviations with minimal computational cost. The use of energy-based ranking and structure similarity clustering as selection criteria helped in the convergence and identification of correctly folded structures from a large number of simulations. This approach can be applied to a variety of integral membrane protein systems, regardless of oligomeric state, and should be particularly useful in calculating conformational changes from a known reference crystal structure. PMID:18676641

Turning Defense into Offense: Defensin Mimetics as Novel Antibiotics Targeting Lipid II

PubMed Central

Ateh, Eugene; Oashi, Taiji; Lu, Wuyuan; Huang, Jing; Diepeveen-de Buin, Marlies; Bryant, Joseph; Breukink, Eefjan; MacKerell, Alexander D.; de Leeuw, Erik P. H.

2013-01-01

We have previously reported on the functional interaction of Lipid II with human alpha-defensins, a class of antimicrobial peptides. Lipid II is an essential precursor for bacterial cell wall biosynthesis and an ideal and validated target for natural antibiotic compounds. Using a combination of structural, functional and in silico analyses, we present here the molecular basis for defensin-Lipid II binding. Based on the complex of Lipid II with Human Neutrophil peptide-1, we could identify and characterize chemically diverse low-molecular weight compounds that mimic the interactions between HNP-1 and Lipid II. Lead compound BAS00127538 was further characterized structurally and functionally; it specifically interacts with the N-acetyl muramic acid moiety and isoprenyl tail of Lipid II, targets cell wall synthesis and was protective in an in vivo model for sepsis. For the first time, we have identified and characterized low molecular weight synthetic compounds that target Lipid II with high specificity and affinity. Optimization of these compounds may allow for their development as novel, next generation therapeutic agents for the treatment of Gram-positive pathogenic infections. PMID:24244161

Sharp organic interface of molecular C60 chains and a pentacene derivative SAM on Au(788): A combined STM & DFT study

NASA Astrophysics Data System (ADS)

Wang, Jun; Tang, Jian-Ming; Larson, Amanda M.; Miller, Glen P.; Pohl, Karsten

2013-12-01

Controlling the molecular structure of the donor-acceptor interface is essential to overcoming the efficiency bottleneck in organic photovoltaics. We present a study of self-assembled fullerene (C60) molecular chains on perfectly ordered 6,13-dichloropentacene (DCP) monolayers forming on a vicinal Au(788) surface using scanning tunneling microscopy in conjunction with density functional theory calculations. DCP is a novel pentacene derivative optimized for photovoltaic applications. The molecules form a brick-wall patterned centered rectangular lattice with the long axis parallel to the monatomic steps that separate the 3.9 nm wide Au(111) terraces. The strong interaction between the C60 molecules and the gold substrate is well screened by the DCP monolayer. At submonolayer C60 coverage, the fullerene molecules form long parallel chains, 1.1 nm apart, with a rectangular arrangement instead of the expected close-packed configuration along the upper step edges. The perfectly ordered DCP structure is unaffected by the C60 chain formation. The controlled sharp highly-ordered organic interface has the potential to improve the conversion efficiency in organic photovoltaics.

Experimental and quantum chemical studies of a new organic proton transfer compound, 1H-imidazole-3-ium-3-hydroxy-2,4,6-trinitrophenolate

NASA Astrophysics Data System (ADS)

Dhamodharan, P.; Sathya, K.; Dhandapani, M.

2018-02-01

A new proton transfer compound, 1H-imidazole-3-ium-3-hydroxy-2,4,6-trinitrophenolate (IMHTP), was crystallized by slow evaporation-solution growth technique. 1H and 13C NMR spectral studies confirm the molecular structure of the grown crystal. Single crystal X-ray diffraction study confirms that IMHTP crystallizes in monoclinic system with space group P21/c. Thermal curves (TG/DTA) show that the material is thermally stable up to 198 °C. The crystal emits fluorescence at 510 nm, proving its utility in making green light emitting materials in optical applications. The stable molecular structure was optimized by Gaussian 09 program with B3LYP/6-311++G(d,p) level of basis set. The frontier molecular orbital study shows that the charge transfer interaction occurs within the complex. The calculated first-order hyperpolarizability value of IMHTP is 44 times higher than that the reference material, urea. The electrostatic potential map was used to probe into electrophilic and nucleophilic reactive sites present in the molecule.

Investigation of the graphene-electrolyte interface in Li-air batteries: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Pavlov, S. V.; Kislenko, S. A.

2018-01-01

In this work the behavior of the main reactants (Li+, O2) of the oxygen reduction reaction (ORR) in acetonitrile solvent near the multi-layer graphene edge has been studied. It was observed by molecular dynamics simulations that the concentration distributions of the Li+ and O2 represent a “chessboard” structure. It was ascertained that the concentrations of the lithium ions and oxygen molecules reach their maximum values near the graphene edges pushed out from the surface, which may act as nucleation centers for the formation of crystalline products of the ORR. The maps of the free energy were estimated for the Li+ and O2. Energy optimal trajectories for the adsorption of oxygen molecules and lithium ions were found. Moreover, the distributions of the electric potential were obtained near the following carbon surfaces: single- and multi-layer graphene edge, graphene plane, which shows the qualitative differences in the double-layer structure.

Scaffold-based novel SHP2 allosteric inhibitors design using Receptor-Ligand pharmacophore model, virtual screening and molecular dynamics.

PubMed

Jin, Wen-Yan; Ma, Ying; Li, Wei-Ya; Li, Hong-Lian; Wang, Run-Ling

2018-04-01

SHP2 is a potential target for the development of novel therapies for SHP2-dependent cancers. In our research, with the aid of the 'Receptor-Ligand Pharmacophore' technique, a 3D-QSAR method was carried out to explore structure activity relationship of SHP2 allosteric inhibitors. Structure-based drug design was employed to optimize SHP099, an efficacious, potent, and selective SHP2 allosteric inhibitor. A novel class of selective SHP2 allosteric inhibitors was discovered by using the powerful 'SBP', 'ADMET' and 'CDOCKER' techniques. By means of molecular dynamics simulations, it was observed that these novel inhibitors not only had the same function as SHP099 did in inhibiting SHP2, but also had more favorable conformation for binding to the receptor. Thus, this report may provide a new method in discovering novel and selective SHP2 allosteric inhibitors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular Containers Bind Drugs of Abuse in Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in Rats.

PubMed

Ganapati, Shweta; Grabitz, Stephanie D; Murkli, Steven; Scheffenbichler, Flora; Rudolph, Maíra I; Zavalij, Peter Y; Eikermann, Matthias; Isaacs, Lyle

2017-08-17

We measured the affinity of five molecular container compounds (calabadions 1 and 2, CB[7], sulfocalix[4]arene, and HP-β-CD) toward seven drugs of abuse in homogenous aqueous solution at physiological pH by various methods ( 1 H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants (K a values) spanning from <10 2 to >10 8  m -1 . We also report X-ray crystal structures of CB[7]⋅methamphetamine and 1⋅methamphetamine. We found that 2, but not CB[7], was able to ameliorate the hyperlocomotive activity of rats treated with methamphetamine. The bioavailability of the calabadions and their convergent building block synthesis suggest potential for further structural optimization as reversal agents for intoxication with nonopioid drugs of abuse for which no treatments are currently available. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrolyte Structure near Electrode Interfaces in Lithium-Ion Batteries

NASA Astrophysics Data System (ADS)

Lordi, Vincenzo; Ong, Mitchell; Verners, Osvalds; van Duin, Adri; Draeger, Erik; Pask, John

2014-03-01

The performance of lithium-ion secondary batteries (LIBs) is strongly tied to electrochemistry and ionic transport near the electrode-electrolyte interface. Changes in ion solvation near the interface affect ion conductivity and also are associated with the formation and evolution of solid-electrolyte interphase (SEI) layers, which impede transport but also passivate the interface. Thus, understanding these effects is critical to optimizing battery performance. Here we present molecular dynamics (MD) simulations of typical organic liquid LIB electrolytes in contact with graphite electrodes to understand differences in molecular structure and solvation near the interface compared to the bulk electrolyte. Results for different graphite terminations are presented. We compare the results of density-functional based MD to the empirical reactive forcefield ReaxFF and the non-reactive, non-polarizable COMPASS forcefield. Notable differences in the predictive power of each of these techniques are discussed. Prepared by LLNL under Contract DE-AC52-07NA27344.

Covalent modification of graphene and graphite using diazonium chemistry: tunable grafting and nanomanipulation.

PubMed

Greenwood, John; Phan, Thanh Hai; Fujita, Yasuhiko; Li, Zhi; Ivasenko, Oleksandr; Vanderlinden, Willem; Van Gorp, Hans; Frederickx, Wout; Lu, Gang; Tahara, Kazukuni; Tobe, Yoshito; Uji-I, Hiroshi; Mertens, Stijn F L; De Feyter, Steven

2015-05-26

We shine light on the covalent modification of graphite and graphene substrates using diazonium chemistry under ambient conditions. We report on the nature of the chemical modification of these graphitic substrates, the relation between molecular structure and film morphology, and the impact of the covalent modification on the properties of the substrates, as revealed by local microscopy and spectroscopy techniques and electrochemistry. By careful selection of the reagents and optimizing reaction conditions, a high density of covalently grafted molecules is obtained, a result that is demonstrated in an unprecedented way by scanning tunneling microscopy (STM) under ambient conditions. With nanomanipulation, i.e., nanoshaving using STM, surface structuring and functionalization at the nanoscale is achieved. This manipulation leads to the removal of the covalently anchored molecules, regenerating pristine sp(2) hybridized graphene or graphite patches, as proven by space-resolved Raman microscopy and molecular self-assembly studies.

Studies on molecular structure and tautomerism of a vitamin B6 analog with density functional theory.

PubMed

Sahoo, Suban K; Sharma, Darshna; Bera, Rati Kanta

2012-05-01

This work presents a computational study on the molecular structure and tautomeric equilibria of a novel Schiff base L derived from pyridoxal (PL) and o-phenylenediamine by using the density functional method B3LYP with basis sets 6-31 G(d,p), 6-31++G(d,p), 6-311 G(d,p) and 6-311++G(d,p). The optimized geometrical parameters obtained by B3LYP/6-31 G(d,p) method showed the best agreement with the experimental values. Tautomeric stability study of L inferred that the enolimine form is more stable than its ketoenamine form in both gas phase and solution. However, protonation of the pyridoxal nitrogen atom (LH) have accelerated the formation of ketoenamine form, and therefore, both ketoenamine and enolimine forms could be present in acidic media.

Synthesis, crystal structure, biological activity and theoretical calculations of novel isoxazole derivatives

NASA Astrophysics Data System (ADS)

Jin, R. Y.; Sun, X. H.; Liu, Y. F.; Long, W.; Chen, B.; Shen, S. Q.; Ma, H. X.

2016-01-01

Series of isoxazole derivatives were synthesized by substituted chalcones and 2-chloro-6-fluorobenzene formaldehyde oxime with 1,3-dipolar cycloaddition. The target compounds were determined by melting point, IR, 1H NMR, elemental analyses and HRMS. The crystal structure of compound 3a was detected by X-ray diffraction and it crystallizes in the triclinic space group p2(1)/c with z = 4. The molecular geometry of compound 3a was optimized using density functional theory (DFT/B3LYP) method with the 6-31G+(d,p) basis set in the ground state. From the optimized geometry of the molecule, FT-IR, FT-Raman, HOMO-LUMO and natural bond orbital (NBO) were calculated at B3LYP/6-31G+(d,p) level. Finally, the antifungal activity of the synthetic compounds were evaluated against Pythium solani, Gibberella nicotiancola, Fusarium oxysporium f.sp. niveum and Gibberella saubinetii.

Unified interatomic potential and energy barrier distributions for amorphous oxides.

PubMed

Trinastic, J P; Hamdan, R; Wu, Y; Zhang, L; Cheng, Hai-Ping

2013-10-21

Amorphous tantala, titania, and hafnia are important oxides for biomedical implants, optics, and gate insulators. Understanding the effects of oxide doping is crucial to optimize performance in these applications. However, no molecular dynamics potentials have been created to date that combine these and other oxides that would allow computational analyses of doping-dependent structural and mechanical properties. We report a novel set of computationally efficient, two-body potentials modeling van der Waals and covalent interactions that reproduce the structural and elastic properties of both pure and doped amorphous oxides. In addition, we demonstrate that the potential accurately produces energy barrier distributions for pure and doped samples. The distributions can be directly compared to experiment and used to calculate physical quantities such as internal friction to understand how doping affects material properties. Future analyses using these potentials will be of great value to determine optimal doping concentrations and material combinations for myriad material science applications.

Nuclear magnetic resonance spectral analysis and molecular properties of berberine

NASA Astrophysics Data System (ADS)

Huang, Ming-Ju; Lee, Ken S.; Hurley, Sharon J.

An extensive theoretical study of berberine has been performed at the ab initio HF/6-31G**, HF/6-311G**, and B3LYP/6-311G** levels with and without solvent effects. The optimized structures are compared with X-ray data. We found that the optimized structures with solvent effects are in slightly better agreement with X-ray data than those without solvent effects. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of berberine were calculated by using the gauge-independent atomic orbital (GIAO) (with and without solvent effects), CSGT, and IGAIM methods. The calculated chemical shifts were compared with the two-dimensional NMR experimental data. Overall, the calculated chemical shifts show very good agreement with the experimental results. The harmonic vibrational frequencies for berberine were calculated at the B3LYP/6-311G** level.

Evolution of a designed retro-aldolase leads to complete active site remodeling

PubMed Central

Giger, Lars; Caner, Sami; Obexer, Richard; Kast, Peter; Baker, David; Ban, Nenad; Hilvert, Donald

2013-01-01

Evolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that dramatic molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400 fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate, and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. PMID:23748672

Importance of many-body dispersion and temperature effects on gas-phase gold cluster (meta)stability

NASA Astrophysics Data System (ADS)

Goldsmith, Bryan R.; Gruene, Philipp; Lyon, Jonathan T.; Rayner, David M.; Fielicke, André; Scheffler, Matthias; Ghiringhelli, Luca M.

Gold clusters in the gas phase exhibit many structural isomers that are shown to intercovert frequently, even at room temperature. We performed ab initio replica-exchange molecular dynamics (REMD) calculations on gold clusters (of sizes 5-14 atoms) to identify metastable states and their relative populations at finite temperature, as well as to examine the importance of temperature and van der Waals (vdW) on their isomer energetic ordering. Free energies of the gold cluster isomers are optimally estimated using the Multistate Bennett Acceptance Ratio. The distribution of bond coordination numbers and radius of gyration are used to address the challenge of discriminating isomers along their dynamical trajectories. Dispersion effects are important for stabilizing three-dimensional structures relative to planar structures and brings isomer energetic predictions to closer quantitative agreement compared with RPA@PBE calculations. We find that higher temperatures typically stabilize metastable three-dimensional structures relative to planar/quasiplanar structures. Computed IR spectra of low free energy Au9, Au10, and Au12 isomers are in agreement with experimental spectra obtained by far-IR multiple photon dissociation in a molecular beam at 100 K.

Three oxime ether derivatives: Synthesis, crystallographic study, electronic structure and molecular electrostatic potential calculation

NASA Astrophysics Data System (ADS)

Dey, Tanusri; Praveena, Koduru Sri Shanthi; Pal, Sarbani; Mukherjee, Alok Kumar

2017-06-01

Three oxime ether derivatives, (E)-3-methoxy-4-(prop-2-ynyloxy)-benzaldehyde-O-prop-2-ynyl-oxime (C14H13NO3) (2), benzophenone-O-prop-2-ynyl-oxime (C16H13NO) (3) and (E)-2-chloro-6-methylquinoline-3-carbaldehyde-O-prop-2-ynyl-oxime (C14H11ClN2O) (4), have been synthesized and their crystal structures have been determined. The DFT optimized molecular geometries in 2-4 agree closely with those obtained from the crystallographic study. An interplay of intermolecular Csbnd H⋯O, Csbnd H⋯N, Csbnd H⋯Cl and Csbnd H···π(arene) hydrogen bonds and π···π interactions assembles molecules into a 2D columnar architecture in 2, a 1D molecular ribbon in 3 and a 3D framework in 4. Hirshfeld surface analysis showed that the structures of 2 and 3 are mainly characterized by H⋯H, H⋯C and H⋯O contacts but some contribution of H⋯N and H⋯Cl contacts is also observed in 4. Hydrogen-bond based interactions in 2-4 have been complemented by calculating molecular electrostatic potential (MEP) surfaces. The electronic structures of molecules reveal that the estimated band gap in 3, in which both aldehyde hydrogen atoms of formaldehyde-O-prop-2-ynyl-oxime (1) have been substituted by two benzene rings, is higher than that of 2 and 4 with only one aldehyde hydrogen atom replaced.

Modification and optimization of the united-residue (UNRES) potential-energy function for canonical simulations. I. Temperature dependence of the effective energy function and tests of the optimization method with single training proteins

PubMed Central

Liwo, Adam; Khalili, Mey; Czaplewski, Cezary; Kalinowski, Sebastian; Ołdziej, Stanisław; Wachucik, Katarzyna; Scheraga, Harold A.

2011-01-01

We report the modification and parameterization of the united-residue (UNRES) force field for energy-based protein-structure prediction and protein-folding simulations. We tested the approach on three training proteins separately: 1E0L (β), 1GAB (α), and 1E0G (α + β). Heretofore, the UNRES force field had been designed and parameterized to locate native-like structures of proteins as global minima of their effective potential-energy surfaces, which largely neglected the conformational entropy because decoys composed of only lowest-energy conformations were used to optimize the force field. Recently, we developed a mesoscopic dynamics procedure for UNRES, and applied it with success to simulate protein folding pathways. How ever, the force field turned out to be largely biased towards α-helical structures in canonical simulations because the conformational entropy had been neglected in the parameterization. We applied the hierarchical optimization method developed in our earlier work to optimize the force field, in which the conformational space of a training protein is divided into levels each corresponding to a certain degree of native-likeness. The levels are ordered according to increasing native-likeness; level 0 corresponds to structures with no native-like elements and the highest level corresponds to the fully native-like structures. The aim of optimization is to achieve the order of the free energies of levels, decreasing as their native-likeness increases. The procedure is iterative, and decoys of the training protein(s) generated with the energy-function parameters of the preceding iteration are used to optimize the force field in a current iteration. We applied the multiplexing replica exchange molecular dynamics (MREMD) method, recently implemented in UNRES, to generate decoys; with this modification, conformational entropy is taken into account. Moreover, we optimized the free-energy gaps between levels at temperatures corresponding to a predominance of folded or unfolded structures, as well as to structures at the putative folding-transition temperature, changing the sign of the gaps at the transition temperature. This enabled us to obtain force fields characterized by a single peak in the heat capacity at the transition temperature. Furthermore, we introduced temperature dependence to the UNRES force field; this is consistent with the fact that it is a free-energy and not a potential-energy function. PMID:17201450

Synthesis, molecular structure, Hirshfeld surface, spectral investigations and molecular docking study of 3-(5-bromo-2-thienyl)-1-(4-fluorophenyl)-3-acetyl-2-pyrazoline (2) by DFT method

NASA Astrophysics Data System (ADS)

Sathish, M.; Meenakshi, G.; Xavier, S.; Sebastian, S.; Periandy, S.; Ahmad, NoorAisyah; Jamalis, Joazaizulfazli; Rosli, MohdMustaqim; Fun, Hoong-Kun

2018-07-01

The 3-(5-Bromo-2-thienyl)-1-(4-fluorophenyl)-3-acetyl-2-pyrazoline (2) (BTFA) was synthesized from condensation of thiophenechalcone (1) and hydrazine hydrate. The compound was characterized by FT-IR, 1H and 13C NMR. Crystal structure of this compound was determined using X-ray diffraction technique. The data of the geometry is compared with the optimized structure of the compound obtained using B3LYP functional with 6-311++G (d,p) basis set. The fundamental modes of vibrations are assigned using VEDA software with the PED assignments, and compared with data obtained from theoretical methods. The deviations are widely discussed and analyzed. The intermolecular interaction of the crystal structure was analyzed using Hirshfeld and fingerprint analysis. The chemical shift of the NMR for 13C and 1H are observed and computational data are computed using Gauge independent atomic orbital (GIAO) using B3LYP/6-311++G (d,p). The electronic and optical properties like absorption of wavelengths, excitation energy, dipole moment and frontier molecular orbital energies are computed with TD-SCF method using the above theoretical method. The antiviral nature of the molecule is also analyzed and the compound is docked in non-small cell lung cancer and human collapsin response mediator protein-1study exhibits its activity.

Steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins.

PubMed

Huang, Wenxi; Liu, Wanting; Jin, Jingjie; Xiao, Qilan; Lu, Ruibin; Chen, Wei; Xiong, Sheng; Zhang, Gong

2018-03-25

Translational pausing coordinates protein synthesis and co-translational folding. It is a common factor that facilitates the correct folding of large, multi-domain proteins. For small proteins, pausing sites rarely occurs in the gene body, and the 3'-end pausing sites are only essential for the folding of a fraction of proteins. The determinant of the necessity of the pausings remains obscure. In this study, we demonstrated that the steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins. Validated by experiments with 5 model proteins, we found that the rigid protein structures do not, while the flexible structures do need 3'-end pausings to fold correctly. Therefore, rational optimization of translational pausing can improve soluble expression of small proteins with flexible structures, but not the rigid ones. The rigidity of the structure can be quantitatively estimated in silico using molecular dynamic simulation. Nevertheless, we also found that the translational pausing optimization increases the fitness of the expression host, and thus benefits the recombinant protein production, independent from the soluble expression. These results shed light on the structural basis of the translational pausing and provided a practical tool for industrial protein fermentation. Copyright © 2017. Published by Elsevier Inc.

QM/MM Geometry Optimization on Extensive Free-Energy Surfaces for Examination of Enzymatic Reactions and Design of Novel Functional Properties of Proteins.

PubMed

Hayashi, Shigehiko; Uchida, Yoshihiro; Hasegawa, Taisuke; Higashi, Masahiro; Kosugi, Takahiro; Kamiya, Motoshi

2017-05-05

Many remarkable molecular functions of proteins use their characteristic global and slow conformational dynamics through coupling of local chemical states in reaction centers with global conformational changes of proteins. To theoretically examine the functional processes of proteins in atomic detail, a methodology of quantum mechanical/molecular mechanical (QM/MM) free-energy geometry optimization is introduced. In the methodology, a geometry optimization of a local reaction center is performed with a quantum mechanical calculation on a free-energy surface constructed with conformational samples of the surrounding protein environment obtained by a molecular dynamics simulation with a molecular mechanics force field. Geometry optimizations on extensive free-energy surfaces by a QM/MM reweighting free-energy self-consistent field method designed to be variationally consistent and computationally efficient have enabled examinations of the multiscale molecular coupling of local chemical states with global protein conformational changes in functional processes and analysis and design of protein mutants with novel functional properties.

QM/MM Geometry Optimization on Extensive Free-Energy Surfaces for Examination of Enzymatic Reactions and Design of Novel Functional Properties of Proteins

NASA Astrophysics Data System (ADS)

Hayashi, Shigehiko; Uchida, Yoshihiro; Hasegawa, Taisuke; Higashi, Masahiro; Kosugi, Takahiro; Kamiya, Motoshi

2017-05-01

Many remarkable molecular functions of proteins use their characteristic global and slow conformational dynamics through coupling of local chemical states in reaction centers with global conformational changes of proteins. To theoretically examine the functional processes of proteins in atomic detail, a methodology of quantum mechanical/molecular mechanical (QM/MM) free-energy geometry optimization is introduced. In the methodology, a geometry optimization of a local reaction center is performed with a quantum mechanical calculation on a free-energy surface constructed with conformational samples of the surrounding protein environment obtained by a molecular dynamics simulation with a molecular mechanics force field. Geometry optimizations on extensive free-energy surfaces by a QM/MM reweighting free-energy self-consistent field method designed to be variationally consistent and computationally efficient have enabled examinations of the multiscale molecular coupling of local chemical states with global protein conformational changes in functional processes and analysis and design of protein mutants with novel functional properties.

Performance optimization of Qbox and WEST on Intel Knights Landing

NASA Astrophysics Data System (ADS)

Zheng, Huihuo; Knight, Christopher; Galli, Giulia; Govoni, Marco; Gygi, Francois

We present the optimization of electronic structure codes Qbox and WEST targeting the Intel®Xeon Phi™processor, codenamed Knights Landing (KNL). Qbox is an ab-initio molecular dynamics code based on plane wave density functional theory (DFT) and WEST is a post-DFT code for excited state calculations within many-body perturbation theory. Both Qbox and WEST employ highly scalable algorithms which enable accurate large-scale electronic structure calculations on leadership class supercomputer platforms beyond 100,000 cores, such as Mira and Theta at the Argonne Leadership Computing Facility. In this work, features of the KNL architecture (e.g. hierarchical memory) are explored to achieve higher performance in key algorithms of the Qbox and WEST codes and to develop a road-map for further development targeting next-generation computing architectures. In particular, the optimizations of the Qbox and WEST codes on the KNL platform will target efficient large-scale electronic structure calculations of nanostructured materials exhibiting complex structures and prediction of their electronic and thermal properties for use in solar and thermal energy conversion device. This work was supported by MICCoM, as part of Comp. Mats. Sci. Program funded by the U.S. DOE, Office of Sci., BES, MSE Division. This research used resources of the ALCF, which is a DOE Office of Sci. User Facility under Contract DE-AC02-06CH11357.

DFTBaby: A software package for non-adiabatic molecular dynamics simulations based on long-range corrected tight-binding TD-DFT(B)

NASA Astrophysics Data System (ADS)

Humeniuk, Alexander; Mitrić, Roland

2017-12-01

A software package, called DFTBaby, is published, which provides the electronic structure needed for running non-adiabatic molecular dynamics simulations at the level of tight-binding DFT. A long-range correction is incorporated to avoid spurious charge transfer states. Excited state energies, their analytic gradients and scalar non-adiabatic couplings are computed using tight-binding TD-DFT. These quantities are fed into a molecular dynamics code, which integrates Newton's equations of motion for the nuclei together with the electronic Schrödinger equation. Non-adiabatic effects are included by surface hopping. As an example, the program is applied to the optimization of excited states and non-adiabatic dynamics of polyfluorene. The python and Fortran source code is available at http://www.dftbaby.chemie.uni-wuerzburg.de.

Comparative analyses of structural features and scaffold diversity for purchasable compound libraries.

PubMed

Shang, Jun; Sun, Huiyong; Liu, Hui; Chen, Fu; Tian, Sheng; Pan, Peichen; Li, Dan; Kong, Dexin; Hou, Tingjun

2017-04-21

Large purchasable screening libraries of small molecules afforded by commercial vendors are indispensable sources for virtual screening (VS). Selecting an optimal screening library for a specific VS campaign is quite important to improve the success rates and avoid wasting resources in later experimental phases. Analysis of the structural features and molecular diversity for different screening libraries can provide valuable information to the decision making process when selecting screening libraries for VS. In this study, the structural features and scaffold diversity of eleven purchasable screening libraries and Traditional Chinese Medicine Compound Database (TCMCD) were analyzed and compared. Their scaffold diversity represented by the Murcko frameworks and Level 1 scaffolds was characterized by the scaffold counts and cumulative scaffold frequency plots, and visualized by Tree Maps and SAR Maps. The analysis demonstrates that, based on the standardized subsets with similar molecular weight distributions, Chembridge, ChemicalBlock, Mucle, TCMCD and VitasM are more structurally diverse than the others. Compared with all purchasable screening libraries, TCMCD has the highest structural complexity indeed but more conservative molecular scaffolds. Moreover, we found that some representative scaffolds were important components of drug candidates against different drug targets, such as kinases and guanosine-binding protein coupled receptors, and therefore the molecules containing pharmacologically important scaffolds found in screening libraries might be potential inhibitors against the relevant targets. This study may provide valuable perspective on which purchasable compound libraries are better for you to screen. Graphical abstract Selecting diverse compound libraries with scaffold analyses.

Effect of thermal treatment on potato starch evidenced by EPR, XRD and molecular weight distribution.

PubMed

Bidzińska, Ewa; Michalec, Marek; Pawcenis, Dominika

2015-12-01

Effect of heating of the potato starch on damages of its structure was investigated by quantitative electron paramagnetic resonance (EPR) spectroscopy, X-ray diffraction and determination of the molecular weight distribution. The measurements were performed in the temperature range commonly used for starch modifications optimizing properties important for industrial applications. Upon thermal treatment, because of breaking of the polymer chains, diminishing of the average molecular weights occurred, which significantly influences generation of radicals, evidenced by EPR. For the relatively mild conditions, with heating parameters not exceeding temperature 230 °C and time of heating equal to 30 min a moderate changes of both the number of thermally generated radicals and the mean molecular weight of the starch were observed. After more drastic thermal treatment (e.g. 2 h at 230 °C), a rapid increase in the radical amount occurred, which was accompanied by significant reduction of the starch molecular size and crystallinity. Experimentally established threshold values of heating parameters should not be exceeded in order to avoid excessive damages of the starch structure accompanied by the formation of the redundant amount of radicals. This requirement is important for industrial applications, because significant destruction of the starch matrix might annihilate the positive influence of the previously performed intentional starch modification. Copyright © 2015 John Wiley & Sons, Ltd.

The Molecular Structure of a Phosphatidylserine Bilayer Determined by Scattering and Molecular Dynamics Simulations

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

Pan, Jianjun; Cheng, Xiaolin; Monticelli, Luca

2014-01-01

Phosphatidylserine (PS) lipids play essential roles in biological processes, including enzyme activation and apoptosis. We report on the molecular structure and atomic scale interactions of a fluid bilayer composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS). A scattering density profile model, aided by molecular dynamics (MD) simulations, was developed to jointly refine different contrast small-angle neutron and X-ray scattering data, which yielded a lipid area of 62.7 A2 at 25 C. MD simulations with POPS lipid area constrained at different values were also performed using all-atom and aliphatic united-atom models. The optimal simulated bilayer was obtained using a model-free comparison approach. Examination of themore » simulated bilayer, which agrees best with the experimental scattering data, reveals a preferential interaction between Na+ ions and the terminal serine and phosphate moieties. Long-range inter-lipid interactions were identified, primarily between the positively charged ammonium, and the negatively charged carboxylic and phosphate oxygens. The area compressibility modulus KA of the POPS bilayer was derived by quantifying lipid area as a function of surface tension from area-constrained MD simulations. It was found that POPS bilayers possess a much larger KA than that of neutral phosphatidylcholine lipid bilayers. We propose that the unique molecular features of POPS bilayers may play an important role in certain physiological functions.« less

Targeting blood–brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery

PubMed Central

Ronaldson, Patrick T; Davis, Thomas P

2012-01-01

The blood–brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery. PMID:22468221

Photoluminescence and Band Alignment of Strained GaAsSb/GaAs QW Structures Grown by MBE on GaAs

PubMed Central

Sadofyev, Yuri G.; Samal, Nigamananda

2010-01-01

An in-depth optimization of growth conditions and investigation of optical properties including discussions on band alignment of GaAsSb/GaAs quantum well (QW) on GaAs by molecular beam epitaxy (MBE) are reported. Optimal MBE growth temperature of GaAsSb QW is found to be 470 ± 10 °C. GaAsSb/GaAs QW with Sb content ~0.36 has a weak type-II band alignment with valence band offset ratio QV ~1.06. A full width at half maximum (FWHM) of ~60 meV in room temperature (RT) photoluminescence (PL) indicates fluctuation in electrostatic potential to be less than 20 meV. Samples grown under optimal conditions do not exhibit any blue shift of peak in RT PL spectra under varying excitation.

E-novo: an automated workflow for efficient structure-based lead optimization.

PubMed

Pearce, Bradley C; Langley, David R; Kang, Jia; Huang, Hongwei; Kulkarni, Amit

2009-07-01

An automated E-Novo protocol designed as a structure-based lead optimization tool was prepared through Pipeline Pilot with existing CHARMm components in Discovery Studio. A scaffold core having 3D binding coordinates of interest is generated from a ligand-bound protein structural model. Ligands of interest are generated from the scaffold using an R-group fragmentation/enumeration tool within E-Novo, with their cores aligned. The ligand side chains are conformationally sampled and are subjected to core-constrained protein docking, using a modified CHARMm-based CDOCKER method to generate top poses along with CDOCKER energies. In the final stage of E-Novo, a physics-based binding energy scoring function ranks the top ligand CDOCKER poses using a more accurate Molecular Mechanics-Generalized Born with Surface Area method. Correlation of the calculated ligand binding energies with experimental binding affinities were used to validate protocol performance. Inhibitors of Src tyrosine kinase, CDK2 kinase, beta-secretase, factor Xa, HIV protease, and thrombin were used to test the protocol using published ligand crystal structure data within reasonably defined binding sites. In-house Respiratory Syncytial Virus inhibitor data were used as a more challenging test set using a hand-built binding model. Least squares fits for all data sets suggested reasonable validation of the protocol within the context of observed ligand binding poses. The E-Novo protocol provides a convenient all-in-one structure-based design process for rapid assessment and scoring of lead optimization libraries.

Selecting an optimal number of binding site waters to improve virtual screening enrichments against the adenosine A2A receptor.

PubMed

Lenselink, Eelke B; Beuming, Thijs; Sherman, Woody; van Vlijmen, Herman W T; IJzerman, Adriaan P

2014-06-23

A major challenge in structure-based virtual screening (VS) involves the treatment of explicit water molecules during docking in order to improve the enrichment of active compounds over decoys. Here we have investigated this in the context of the adenosine A2A receptor, where water molecules have previously been shown to be important for achieving high enrichment rates with docking, and where the positions of some binding site waters are known from a high-resolution crystal structure. The effect of these waters (both their presence and orientations) on VS enrichment was assessed using a carefully curated set of 299 high affinity A2A antagonists and 17,337 decoys. We show that including certain crystal waters greatly improves VS enrichment and that optimization of water hydrogen positions is needed in order to achieve the best results. We also show that waters derived from a molecular dynamics simulation - without any knowledge of crystallographic waters - can improve enrichments to a similar degree as the crystallographic waters, which makes this strategy applicable to structures without experimental knowledge of water positions. Finally, we used decision trees to select an ensemble of structures with different water molecule positions and orientations that outperforms any single structure with water molecules. The approach presented here is validated against independent test sets of A2A receptor antagonists and decoys from the literature. In general, this water optimization strategy could be applied to any target with waters-mediated protein-ligand interactions.

Spectroscopic characteristic (FT-IR, FT-Raman, UV, 1H and 13C NMR), theoretical calculations and biological activity of alkali metal homovanillates

NASA Astrophysics Data System (ADS)

Samsonowicz, M.; Kowczyk-Sadowy, M.; Piekut, J.; Regulska, E.; Lewandowski, W.

2016-04-01

The structural and vibrational properties of lithium, sodium, potassium, rubidium and cesium homovanillates were investigated in this paper. Supplementary molecular spectroscopic methods such as: FT-IR, FT-Raman in the solid phase, UV and NMR were applied. The geometrical parameters and energies were obtained from density functional theory (DFT) B3LYP method with 6-311++G** basis set calculations. The geometry of the molecule was fully optimized, vibrational spectra were calculated and fundamental vibrations were assigned. Geometric and magnetic aromaticity indices, atomic charges, dipole moments, HOMO and LUMO energies were also calculated. The microbial activity of investigated compounds was tested against Bacillus subtilis (BS), Pseudomonas aeruginosa (PA), Escherichia coli (EC), Staphylococcus aureus (SA) and Candida albicans (CA). The relationship between the molecular structure of tested compounds and their antimicrobial activity was studied. The principal component analysis (PCA) was applied in order to attempt to distinguish the biological activities of these compounds according to selected band wavenumbers. Obtained data show that the FT-IR spectra can be a rapid and reliable analytical tool and a good source of information for the quantitative analysis of the relationship between the molecular structure of the compound and its biological activity.

Docking, thermodynamics and molecular dynamics (MD) studies of a non-canonical protease inhibitor, MP-4, from Mucuna pruriens.

PubMed

Kumar, Ashish; Kaur, Harmeet; Jain, Abha; Nair, Deepak T; Salunke, Dinakar M

2018-01-12

Sequence and structural homology suggests that MP-4 protein from Mucuna pruriens belongs to Kunitz-type protease inhibitor family. However, biochemical assays showed that this protein is a poor inhibitor of trypsin. To understand the basis of observed poor inhibition, thermodynamics and molecular dynamics (MD) simulation studies on binding of MP-4 to trypsin were carried out. Molecular dynamics simulations revealed that temperature influences the spectrum of conformations adopted by the loop regions in the MP-4 structure. At an optimal temperature, MP-4 achieves maximal binding while above and below the optimum temperature, its functional activity is hampered due to unfavourable flexibility and relative rigidity, respectively. The low activity at normal temperature is due to the widening of the conformational spectrum of the Reactive Site Loop (RSL) that reduces the probability of formation of stabilizing contacts with trypsin. The unique sequence of the RSL enhances flexibility at ambient temperature and thus reduces its ability to inhibit trypsin. This study shows that temperature influences the function of a protein through modulation in the structure of functional domain of the protein. Modulation of function through appearance of new sequences that are more sensitive to temperature may be a general strategy for evolution of new proteins.

Thermally stable solids based on endohedrally doped ZnS clusters.

PubMed

Matxain, Jon M; Piris, Mario; Lopez, Xabier; Ugalde, Jesus M

2009-01-01

The existence of inorganic, hollow, fullerene-like ZnS clusters has been theoretically predicted and then recently confirmed experimentally. These clusters were observed to trap alkali metals and halogens because the ionization energies (IE) of alkali metals are very similar to the electron affinities (EA) of halogens. This opens the possibility of forming molecular solids composed of these fullerene building blocks because the energy released due to the difference between the IE and EA would be very small. Herein we have focused on assembling bare Zn(12)S(12) and endohedral X@Zn(12)S(12)-Y@Zn(12)S(12) dimers (X = Na, K; Y = Cl, Br) by considering the square-faces-square orientation of every two adjacent clusters, which leads to a fcc cubic crystal structure in the solid. The structures were fully optimized in all cases, and their thermal stability was confirmed by ab initio thermal molecular dynamics calculations. The optimum lattice parameter of the solids was found to be around 13.8 A, which corresponds to distances of about 2.5 A between monomers, which is typical of covalent Zn-S bonds. The resulting solids are nanoporous materials similar to B(12)N(12). Due to their nanoporous structure, these zeolite-shaped solids could be used in heterogeneous catalysis and as storage materials and molecular sieves.

Discovery of novel human acrosin inhibitors by virtual screening

NASA Astrophysics Data System (ADS)

Liu, Xuefei; Dong, Guoqiang; Zhang, Jue; Qi, Jingjing; Zheng, Canhui; Zhou, Youjun; Zhu, Ju; Sheng, Chunquan; Lü, Jiaguo

2011-10-01

Human acrosin is an attractive target for the discovery of male contraceptive drugs. For the first time, structure-based drug design was applied to discover structurally diverse human acrosin inhibitors. A parallel virtual screening strategy in combination with pharmacophore-based and docking-based techniques was used to screen the SPECS database. From 16 compounds selected by virtual screening, a total of 10 compounds were found to be human acrosin inhibitors. Compound 2 was found to be the most potent hit (IC50 = 14 μM) and its binding mode was investigated by molecular dynamics simulations. The hit interacted with human acrosin mainly through hydrophobic and hydrogen-bonding interactions, which provided a good starting structure for further optimization studies.

Band Structure Simulations of the Photoinduced Changes in the MgB₂:Cr Films.

PubMed

Kityk, Iwan V; Fedorchuk, Anatolii O; Ozga, Katarzyna; AlZayed, Nasser S

2015-04-02

An approach for description of the photoinduced nonlinear optical effects in the superconducting MgB₂:Cr₂O₃ nanocrystalline film is proposed. It includes the molecular dynamics step-by-step optimization of the two separate crystalline phases. The principal role for the photoinduced nonlinear optical properties plays nanointerface between the two phases. The first modified layers possess a form of slightly modified perfect crystalline structure. The next layer is added to the perfect crystalline structure and the iteration procedure is repeated for the next layer. The total energy here is considered as a varied parameter. To avoid potential jumps on the borders we have carried out additional derivative procedure.

Universal optimal working cycles of molecular motors.

PubMed

Efremov, Artem; Wang, Zhisong

2011-04-07

Molecular motors capable of directional track-walking or rotation are abundant in living cells, and inspire the emerging field of artificial nanomotors. Some biomotors can convert 90% of free energy from chemical fuels into usable mechanical work, and the same motors still maintain a speed sufficient for cellular functions. This study exposed a new regime of universal optimization that amounts to a thermodynamically best working regime for molecular motors but is unfamiliar in macroscopic engines. For the ideal case of zero energy dissipation, the universally optimized working cycle for molecular motors is infinitely slow like Carnot cycle for heat engines. But when a small amount of energy dissipation reduces energy efficiency linearly from 100%, the speed is recovered exponentially due to Boltzmann's law. Experimental data on a major biomotor (kinesin) suggest that the regime of universal optimization has been largely approached in living cells, underpinning the extreme efficiency-speed trade-off in biomotors. The universal optimization and its practical approachability are unique thermodynamic advantages of molecular systems over macroscopic engines in facilitating motor functions. The findings have important implications for the natural evolution of biomotors as well as the development of artificial counterparts.

Sequential Injection Analysis for Optimization of Molecular Biology Reactions

PubMed Central

Allen, Peter B.; Ellington, Andrew D.

2011-01-01

In order to automate the optimization of complex biochemical and molecular biology reactions, we developed a Sequential Injection Analysis (SIA) device and combined this with a Design of Experiment (DOE) algorithm. This combination of hardware and software automatically explores the parameter space of the reaction and provides continuous feedback for optimizing reaction conditions. As an example, we optimized the endonuclease digest of a fluorogenic substrate, and showed that the optimized reaction conditions also applied to the digest of the substrate outside of the device, and to the digest of a plasmid. The sequential technique quickly arrived at optimized reaction conditions with less reagent use than a batch process (such as a fluid handling robot exploring multiple reaction conditions in parallel) would have. The device and method should now be amenable to much more complex molecular biology reactions whose variable spaces are correspondingly larger. PMID:21338059

Molecular structure, second- and third-order nonlinear optical properties and DFT studies of a novel non-centrosymmetric chalcone derivative: (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl)methylene]amino}phenyl)prop-2-en-1-one

NASA Astrophysics Data System (ADS)

Maidur, Shivaraj R.; Patil, Parutagouda Shankaragouda; Ekbote, Anusha; Chia, Tze Shyang; Quah, Ching Kheng

2017-09-01

In the present work, the title chalcone, (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl) methylene]amino}phenyl)prop-2-en-1-one (abbreviated as FAMFC), was synthesized and structurally characterized by single-crystal X-ray diffraction. The compound is crystallized in the monoclinic system with non-centrosymmetric space group P21 and hence it satisfies the essential condition for materials to exhibit second-order nonlinear optical properties. The molecular structure was further confirmed by using FT-IR and 1H NMR spectroscopic techniques. The title crystal is transparent in the Vis-NIR region and has a direct band gap. The third-order nonlinear optical properties were investigated in solution (0.01 M) by Z-scan technique using a continuous wave (CW) DPSS laser at the wavelength of 532 nm. The title chalcone exhibited significant two-photon absorption (β = 35.8 × 10- 5 cm W- 1), negative nonlinear refraction (n2 = - 0.18 × 10- 8 cm2 W- 1) and optical limiting (OL threshold = 2.73 kJ cm- 2) under the CW regime. In support of the experimental results, a comprehensive theoretical study was carried out on the molecule of FAMFC using density functional theory (DFT). The optimized geometries and frontier molecular orbitals were calculated by employing B3LYP/6-31 + G level of theory. The optimized molecular structure was confirmed computationally by IR vibrational and 1H NMR spectral analysis. The experimental UV-Vis-NIR spectrum was interpreted using computational chemistry under time-dependent DFT. The static and dynamic NLO properties such as dipole moments (μ), polarizability (α), and first hyperpolarizabilities (β) were computed by using finite field method. The obtained dynamic first hyperpolarizability β(- 2ω;ω,ω) at input frequency ω = 0.04282 a.u. is predicted to be 161 times higher than urea standard. The electronic excitation energies and HOMO-LUMO band gap for FAMFC were also evaluated by DFT. The experimental and theoretical results are in good agreement, and the NLO study suggests that FAMFC molecule can be a potential candidate in the nonlinear optical applications.

Molecular structure, second- and third-order nonlinear optical properties and DFT studies of a novel non-centrosymmetric chalcone derivative: (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl)methylene]amino}phenyl)prop-2-en-1-one.

PubMed

Maidur, Shivaraj R; Patil, Parutagouda Shankaragouda; Ekbote, Anusha; Chia, Tze Shyang; Quah, Ching Kheng

2017-09-05

In the present work, the title chalcone, (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl) methylene]amino}phenyl)prop-2-en-1-one (abbreviated as FAMFC), was synthesized and structurally characterized by single-crystal X-ray diffraction. The compound is crystallized in the monoclinic system with non-centrosymmetric space group P2 1 and hence it satisfies the essential condition for materials to exhibit second-order nonlinear optical properties. The molecular structure was further confirmed by using FT-IR and 1 H NMR spectroscopic techniques. The title crystal is transparent in the Vis-NIR region and has a direct band gap. The third-order nonlinear optical properties were investigated in solution (0.01M) by Z-scan technique using a continuous wave (CW) DPSS laser at the wavelength of 532nm. The title chalcone exhibited significant two-photon absorption (β=35.8×10 -5 cmW -1 ), negative nonlinear refraction (n 2 =-0.18×10 -8 cm 2 W -1 ) and optical limiting (OL threshold=2.73kJcm -2 ) under the CW regime. In support of the experimental results, a comprehensive theoretical study was carried out on the molecule of FAMFC using density functional theory (DFT). The optimized geometries and frontier molecular orbitals were calculated by employing B3LYP/6-31+G level of theory. The optimized molecular structure was confirmed computationally by IR vibrational and 1 H NMR spectral analysis. The experimental UV-Vis-NIR spectrum was interpreted using computational chemistry under time-dependent DFT. The static and dynamic NLO properties such as dipole moments (μ), polarizability (α), and first hyperpolarizabilities (β) were computed by using finite field method. The obtained dynamic first hyperpolarizability β(-2ω;ω,ω) at input frequency ω=0.04282a.u. is predicted to be 161 times higher than urea standard. The electronic excitation energies and HOMO-LUMO band gap for FAMFC were also evaluated by DFT. The experimental and theoretical results are in good agreement, and the NLO study suggests that FAMFC molecule can be a potential candidate in the nonlinear optical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Constant pH Accelerated Molecular Dynamics Investigation of the pH Regulation Mechanism of Dinoflagellate Luciferase.

PubMed

Donnan, Patrick H; Ngo, Phong D; Mansoorabadi, Steven O

2018-01-23

The bioluminescence reaction in dinoflagellates involves the oxidation of an open-chain tetrapyrrole by the enzyme dinoflagellate luciferase (LCF). The activity of LCF is tightly regulated by pH, where the enzyme is essentially inactive at pH ∼8 and optimally active at pH ∼6. Little is known about the mechanism of LCF or the structure of the active form of the enzyme, although it has been proposed that several intramolecularly conserved histidine residues in the N-terminal region are important for the pH regulation mechanism. Here, constant pH accelerated molecular dynamics was employed to gain insight into the conformational activation of LCF induced by acidification.

Electrospinning bioactive supramolecular polymers from water.

PubMed

Tayi, Alok S; Pashuck, E Thomas; Newcomb, Christina J; McClendon, Mark T; Stupp, Samuel I

2014-04-14

Electrospinning is a high-throughput, low-cost technique for manufacturing long fibers from solution. Conventionally, this technique is used with covalent polymers with large molecular weights. We report here the electrospinning of functional peptide-based supramolecular polymers from water at very low concentrations (<4 wt %). Molecules with low molecular weights (<1 kDa) could be electrospun because they self-assembled into one-dimensional supramolecular polymers upon solvation and the critical parameters of viscosity, solution conductivity, and surface tension were optimized for this technique. The supramolecular structure of the electrospun fibers could ensure that certain residues, like bioepitopes, are displayed on the surface even after processing. This system provides an opportunity to electrospin bioactive supramolecular materials from water for biomedical applications.

ReaxFF molecular dynamics simulation of intermolecular structure formation in acetic acid-water mixtures at elevated temperatures and pressures

NASA Astrophysics Data System (ADS)

Sengul, Mert Y.; Randall, Clive A.; van Duin, Adri C. T.

2018-04-01

The intermolecular structure formation in liquid and supercritical acetic acid-water mixtures was investigated using ReaxFF-based molecular dynamics simulations. The microscopic structures of acetic acid-water mixtures with different acetic acid mole fractions (1.0 ≥ xHAc ≥ 0.2) at ambient and critical conditions were examined. The potential energy surface associated with the dissociation of acetic acid molecules was calculated using a metadynamics procedure to optimize the dissociation energy of ReaxFF potential. At ambient conditions, depending on the acetic acid concentration, either acetic acid clusters or water clusters are dominant in the liquid mixture. When acetic acid is dominant (0.4 ≤ xHAc), cyclic dimers and chain structures between acetic acid molecules are present in the mixture. Both structures disappear at increased water content of the mixture. It was found by simulations that the acetic acid molecules released from these dimer and chain structures tend to stay in a dipole-dipole interaction. These structural changes are in agreement with the experimental results. When switched to critical conditions, the long-range interactions (e.g., second or fourth neighbor) disappear and the water-water and acetic acid-acetic acid structural formations become disordered. The simulated radial distribution function for water-water interactions is in agreement with experimental and computational studies. The first neighbor interactions between acetic acid and water molecules are preserved at relatively lower temperatures of the critical region. As higher temperatures are reached in the critical region, these interactions were observed to weaken. These simulations indicate that ReaxFF molecular dynamics simulations are an appropriate tool for studying supercritical water/organic acid mixtures.

Blockade of Nociceptin Signaling Reduces Biochemical, Structural and Cognitive Deficits after Traumatic Brain Injury

DTIC Science & Technology

2010-07-01

also will determine if ORL1 antagonists block downstream gene transcription subsequent to enzyme activation. BODY: Task 1a was to optimize blast...value between 60 and 80 psi at which defects in vestibulomotor function can be detected. These findings could potentially become a clinical...nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a molecular mechanism for

Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis.

PubMed

Martínez, Leandro

2015-01-01

The analysis of structural mobility in molecular dynamics plays a key role in data interpretation, particularly in the simulation of biomolecules. The most common mobility measures computed from simulations are the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuations (RMSF) of the structures. These are computed after the alignment of atomic coordinates in each trajectory step to a reference structure. This rigid-body alignment is not robust, in the sense that if a small portion of the structure is highly mobile, the RMSD and RMSF increase for all atoms, resulting possibly in poor quantification of the structural fluctuations and, often, to overlooking important fluctuations associated to biological function. The motivation of this work is to provide a robust measure of structural mobility that is practical, and easy to interpret. We propose a Low-Order-Value-Optimization (LOVO) strategy for the robust alignment of the least mobile substructures in a simulation. These substructures are automatically identified by the method. The algorithm consists of the iterative superposition of the fraction of structure displaying the smallest displacements. Therefore, the least mobile substructures are identified, providing a clearer picture of the overall structural fluctuations. Examples are given to illustrate the interpretative advantages of this strategy. The software for performing the alignments was named MDLovoFit and it is available as free-software at: http://leandro.iqm.unicamp.br/mdlovofit.

Automatic Identification of Mobile and Rigid Substructures in Molecular Dynamics Simulations and Fractional Structural Fluctuation Analysis

PubMed Central

Martínez, Leandro

2015-01-01

The analysis of structural mobility in molecular dynamics plays a key role in data interpretation, particularly in the simulation of biomolecules. The most common mobility measures computed from simulations are the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuations (RMSF) of the structures. These are computed after the alignment of atomic coordinates in each trajectory step to a reference structure. This rigid-body alignment is not robust, in the sense that if a small portion of the structure is highly mobile, the RMSD and RMSF increase for all atoms, resulting possibly in poor quantification of the structural fluctuations and, often, to overlooking important fluctuations associated to biological function. The motivation of this work is to provide a robust measure of structural mobility that is practical, and easy to interpret. We propose a Low-Order-Value-Optimization (LOVO) strategy for the robust alignment of the least mobile substructures in a simulation. These substructures are automatically identified by the method. The algorithm consists of the iterative superposition of the fraction of structure displaying the smallest displacements. Therefore, the least mobile substructures are identified, providing a clearer picture of the overall structural fluctuations. Examples are given to illustrate the interpretative advantages of this strategy. The software for performing the alignments was named MDLovoFit and it is available as free-software at: http://leandro.iqm.unicamp.br/mdlovofit PMID:25816325

Molecular structure, NMR, UV-Visible, vibrational spectroscopic and HOMO, LUMO analysis of (E)-1-(2, 6-bis (4-methoxyphenyl)-3, 3-dimethylpiperidine-4-ylidene)-2-(3-(3, 5-dimethyl-1H-pyrazol-1-yl) pyrazin-2-yl) hydrazine by DFT method

NASA Astrophysics Data System (ADS)

Alphonsa, A. Therasa; Loganathan, C.; Anand, S. Athavan Alias; Kabilan, S.

2016-02-01

We have synthesized (E)-1-(2, 6-bis (4-methoxyphenyl)-3, 3-dimethylpiperidine-4-ylidene)-2-(3-(3, 5-dimethyl-1H-pyrazol-1-yl) pyrazin-2-yl) hydrazine (PM6). It was characterized using FT-IR, FT-Raman, 1H NMR, 13C NMR techniques. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 09 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-311 G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated stretching frequencies have been found to be in good agreement with the experimental frequencies. The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and density of states (DOS). The absorption spectra have been computed by using time dependent density functional theory (TD-DFT). 1H and 13C NMR spectra were recorded and 1H and 13C NMR chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. From the optimized geometry of the molecule, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMOs) of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values.

Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory

NASA Astrophysics Data System (ADS)

Mrugalla, Florian; Kast, Stefan M.

2016-09-01

Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory.

PubMed

Mrugalla, Florian; Kast, Stefan M

2016-09-01

Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

A structural perspective on the interactions of TRAF6 and Basigin during the onset of melanoma: A molecular dynamics simulation study.

PubMed

Biswas, Ria; Ghosh, Semanti; Bagchi, Angshuman

2017-11-01

Metastatic melanoma is the most fatal type of skin cancer. The roles of matrix metalloproteinases (MMPs) have well been established in the onset of melanoma. Basigin (BSG) belongs to the immunoglobulin superfamily and is critical for induction of extracellular MMPs during the onset of various cancers including melanoma. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3-ligase that interacts with BSG and mediates its membrane localization, which leads to MMP expression in melanoma cells. This makes TRAF6 a potential therapeutic target in melanoma. We here conducted protein-protein interaction studies on TRAF6 and BSG to get molecular level insights of the reactions. The structure of human BSG was constructed by protein threading. Molecular-docking method was applied to develop the TRAF6-BSG complex. The refined docked complex was further optimized by molecular dynamics simulations. Results from binding free energy, surface properties, and electrostatic interaction analysis indicate that Lys340 and Glu417 of TRAF6 play as the anchor residues in the protein interaction interface. The current study will be helpful in designing specific modulators of TRAF6 to control melanoma metastasis. Copyright © 2017 John Wiley & Sons, Ltd.

N-(4-Nitrobenzoyl)-N'-(1,5-dimethyl-3-oxo-2-phenyl-1H-3(2H)-pyrazolyl)-thiourea hydrate: Synthesis, spectroscopic characterization, X-ray structure and DFT studies

NASA Astrophysics Data System (ADS)

Arslan, N. Burcu; Kazak, Canan; Aydın, Fatma

2012-04-01

The title molecule (C19H17N5O4S·H2O) was synthesized and characterized by IR-NMR spectroscopy, MS and single-crystal X-ray diffraction. The molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) 1H and 13C NMR chemical shift values of the compound in the ground state have been calculated by using the density functional theory (DFT) method with 6-31G(d) basis set, and compared with the experimental data. All the assignments of the theoretical frequencies were performed by potential energy distributions using VEDA 4 program. The calculated results show that the optimized geometries can well reproduce the crystal structural parameters, and the theoretical vibrational frequencies and 1H and 13C NMR chemical shift values show good agreement with experimental data. To determine conformational flexibility, the molecular energy profile of the title compound was obtained with respect to the selected torsion angle, which was varied from -180° to +180° in steps of 10°. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis and thermodynamic properties of the compound were investigated by theoretical calculations.

Spectroscopic investigation, vibrational assignments, HOMO-LUMO, NBO, MEP analysis and molecular docking studies of oxoaporphine alkaloid liriodenine

NASA Astrophysics Data System (ADS)

Costa, Renyer A.; Pitt, Priscilla Olliveira; Pinheiro, Maria Lucia B.; Oliveira, Kelson M. T.; Salomé, Kahlil Schwanka; Barison, Andersson; Costa, Emmanoel Vilaça

2017-03-01

A combined experimental and theoretical DFT study of the structural, vibrational and electronic properties of liriodenine is presented using B3LYP function with 6-311G (2d, p) basis set. The theoretical geometry optimization data were compared with the X-ray data for a similar structure in the associated literature, showing similar values. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap, mapped molecular Electrostatic Potential (MEP) surface calculation, first and second order hyperpolarizabilities were also performed with the same calculation level. Theoretical UV spectrum agreed well with the measured experimental data, with transitions assigned. The molecular electrostatic potential map shows opposite potentials regions that forms hydrogen bonds that stabilize the dimeric form, which were confirmed by the close values related to the C dbnd O bond stretching between the dimeric form and the experimental IR spectra (1654 cm- 1 for the experimental, 1700 cm- 1 for the dimer form). Calculated HOMO/LUMO gaps shows the excitation energy for Liriodenine, justifying its stability and kinetics reaction. Molecular docking studies with Candida albicans dihydrofolate reductase (DHFR) and Candida albicans secreted aspartic protease (SAP) showed binding free energies values of - 8.5 and - 8.3 kcal/mol, suggesting good affinity between the liriodenine and the target macromolecules.

QSAR, molecular docking studies of thiophene and imidazopyridine derivatives as polo-like kinase 1 inhibitors

NASA Astrophysics Data System (ADS)

Cao, Shandong

2012-08-01

The purpose of the present study was to develop in silico models allowing for a reliable prediction of polo-like kinase inhibitors based on a large diverse dataset of 136 compounds. As an effective method, quantitative structure activity relationship (QSAR) was applied using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The proposed QSAR models showed reasonable predictivity of thiophene analogs (Rcv2=0.533, Rpred2=0.845) and included four molecular descriptors, namely IC3, RDF075m, Mor02m and R4e+. The optimal model for imidazopyridine derivatives (Rcv2=0.776, Rpred2=0.876) was shown to perform good in prediction accuracy, using GATS2m and BEHe1 descriptors. Analysis of the contour maps helped to identify structural requirements for the inhibitors and served as a basis for the design of the next generation of the inhibitor analogues. Docking studies were also employed to position the inhibitors into the polo-like kinase active site to determine the most probable binding mode. These studies may help to understand the factors influencing the binding affinity of chemicals and to develop alternative methods for prescreening and designing of polo-like kinase inhibitors.

How PEGylation enhances the stability and potency of insulin: a molecular dynamics simulation.

PubMed

Yang, Cheng; Lu, Diannan; Liu, Zheng

2011-04-05

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications.

Meeting Report: Structural Determination of Environmentally Responsive Proteins

PubMed Central

Reinlib, Leslie

2005-01-01

The three-dimensional structure of gene products continues to be a missing lynchpin between linear genome sequences and our understanding of the normal and abnormal function of proteins and pathways. Enhanced activity in this area is likely to lead to better understanding of how discrete changes in molecular patterns and conformation underlie functional changes in protein complexes and, with it, sensitivity of an individual to an exposure. The National Institute of Environmental Health Sciences convened a workshop of experts in structural determination and environmental health to solicit advice for future research in structural resolution relative to environmentally responsive proteins and pathways. The highest priorities recommended by the workshop were to support studies of structure, analysis, control, and design of conformational and functional states at molecular resolution for environmentally responsive molecules and complexes; promote understanding of dynamics, kinetics, and ligand responses; investigate the mechanisms and steps in posttranslational modifications, protein partnering, impact of genetic polymorphisms on structure/function, and ligand interactions; and encourage integrated experimental and computational approaches. The workshop participants also saw value in improving the throughput and purity of protein samples and macromolecular assemblies; developing optimal processes for design, production, and assembly of macromolecular complexes; encouraging studies on protein–protein and macromolecular interactions; and examining assemblies of individual proteins and their functions in pathways of interest for environmental health. PMID:16263521

Structural and spectral analyses of N,N'-(2,2'-dithiodi-o-phenylene)bis-(furan-2-carboxamide)

NASA Astrophysics Data System (ADS)

Yıldırım, Sema Öztürk; Büyükmumcu, Zeki; Pekdur, Özlem Savaş; Butcher, Ray J.; Doǧan, Şengül Dilem

2018-02-01

In this study we report structure determination of N,N'-(2,2'-dithiodi-o-phenylene)bis-(furan-2-carboxamide). 2,2'-Dithiobis(benzamide) derivatives have been reported to possess important biological properties such as antibacterial, antifungal activities and inhibition of blood platelet aggregation and redeterrmined at 100(2)K from the data published by Raftery, Lallbeeharry, Bhowon, Laulloo & Joulea [Acta Cryst. 2009, E65, o16]. 2,2'-Dithiobis(N-butyl-benzamide) has been reported to be useful as an antiseptic for cosmetics. The structural properties of the compound have been characterized by using 1H NMR and the structure were determined by single-crystal X-ray diffraction. Molecular structure crystallizes in triclinic form, space group with a = 9.6396(7) Å, b = 9.9115(7) Å, c = 12.0026(8) Å, α = 109.743(6)°, β = 103.653(6)°, γ = 104.633(6)° and V = 977.15(13) Å3. In the solid state of the molecular structure N-H…S, N-H…O and C-H…O, type interactions provide for stabilization. The geometries of the title compound have been optimized using density functional theory (DFT) method. The calculated values were found to be in agreement with the experimental data.

Accurate optimization of amino acid form factors for computing small-angle X-ray scattering intensity of atomistic protein structures

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

Tong, Dudu; Yang, Sichun; Lu, Lanyuan

2016-06-20

Structure modellingviasmall-angle X-ray scattering (SAXS) data generally requires intensive computations of scattering intensity from any given biomolecular structure, where the accurate evaluation of SAXS profiles using coarse-grained (CG) methods is vital to improve computational efficiency. To date, most CG SAXS computing methods have been based on a single-bead-per-residue approximation but have neglected structural correlations between amino acids. To improve the accuracy of scattering calculations, accurate CG form factors of amino acids are now derived using a rigorous optimization strategy, termed electron-density matching (EDM), to best fit electron-density distributions of protein structures. This EDM method is compared with and tested againstmore » other CG SAXS computing methods, and the resulting CG SAXS profiles from EDM agree better with all-atom theoretical SAXS data. By including the protein hydration shell represented by explicit CG water molecules and the correction of protein excluded volume, the developed CG form factors also reproduce the selected experimental SAXS profiles with very small deviations. Taken together, these EDM-derived CG form factors present an accurate and efficient computational approach for SAXS computing, especially when higher molecular details (represented by theqrange of the SAXS data) become necessary for effective structure modelling.« less

Preparation and evaluation of posaconazole-loaded enteric microparticles in rats.

PubMed

Yang, Min; Dong, Zhonghua; Zhang, Yongchun; Zhang, Fang; Wang, Yongjie; Zhao, Zhongxi

2017-04-01

Posaconazole (POS) is an antifungal compound which has a low oral bioavailability. The aim of this study was to prepare POS enteric microparticles to enhance its oral bioavailability. POS enteric microparticles were prepared with hypromellose acetate succinate (HPMCAS) via the spray drying method. The solvent mixtures of acetone and ethanol used in the preparation of the microparticles were optimized to produce the ideal POS enteric microparticles. Multivariate data analysis using a principal component analysis (PCA) was used to find the relationship among the HPMCAS molecular characteristics, particle properties and drug release kinetics from the spray dried microparticles. The optimal spray solvent mixtures were critical to produce the POS microparticles with the defined polymer entanglement index, drug surface enrichment, particle size and drug loading. The HPMCAS molecular characteristics affected the microscopic connectivity and diffusivity of polymer matrix and eventually influenced the drug release behavior, and enhanced the bioavailability of POS. These studies suggested that the selection of suitable solvent mixtures of acetone and ethanol used in the spray drying of the microparticles was quite important to produce the entangled polymer structures with preferred polymer molecular properties of polymer coiling, overlap concentration and entanglement index. Additional studies on particle size and surface drug enrichment eventually produced HPMCAS-based enteric microparticles to enhance the oral bioavailability of POS.

Quantum mechanical, spectroscopic study (FT-IR and FT - Raman), NBO analysis, HOMO-LUMO, first order hyperpolarizability and docking studies of a non-steroidal anti-inflammatory compound

NASA Astrophysics Data System (ADS)

Sakthivel, S.; Alagesan, T.; Muthu, S.; Abraham, Christina Susan; Geetha, E.

2018-03-01

Experimental and theoretical studies on the optimized geometrical structure, electronic and vibrational characteristics of (+)-(S)-2-(6-methoxynaphthalen-2-yl) propanoic acid are presented employing B3LYP/6-311++G (d,p) basis set. Simulated FT-IR and FT-Raman spectra were in concurrence with the observed spectra attained in a spectral range of FT-IR (4000 - 400 cm-1) and FT-Raman (4000 - 100 cm-1). Quantum chemical calculations and the comprehensive vibrational assignments of wavenumbers of the optimized geometry using Potential Energy Distribution (PED) were calculated with scaled quantum mechanics. The infrared intensities and Raman intensities of (+)-(S)-2-(6-methoxynaphthalen-2-yl) propanoic acid were reported. Frontier molecular orbital analysis and reactivity parameters were calculated. Molecular Electrostatic Potential (MEP), Natural Bond Orbital (NBO) analysis, Non Linear Optical (NLO) behavior and thermodynamic properties were studied. In addition, the Mulliken charge distribution and Fukui function were analyzed. Molecular docking was used to dock in the title molecule into the active site of the protein 5L9B which belongs to the class of proteins exhibiting the property as a HIF1A (Hypoxia-inducible factor 1-alpha) expression inhibitor and the minimum binding energy was detected to be -6.2 kcal/mol.

Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability.

PubMed

Vieille, C; Zeikus, G J

2001-03-01

Enzymes synthesized by hyperthermophiles (bacteria and archaea with optimal growth temperatures of > 80 degrees C), also called hyperthermophilic enzymes, are typically thermostable (i.e., resistant to irreversible inactivation at high temperatures) and are optimally active at high temperatures. These enzymes share the same catalytic mechanisms with their mesophilic counterparts. When cloned and expressed in mesophilic hosts, hyperthermophilic enzymes usually retain their thermal properties, indicating that these properties are genetically encoded. Sequence alignments, amino acid content comparisons, crystal structure comparisons, and mutagenesis experiments indicate that hyperthermophilic enzymes are, indeed, very similar to their mesophilic homologues. No single mechanism is responsible for the remarkable stability of hyperthermophilic enzymes. Increased thermostability must be found, instead, in a small number of highly specific alterations that often do not obey any obvious traffic rules. After briefly discussing the diversity of hyperthermophilic organisms, this review concentrates on the remarkable thermostability of their enzymes. The biochemical and molecular properties of hyperthermophilic enzymes are described. Mechanisms responsible for protein inactivation are reviewed. The molecular mechanisms involved in protein thermostabilization are discussed, including ion pairs, hydrogen bonds, hydrophobic interactions, disulfide bridges, packing, decrease of the entropy of unfolding, and intersubunit interactions. Finally, current uses and potential applications of thermophilic and hyperthermophilic enzymes as research reagents and as catalysts for industrial processes are described.

Hyperthermophilic Enzymes: Sources, Uses, and Molecular Mechanisms for Thermostability

PubMed Central

Vieille, Claire; Zeikus, Gregory J.

2001-01-01

Enzymes synthesized by hyperthermophiles (bacteria and archaea with optimal growth temperatures of >80°C), also called hyperthermophilic enzymes, are typically thermostable (i.e., resistant to irreversible inactivation at high temperatures) and are optimally active at high temperatures. These enzymes share the same catalytic mechanisms with their mesophilic counterparts. When cloned and expressed in mesophilic hosts, hyperthermophilic enzymes usually retain their thermal properties, indicating that these properties are genetically encoded. Sequence alignments, amino acid content comparisons, crystal structure comparisons, and mutagenesis experiments indicate that hyperthermophilic enzymes are, indeed, very similar to their mesophilic homologues. No single mechanism is responsible for the remarkable stability of hyperthermophilic enzymes. Increased thermostability must be found, instead, in a small number of highly specific alterations that often do not obey any obvious traffic rules. After briefly discussing the diversity of hyperthermophilic organisms, this review concentrates on the remarkable thermostability of their enzymes. The biochemical and molecular properties of hyperthermophilic enzymes are described. Mechanisms responsible for protein inactivation are reviewed. The molecular mechanisms involved in protein thermostabilization are discussed, including ion pairs, hydrogen bonds, hydrophobic interactions, disulfide bridges, packing, decrease of the entropy of unfolding, and intersubunit interactions. Finally, current uses and potential applications of thermophilic and hyperthermophilic enzymes as research reagents and as catalysts for industrial processes are described. PMID:11238984

Transepithelial and endothelial transport of poly (amidoamine) dendrimers.

PubMed

Kitchens, Kelly M; El-Sayed, Mohamed E H; Ghandehari, Hamidreza

2005-12-14

This article summarizes our efforts to evaluate the potential of poly (amidoamine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the permeability of a series of cationic PAMAM-NH2 (G0-G4) dendrimers across Caco-2 cell monolayers was evaluated as a function of dendrimer generation, concentration, and incubation time. The influence of dendrimer surface charge on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers was monitored by measuring the transepithelial electrical resistance (TEER), 14C-mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. Microvascular extravasation of PAMAM-NH2 dendrimers in relation to their size, molecular weight, and molecular geometry is also discussed. Results of these studies show that transepithelial transport and microvascular extravasation of PAMAM dendrimers are dependent on their structural features including molecular size, molecular geometry, and surface chemistry. These results suggest that by optimizing the size and surface charge of PAMAM dendrimers, it is possible to develop oral delivery systems based on these carriers for targeted drug delivery.

Molecular Mechanism of Wide Photoabsorption Spectral Shifts of Color Variants of Human Cellular Retinol Binding Protein II.

PubMed

Cheng, Cheng; Kamiya, Motoshi; Uchida, Yoshihiro; Hayashi, Shigehiko

2015-10-21

Color variants of human cellular retinol binding protein II (hCRBPII) created by protein engineering were recently shown to exhibit anomalously wide photoabsorption spectral shifts over ∼200 nm across the visible region. The remarkable phenomenon provides a unique opportunity to gain insight into the molecular basis of the color tuning of retinal binding proteins for understanding of color vision as well as for engineering of novel color variants of retinal binding photoreceptor proteins employed in optogenetics. Here, we report a theoretical investigation of the molecular mechanism underlying the anomalously wide spectral shifts of the color variants of hCRBPII. Computational modeling of the color variants with hybrid molecular simulations of free energy geometry optimization succeeded in reproducing the experimentally observed wide spectral shifts, and revealed that protein flexibility, through which the active site structure of the protein and bound water molecules is altered by remote mutations, plays a significant role in inducing the large spectral shifts.

The Impact of the Polymer Chain Length on the Catalytic Activity of Poly(N-vinyl-2-pyrrolidone)-supported Gold Nanoclusters.

PubMed

Haesuwannakij, Setsiri; Kimura, Tetsunari; Furutani, Yuji; Okumura, Kazu; Kokubo, Ken; Sakata, Takao; Yasuda, Hidehiro; Yakiyama, Yumi; Sakurai, Hidehiro

2017-08-29

Poly(N-vinyl-2-pyrrolidone) (PVP) of varying molecular weight (M w  = 40-360 kDa) were employed to stabilize gold nanoclusters of varying size. The resulting Au:PVP clusters were subsequently used as catalysts for a kinetic study on the sized-dependent aerobic oxidation of 1-indanol, which was monitored by time-resolved in situ infrared spectroscopy. The obtained results suggest that the catalytic behaviour is intimately correlated to the size of the clusters, which in turn depends on the molecular weight of the PVPs. The highest catalytic activity was observed for clusters with a core size of ~7 nm, and the size of the cluster should increase with the molecular weight of the polymer in order to maintain optimal catalytic activity. Studies on the electronic and colloid structure of these clusters revealed that the negative charge density on the cluster surface also strongly depends on the molecular weight of the stabilizing polymers.

Motional timescale predictions by molecular dynamics simulations: Case study using proline and hydroxyproline sidechain dynamics

PubMed Central

Aliev, Abil E; Kulke, Martin; Khaneja, Harmeet S; Chudasama, Vijay; Sheppard, Tom D; Lanigan, Rachel M

2014-01-01

We propose a new approach for force field optimizations which aims at reproducing dynamics characteristics using biomolecular MD simulations, in addition to improved prediction of motionally averaged structural properties available from experiment. As the source of experimental data for dynamics fittings, we use 13C NMR spin-lattice relaxation times T1 of backbone and sidechain carbons, which allow to determine correlation times of both overall molecular and intramolecular motions. For structural fittings, we use motionally averaged experimental values of NMR J couplings. The proline residue and its derivative 4-hydroxyproline with relatively simple cyclic structure and sidechain dynamics were chosen for the assessment of the new approach in this work. Initially, grid search and simplexed MD simulations identified large number of parameter sets which fit equally well experimental J couplings. Using the Arrhenius-type relationship between the force constant and the correlation time, the available MD data for a series of parameter sets were analyzed to predict the value of the force constant that best reproduces experimental timescale of the sidechain dynamics. Verification of the new force-field (termed as AMBER99SB-ILDNP) against NMR J couplings and correlation times showed consistent and significant improvements compared to the original force field in reproducing both structural and dynamics properties. The results suggest that matching experimental timescales of motions together with motionally averaged characteristics is the valid approach for force field parameter optimization. Such a comprehensive approach is not restricted to cyclic residues and can be extended to other amino acid residues, as well as to the backbone. Proteins 2014; 82:195–215. © 2013 Wiley Periodicals, Inc. PMID:23818175

Discrete Optimization of Electronic Hyperpolarizabilities in a Chemical Subspace

DTIC Science & Technology

2009-05-01

molecular design. Methods for optimization in discrete spaces have been studied extensively and recently reviewed ( 5). Optimization methods include...integer programming, as in branch-and-bound techniques (including dead-end elimination [ 6]), simulated annealing ( 7), and genetic algorithms ( 8...These algorithms have found renewed interest and application in molecular and materials design (9- 12) . Recently, new approaches have been

Characterization and kinetics of surface functionalization and binding of biologically and chemically significant molecules

NASA Astrophysics Data System (ADS)

Steiner, Rachel

The purpose of this project is to investigate intermolecular interactions of organic molecular assemblies. By understanding the structure and physical interactions in these assemblies, we gain insights into practical applications for nanoscale systems built upon these surface structures. It is possible for organic chemists to create many forms of modified organic molecules, functionalizing them with specific reactive end groups. Through surface functionalization, enabling covalent or highly associative binding, it is possible to create ordered molecular assemblies of these molecules. Scientists can study the nature of this structure and the intermolecular interactions through spectroscopic, optical, and scattering experiments. To understand the self-assembly process in molecular systems, we preliminarily created monolayer films on silica substrates with a variety of organic molecules. In particular, we functionalized silica substrates with hydroxyl groups and covalently bound acid chloride functionalized aromatic compounds, with and without an underlying adhesion layer of 3-aminopropyltriethoxysilane. We characterized the monolayer assemblies with ellipsometry, UV-vis absorption spectroscopy, FTIR spectroscopy, and fluorescence/photoemission spectroscopy, obtaining a quantitative measure of the molecular surface coverage. In order to understand the nature of these molecular assemblies, we also pursued an in-depth kinetic study to control and optimize the monolayer formation process. Through use of UV-vis spectroscopy, we determined that the monolayer formation can best be modeled with diffusion-limited Langmuir kinetics. Specifically, we concluded that for anthracene acid chloride in dichloromethane the average diffusion coefficient was 1.6x10-7 cm2/sec. Additionally, we find we are able to achieve surface coverages of approximately 2x1014 molecules/cm2. Having established the ability to create ordered molecular assemblies, through surface functionalization, enabling covalent or highly associative binding, we continued to explore the field of molecular assemblies by studying the binding and structure of molecules to carbon nanostructures. Previous studies have shown that alkyl side chains and aromatic compounds, such as pyrene, will bind non-covalently to the sidewalls of carbon nanotubes through pi-pi interactions. We explored functionalization of carbon nanotubes and graphene by using microscopy to examine the adsorption of biomolecules onto nanotube sidewalls and graphene.

Even the Odd Numbers Help: Failure Modes of SAM-Based Tunnel Junctions Probed via Odd-Even Effects Revealed in Synchrotrons and Supercomputers.

PubMed

Thompson, Damien; Nijhuis, Christian A

2016-10-18

This Account describes a body of research in atomic level design, synthesis, physicochemical characterization, and macroscopic electrical testing of molecular devices made from ferrocene-functionalized alkanethiol molecules, which are molecular diodes, with the aim to identify, and resolve, the failure modes that cause leakage currents. The mismatch in size between the ferrocene headgroup and alkane rod makes waxlike highly dynamic self-assembled monolayers (SAMs) on coinage metals that show remarkable atomic-scale sensitivity in their electrical properties. Our results make clear that molecular tunnel junction devices provide an excellent testbed to probe the electronic and supramolecular structures of SAMs on inorganic substrates. Contacting these SAMs to a eutectic "EGaIn" alloy top-electrode, we designed highly stable long-lived molecular switches of the form electrode-SAM-electrode with robust rectification ratios of up to 3 orders of magnitude. The graphic that accompanies this conspectus displays a computed SAM packing structure, illustrating the lollipop shape of the molecules that gives dynamic SAM supramolecular structures and also the molecule-electrode van der Waals (vdW) contacts that must be controlled to form good SAM-based devices. In this Account, we first trace the evolution of SAM-based electronic devices and rationalize their operation using energy level diagrams. We describe the measurement of device properties using near edge X-ray absorption fine structure spectroscopy, cyclic voltammetry, and X-ray photoelectron spectroscopy complemented by molecular dynamics and electronic structure calculations together with large numbers of electrical measurements. We discuss how data obtained from these combined experimental/simulation codesign studies demonstrate control over the supramolecular and electronic structure of the devices, tuning odd-even effects to optimize inherent packing tendencies of the molecules in order to minimize leakage currents in the junctions. It is now possible, but still very costly to create atomically smooth electrodes and we discuss progress toward masking electrode imperfections using cooperative molecule-electrode contacts that are only accessible by dynamic SAM structures. Finally, the unique ability of SAM devices to achieve simultaneously high and atom-sensitive electrical switching is summarized and discussed. While putting these structures to work as real world electronic devices remains very challenging, we speculate on the scientific and technological advances that are required to further improve electronic and supramolecular structure, toward the creation of high yields of long-lived molecular devices with (very) large, reproducible rectification ratios.

Could LogP be a principal determinant of biological activity in 18-crown-6 ethers? Synthesis of biologically active adamantane-substituted diaza-crowns.

PubMed

Supek, Fran; Ramljak, Tatjana Šumanovac; Marjanović, Marko; Buljubašić, Maja; Kragol, Goran; Ilić, Nataša; Smuc, Tomislav; Zahradka, Davor; Mlinarić-Majerski, Kata; Kralj, Marijeta

2011-08-01

18-crown-6 ethers are known to exert their biological activity by transporting K(+) ions across cell membranes. Using non-linear Support Vector Machines regression, we searched for structural features that influence antiproliferative activity in a diverse set of 19 known oxa-, monoaza- and diaza-18-crown-6 ethers. Here, we show that the logP of the molecule is the most important molecular descriptor, among ∼1300 tested descriptors, in determining biological potency (R(2)(cv) = 0.704). The optimal logP was at 5.5 (Ghose-Crippen ALOGP estimate) while both higher and lower values were detrimental to biological potency. After controlling for logP, we found that the antiproliferative activity of the molecule was generally not affected by side chain length, molecular symmetry, or presence of side chain amide links. To validate this QSAR model, we synthesized six novel, highly lipophilic diaza-18-crown-6 derivatives with adamantane moieties attached to the side arms. These compounds have near-optimal logP values and consequently exhibit strong growth inhibition in various human cancer cell lines and a bacterial system. The bioactivities of different diaza-18-crown-6 analogs in Bacillus subtilis and cancer cells were correlated, suggesting conserved molecular features may be mediating the cytotoxic response. We conclude that relying primarily on the logP is a sensible strategy in preparing future 18-crown-6 analogs with optimized biological activity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Optimization of constrained density functional theory

NASA Astrophysics Data System (ADS)

O'Regan, David D.; Teobaldi, Gilberto

2016-07-01

Constrained density functional theory (cDFT) is a versatile electronic structure method that enables ground-state calculations to be performed subject to physical constraints. It thereby broadens their applicability and utility. Automated Lagrange multiplier optimization is necessary for multiple constraints to be applied efficiently in cDFT, for it to be used in tandem with geometry optimization, or with molecular dynamics. In order to facilitate this, we comprehensively develop the connection between cDFT energy derivatives and response functions, providing a rigorous assessment of the uniqueness and character of cDFT stationary points while accounting for electronic interactions and screening. In particular, we provide a nonperturbative proof that stable stationary points of linear density constraints occur only at energy maxima with respect to their Lagrange multipliers. We show that multiple solutions, hysteresis, and energy discontinuities may occur in cDFT. Expressions are derived, in terms of convenient by-products of cDFT optimization, for quantities such as the dielectric function and a condition number quantifying ill definition in multiple constraint cDFT.

Prediction of chemical biodegradability using support vector classifier optimized with differential evolution.

PubMed

Cao, Qi; Leung, K M

2014-09-22

Reliable computer models for the prediction of chemical biodegradability from molecular descriptors and fingerprints are very important for making health and environmental decisions. Coupling of the differential evolution (DE) algorithm with the support vector classifier (SVC) in order to optimize the main parameters of the classifier resulted in an improved classifier called the DE-SVC, which is introduced in this paper for use in chemical biodegradability studies. The DE-SVC was applied to predict the biodegradation of chemicals on the basis of extensive sample data sets and known structural features of molecules. Our optimization experiments showed that DE can efficiently find the proper parameters of the SVC. The resulting classifier possesses strong robustness and reliability compared with grid search, genetic algorithm, and particle swarm optimization methods. The classification experiments conducted here showed that the DE-SVC exhibits better classification performance than models previously used for such studies. It is a more effective and efficient prediction model for chemical biodegradability.

Binding free energy analysis of protein-protein docking model structures by evERdock.

PubMed

Takemura, Kazuhiro; Matubayasi, Nobuyuki; Kitao, Akio

2018-03-14

To aid the evaluation of protein-protein complex model structures generated by protein docking prediction (decoys), we previously developed a method to calculate the binding free energies for complexes. The method combines a short (2 ns) all-atom molecular dynamics simulation with explicit solvent and solution theory in the energy representation (ER). We showed that this method successfully selected structures similar to the native complex structure (near-native decoys) as the lowest binding free energy structures. In our current work, we applied this method (evERdock) to 100 or 300 model structures of four protein-protein complexes. The crystal structures and the near-native decoys showed the lowest binding free energy of all the examined structures, indicating that evERdock can successfully evaluate decoys. Several decoys that show low interface root-mean-square distance but relatively high binding free energy were also identified. Analysis of the fraction of native contacts, hydrogen bonds, and salt bridges at the protein-protein interface indicated that these decoys were insufficiently optimized at the interface. After optimizing the interactions around the interface by including interfacial water molecules, the binding free energies of these decoys were improved. We also investigated the effect of solute entropy on binding free energy and found that consideration of the entropy term does not necessarily improve the evaluations of decoys using the normal model analysis for entropy calculation.

Binding free energy analysis of protein-protein docking model structures by evERdock

NASA Astrophysics Data System (ADS)

Takemura, Kazuhiro; Matubayasi, Nobuyuki; Kitao, Akio

2018-03-01

To aid the evaluation of protein-protein complex model structures generated by protein docking prediction (decoys), we previously developed a method to calculate the binding free energies for complexes. The method combines a short (2 ns) all-atom molecular dynamics simulation with explicit solvent and solution theory in the energy representation (ER). We showed that this method successfully selected structures similar to the native complex structure (near-native decoys) as the lowest binding free energy structures. In our current work, we applied this method (evERdock) to 100 or 300 model structures of four protein-protein complexes. The crystal structures and the near-native decoys showed the lowest binding free energy of all the examined structures, indicating that evERdock can successfully evaluate decoys. Several decoys that show low interface root-mean-square distance but relatively high binding free energy were also identified. Analysis of the fraction of native contacts, hydrogen bonds, and salt bridges at the protein-protein interface indicated that these decoys were insufficiently optimized at the interface. After optimizing the interactions around the interface by including interfacial water molecules, the binding free energies of these decoys were improved. We also investigated the effect of solute entropy on binding free energy and found that consideration of the entropy term does not necessarily improve the evaluations of decoys using the normal model analysis for entropy calculation.

Facile synthesis, single crystal analysis, and computational studies of sulfanilamide derivatives

NASA Astrophysics Data System (ADS)

Tahir, Muhammad Nawaz; Khalid, Muhammad; Islam, Ayesha; Ali Mashhadi, Syed Muddassir; Braga, Ataualpa A. C.

2017-01-01

Antibacterial resistance is a worldwide problem. Sulfanilamide is widely used antibacterial. For the first time, we report here a simple method for the derivative synthesis of the title drugs, single crystal XRD and density functional theory (DFT) studies. The optimized molecular structure, natural bond orbital (NBO), frontier molecular orbitals (FMOs) molecular electrostatic potential studies (MEP) and Mulliken population analysis (MPA) have been performed using M06-2X/6-31G(d, p). The FT-IR spectra and thermodynamic parameters were calculated at M06-2X/6-311 + G(2d,p) and B3LYP/6-31G(d, p) levels respectively, while, the UV-Vis analysis was performed using TD-DFT/B3LYP/6-31G(d, p) method. The experimental FT-IR spectra of both compounds were also carried out to reconfirm sbnd H⋯Osbnd hydrogen bonds. The DFT optimized parameters exhibiting good agreement with the experimental data. NBO analysis explored the hyper conjugative interaction and stability of title crystals, especially, reconfirmed the existence of sbnd H⋯Osbnd hydrogen bonds between the dimers. The FT-IR, thermodynamic parameters, MEP and MPA also revealed the hydrogen bonding detail is harmonious to XRD data. As a matter of the fact, the hydrogen bonding is a significant parameter for the understanding and design of molecular crystals, subsequently; it can also play a vital role in the supramolecular chemistry. Moreover, the global reactivity descriptors suggest that title compounds might be bioactive.

Tunneling Nanoelectromechanical Switches Based on Compressible Molecular Thin Films.

PubMed

Niroui, Farnaz; Wang, Annie I; Sletten, Ellen M; Song, Yi; Kong, Jing; Yablonovitch, Eli; Swager, Timothy M; Lang, Jeffrey H; Bulović, Vladimir

2015-08-25

Abrupt switching behavior and near-zero leakage current of nanoelectromechanical (NEM) switches are advantageous properties through which NEMs can outperform conventional semiconductor electrical switches. To date, however, typical NEMs structures require high actuation voltages and can prematurely fail through permanent adhesion (defined as stiction) of device components. To overcome these challenges, in the present work we propose a NEM switch, termed a "squitch," which is designed to electromechanically modulate the tunneling current through a nanometer-scale gap defined by an organic molecular film sandwiched between two electrodes. When voltage is applied across the electrodes, the generated electrostatic force compresses the sandwiched molecular layer, thereby reducing the tunneling gap and causing an exponential increase in the current through the device. The presence of the molecular layer avoids direct contact of the electrodes during the switching process. Furthermore, as the layer is compressed, the increasing surface adhesion forces are balanced by the elastic restoring force of the deformed molecules which can promote zero net stiction and recoverable switching. Through numerical analysis, we demonstrate the potential of optimizing squitch design to enable large on-off ratios beyond 6 orders of magnitude with operation in the sub-1 V regime and with nanoseconds switching times. Our preliminary experimental results based on metal-molecule-graphene devices suggest the feasibility of the proposed tunneling switching mechanism. With optimization of device design and material engineering, squitches can give rise to a broad range of low-power electronic applications.

Orbital-Optimized MP3 and MP2.5 with Density-Fitting and Cholesky Decomposition Approximations.

PubMed

Bozkaya, Uğur

2016-03-08

Efficient implementations of the orbital-optimized MP3 and MP2.5 methods with the density-fitting (DF-OMP3 and DF-OMP2.5) and Cholesky decomposition (CD-OMP3 and CD-OMP2.5) approaches are presented. The DF/CD-OMP3 and DF/CD-OMP2.5 methods are applied to a set of alkanes to compare the computational cost with the conventional orbital-optimized MP3 (OMP3) [Bozkaya J. Chem. Phys. 2011, 135, 224103] and the orbital-optimized MP2.5 (OMP2.5) [Bozkaya and Sherrill J. Chem. Phys. 2014, 141, 204105]. Our results demonstrate that the DF-OMP3 and DF-OMP2.5 methods provide considerably lower computational costs than OMP3 and OMP2.5. Further application results show that the orbital-optimized methods are very helpful for the study of open-shell noncovalent interactions, aromatic bond dissociation energies, and hydrogen transfer reactions. We conclude that the DF-OMP3 and DF-OMP2.5 methods are very promising for molecular systems with challenging electronic structures.

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

Ma, Biao; Yamaguchi, Keiichi; Fukuoka, Mayuko

To accelerate the logical drug design procedure, we created the program “NAGARA,” a plugin for PyMOL, and applied it to the discovery of small compounds called medical chaperones (MCs) that stabilize the cellular form of a prion protein (PrP{sup C}). In NAGARA, we constructed a single platform to unify the docking simulation (DS), free energy calculation by molecular dynamics (MD) simulation, and interfragment interaction energy (IFIE) calculation by quantum chemistry (QC) calculation. NAGARA also enables large-scale parallel computing via a convenient graphical user interface. Here, we demonstrated its performance and its broad applicability from drug discovery to lead optimization withmore » full compatibility with various experimental methods including Western blotting (WB) analysis, surface plasmon resonance (SPR), and nuclear magnetic resonance (NMR) measurements. Combining DS and WB, we discovered anti-prion activities for two compounds and tegobuvir (TGV), a non-nucleoside non-structural protein NS5B polymerase inhibitor showing activity against hepatitis C virus genotype 1. Binding profiles predicted by MD and QC are consistent with those obtained by SPR and NMR. Free energy analyses showed that these compounds stabilize the PrP{sup C} conformation by decreasing the conformational fluctuation of the PrP{sup C}. Because TGV has been already approved as a medicine, its extension to prion diseases is straightforward. Finally, we evaluated the affinities of the fragmented regions of TGV using QC and found a clue for its further optimization. By repeating WB, MD, and QC recursively, we were able to obtain the optimum lead structure. - Highlights: • NAGARA integrates docking simulation, molecular dynamics, and quantum chemistry. • We found many compounds, e.g., tegobuvir (TGV), that exhibit anti-prion activities. • We obtained insights into the action mechanism of TGV as a medical chaperone. • Using QC, we obtained useful information for optimization of the lead compound, TGV. • NAGARA is a convenient platform for drug discovery and lead optimization.« less

Computational and spectroscopic studies of a new Schiff base 3-hydroxy-4-methoxybenzylidene(2-hydroxyphenyl)amine and molecular structure of its corresponding zwitterionic form.

PubMed

Habibi, Mohammad Hossein; Shojaee, Elahe; Ranjbar, Mahnaz; Memarian, Hamid Reza; Kanayama, Akihiko; Suzuki, Takayoshi

2013-03-15

Computational and spectroscopic properties of a novel Schiff base compound, 3-hydroxy-4-methoxybenzylidene(2-hydroxyphenyl)amine were studied. The crystal structures of the title compound and its corresponding zwitterionic form were analyzed by X-ray diffraction. The presence of N-H, C-O and C=N stretching vibrations in IR spectrum strongly suggest that the title compound has zwitterionic form in the solid state. Molecular geometry of the title compound in the ground state has been calculated using the density functional method (DFT) at B3LYP 6-31++G(d,p) basis set and was compared with the experimental data. The calculated results of the title compound show that the optimized geometry can well reproduce the crystal structure. The molecule shows absorption bands at 345 and 363 nm in EtOH. The shoulder-shaped bands at 415 nm can be assigned to n→π(*) transitions. The absorption band is observed at 285 nm in EtOH corresponds to the π→π(*) transitions. Copyright © 2012 Elsevier B.V. All rights reserved.

Trapped in imidazole: how to accumulate multiple photoelectrons on a black-absorbing ruthenium complex.

PubMed

Zedler, Linda; Kupfer, Stephan; de Moraes, Inês Rabelo; Wächtler, Maria; Beckert, Rainer; Schmitt, Michael; Popp, Jürgen; Rau, Sven; Dietzek, Benjamin

2014-03-24

Ruthenium dyes incorporating a 4H-imidazole chromophore as a ligand exhibit a spectrally broad absorption in the UV/Vis region. Furthermore, they show the ability to store two electrons within the 4H-imidazole ligand. These features render them promising molecular systems, for example, as inter- or intramolecular electron relays. To optimize the structures with respect to their electron-storage capability, it is crucial to understand the impact of structural changes accompanying photoinduced charge transfer in the electronic intermediates of multistep electron-transfer processes. The photophysical properties of these (reactive) intermediates might impact the function of the molecular systems quite substantially. However, the spectroscopic study of short-lived intermediates in stepwise multielectron-transfer processes is experimentally challenging. To this end, this contribution reports on the electrochemical generation of anions identical to intermediate structures and their spectroscopic characterization by in situ resonance Raman and UV/Vis spectroelectrochemistry and computational methods. Thereby, an efficient two-electron pathway to the 4H-imidazole electron-accepting ligand is identified. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimizing legacy molecular dynamics software with directive-based offload

NASA Astrophysics Data System (ADS)

Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

2015-10-01

Directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In this paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also result in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMPS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel® Xeon Phi™ coprocessors and NVIDIA GPUs. The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS.

Use of the Monte Carlo Method for OECD Principles-Guided QSAR Modeling of SIRT1 Inhibitors.

PubMed

Kumar, Ashwani; Chauhan, Shilpi

2017-01-01

SIRT1 inhibitors offer therapeutic potential for the treatment of a number of diseases including cancer and human immunodeficiency virus infection. A diverse series of 45 compounds with reported SIRT1 inhibitory activity has been employed for the development of quantitative structure-activity relationship (QSAR) models using the Monte Carlo optimization method. This method makes use of simplified molecular input line entry system notation of the molecular structure. The QSAR models were built up according to OECD principles. Three subsets of three splits were examined and validated by respective external sets. All the three described models have good statistical quality. The best model has the following statistical characteristics: R 2  = 0.8350, Q 2 test  = 0.7491 for the test set and R 2  = 0.9655, Q 2 ext  = 0.9261 for the validation set. In the mechanistic interpretation, structural attributes responsible for the endpoint increase and decrease are defined. Further, the design of some prospective SIRT1 inhibitors is also presented on the basis of these structural attributes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular structure, Hirshfeld surface analysis, theoretical investigations and nonlinear optical properties of a novel crystalline chalcone derivative: (E)-1-(5-bromothiophen-2-yl)-3-(p-tolyl)prop-2-en-1-one

NASA Astrophysics Data System (ADS)

Pramodh, B.; Lokanath, N. K.; Naveen, S.; Naresh, P.; Ganguly, S.; Panda, J.

2018-06-01

In the present work, the crystal structure of a novel chalcone derivative, (E)-1-(5-bromothiophen-2-yl)-3-(p-tolyl) prop-2-en-1-one has been confirmed by X-ray diffraction studies. Hirshfeld surface analysis was carried out to explore the intermolecular interactions. From the Hirshfeld surface analysis it was observed that H⋯H (26.7%) and C⋯H (26.3%) are the major contributors to the intermolecular interactions which stabilizes the crystal structure. The coordinates were optimized using the density functional theory (DFT) calculations using B3LYP hybrid functions with 6-31G(d) basis set. The structural parameters obtained from XRD studies compliment with those calculated using DFT calculations. The HOMO and LUMO energy gap was found to be 4.1778 eV. The molecular electrostatic potential (MEP) was plotted to identify the possible reactions sites of the molecule. Further, non-linear optical (NLO) properties were investigated by calculating hyperpolarizabilities which indicate that the title compound would be a potential candidate for the NLO applications.

Crystal structure, spectral property, antimicrobial activity and DFT calculation of N-(coumarin-3-yl)-N‧-(2-amino-5-phenyl-1,3,4-thiadiazol-2-yl) urea

NASA Astrophysics Data System (ADS)

Zhang, Hong-Song; Zhang, Kong-Yan; Chen, Li-Chuan; Li, Yao-Xin; Chai, Lan-Qin

2017-10-01

N-(coumarin-3-yl)-N‧-(2-amino-5-phenyl-1,3,4-thiadiazol-2-yl) urea was synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR, UV-Vis and emission spectroscopy, as well as by single-crystal X-ray diffraction. X-ray crystallographic analyses have indicated that the crystal structure consists of two dimethyl sulfoxide (DMSO) solvent molecules and the structural geometry of DMSO is a trigonal pyramid in shape. In the crystal structure, a self-assembling two-dimensional (2-D) layer supramolecular architecture is formed through intermolecular hydrogen bonds, Cdbnd O···π (thiadiazole ring) and π···π stacking interactions. The geometry of the compound has been optimized by the DFT method and the results are compared with the X-ray diffraction data. The electronic transitions and spectral features of the compound were carried out by using DFT/B3LYP method. In addition, the antimicrobial activity was also studied, and the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and HOMO-LUMO gap were also calculated.

Low energy isomers of (H2O)25 from a hierarchical method based on Monte Carlo Temperature Basin Paving and Molecular Tailoring Approaches benchmarked by full MP2 calculations

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

Sahu, Nityananda; Gadre, Shridhar R.; Bandyopadhyay, Pradipta

We report new global minimum candidate structures for the (H2O)25 cluster that are lower in energy than the ones reported previously and correspond to hydrogen bonded networks with 42 hydrogen bonds and an interior, fully coordinated water molecule. These were obtained as a result of a hierarchical approach based on initial Monte Carlo Temperature Basin Paving (MCTBP) sampling of the cluster’s Potential Energy Surface (PES) with the Effective Fragment Potential (EFP), subsequent geometry optimization using the Molecular Tailoring fragmentation Approach (MTA) and final refinement at the second order Møller Plesset perturbation (MP2) level of theory. The MTA geometry optimizations usedmore » between 14 and 18 main fragments with maximum sizes between 11 and 14 water molecules and average size of 10 water molecules, whose energies and gradients were computed at the MP2 level. The MTA-MP2 optimized geometries were found to be quite close (within < 0.5 kcal/mol) to the ones obtained from the MP2 optimization of the whole cluster. The grafting of the MTA-MP2 energies yields electronic energies that are within < 5×10-4 a.u. from the MP2 results for the whole cluster while preserving their energy order. The MTA-MP2 method was also found to reproduce the MP2 harmonic vibrational frequencies in both the HOH bending and the OH stretching regions.« less

Optimal Ge/SiGe nanofin geometries for hole mobility enhancement: Technology limit from atomic simulations

NASA Astrophysics Data System (ADS)

Vedula, Ravi Pramod; Mehrotra, Saumitra; Kubis, Tillmann; Povolotskyi, Michael; Klimeck, Gerhard; Strachan, Alejandro

2015-05-01

We use first principles simulations to engineer Ge nanofins for maximum hole mobility by controlling strain tri-axially through nano-patterning. Large-scale molecular dynamics predict fully relaxed, atomic structures for experimentally achievable nanofins, and orthogonal tight binding is used to obtain the corresponding electronic structure. Hole transport properties are then obtained via a linearized Boltzmann formalism. This approach explicitly accounts for free surfaces and associated strain relaxation as well as strain gradients which are critical for quantitative predictions in nanoscale structures. We show that the transverse strain relaxation resulting from the reduction in the aspect ratio of the fins leads to a significant enhancement in phonon limited hole mobility (7× over unstrained, bulk Ge, and 3.5× over biaxially strained Ge). Maximum enhancement is achieved by reducing the width to be approximately 1.5 times the height and further reduction in width does not result in additional gains. These results indicate significant room for improvement over current-generation Ge nanofins, provide geometrical guidelines to design optimized geometries and insight into the physics behind the significant mobility enhancement.

Optimized Assembly of a Multifunctional RNA-Protein Nanostructure in a Cell-Free Gene Expression System.

PubMed

Schwarz-Schilling, Matthaeus; Dupin, Aurore; Chizzolini, Fabio; Krishnan, Swati; Mansy, Sheref S; Simmel, Friedrich C

2018-04-11

Molecular complexes composed of RNA molecules and proteins are promising multifunctional nanostructures for a wide variety of applications in biological cells or in artificial cellular systems. In this study, we systematically address some of the challenges associated with the expression and assembly of such hybrid structures using cell-free gene expression systems. As a model structure, we investigated a pRNA-derived RNA scaffold functionalized with four distinct aptamers, three of which bind to proteins, streptavidin and two fluorescent proteins, while one binds the small molecule dye malachite green (MG). Using MG fluorescence and Förster resonance energy transfer (FRET) between the RNA-scaffolded proteins, we assess critical assembly parameters such as chemical stability, binding efficiency, and also resource sharing effects within the reaction compartment. We then optimize simultaneous expression and coassembly of the RNA-protein nanostructure within a single-compartment cell-free gene expression system. We demonstrate expression and assembly of the multicomponent nanostructures inside of emulsion droplets and their aptamer-mediated localization onto streptavidin-coated substrates, plus the successful assembly of the hybrid structures inside of bacterial cells.

Biosorption of six basic and acidic dyes on brown alga Sargassum ilicifolium: optimization, kinetic and isotherm studies.

PubMed

Tabaraki, Reza; Sadeghinejad, Negar

2017-06-01

Biosorption of Methyl Blue (MB), Fuchsin Acid (FA), Rhodamine B (RB), Methylene Blue (MEB), Bromocresol purple (BC) and Methyl Orange (MO) onto Sargassum ilicifolium was studied in a batch system. Effect of dye structure on biosorption by Sargassum ilicifolium was studied to define the correlation between chemical structure and biosorption capacity. Different dye groups such as triarylmethane (MB, FA and BC), monoazo (MO), thiazine (MEB) and xanthene (RB) were studied. At optimum experimental conditions for each dye, biosorption capacity was determined and compared. The results indicate that the chemical structure (triarylmethane, monoazo, thiazine, xanthene), number of sulfonic groups, basicity (element of chromophore group: S, N, O) and molecular weight of dye molecules influence their biosorption capacity. Experimental parameters such as biosorbent dose, pH, contact time, and initial dye concentration were optimized for each dye. The biosorption kinetic data were successfully described by the pseudo second-order model. The biosorption results were also analyzed by the Langmuir and Freundlich isotherms. Finally, biosorption capacities obtained using Sargassum ilicifolium were compared with the ones presented in the literature.

Vibrational spectra, DFT quantum chemical calculations and conformational analysis of P-iodoanisole.

PubMed

Arivazhagan, M; Anitha Rexalin, D; Geethapriya, J

2013-09-01

The solid phase FT-IR and FT-Raman spectra of P-iodoanisole (P-IA) have been recorded in the regions 400-4000 and 50-4000 cm(-1), respectively. The spectra were interpreted in terms of fundamentals modes, combination and overtone bands. The structure of the molecule was optimized and the structural characteristics were determined by ab initio (HF) and density functional theory (B3LYP) methods with LanL2DZ as basis set. The potential energy surface scan for the selected dihedral angle of P-IA has been performed to identify stable conformer. The optimized structure parameters and vibrational wavenumbers of stable conformer have been predicted by density functional B3LYP method with LanL2DZ (with effective core potential representations of electrons near the nuclei for post-third row atoms) basis set. The nucleophilic and electrophilic sites obtained from the molecular electrostatic potential (MEP) surface were calculated. The temperature dependence of thermodynamic properties has been analyzed. Several thermodynamic parameters have been calculated using B3LYP with LanL2DZ basis set. Copyright © 2013 Elsevier B.V. All rights reserved.

Structure and electronic absorption spectra of nematogenic alkoxycinnamic acids - a comparative study based on semiempirical and DFT methods.

PubMed

Praveen, Pogula Lakshmi; Ojha, Durga Prasad

2012-04-01

Structure of nematogenic p-n-Alkoxy cinnamic acids (nOCAC) with various alkyl chain carbon atoms (n = 2, 4, 6, 8) has been optimized using density functional B3LYP with 6-31+G (d) basis set using crystallographic geometry as input. Using the optimized geometry, electronic structure of the molecules has been evaluated using the semiempirical methods and DFT calculations. Molecular charge distribution and phase stability of these systems have been analyzed based on Mulliken and Löwdin population analysis. The electronic absorption spectra of nOCAC molecules have been simulated by employing DFT method, semiempirical CNDO/S and INDO/S parameterizations. Two types of calculations have been performed for model systems containing single and double molecules of nOCAC. UV-Visible spectra have been calculated for all single molecules. The UV stability of the molecules has been discussed in light of the electronic transition oscillator strength (f). The dimer complexes of higher homologues (n = 6, 8) have also been reported to enable the comparison between single and double molecules.

Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models.

PubMed

Qin, Zhao; Buehler, Markus J

2011-01-01

Intermediate filaments, in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, and play an important role in mechanotransduction as well as in providing mechanical stability to cells at large stretch. The molecular structures, mechanical and dynamical properties of the intermediate filament basic building blocks, the dimer and the tetramer, however, have remained elusive due to persistent experimental challenges owing to the large size and fibrillar geometry of this protein. We have recently reported an atomistic-level model of the human vimentin dimer and tetramer, obtained through a bottom-up approach based on structural optimization via molecular simulation based on an implicit solvent model (Qin et al. in PLoS ONE 2009 4(10):e7294, 9). Here we present extensive simulations and structural analyses of the model based on ultra large-scale atomistic-level simulations in an explicit solvent model, with system sizes exceeding 500,000 atoms and simulations carried out at 20 ns time-scales. We report a detailed comparison of the structural and dynamical behavior of this large biomolecular model with implicit and explicit solvent models. Our simulations confirm the stability of the molecular model and provide insight into the dynamical properties of the dimer and tetramer. Specifically, our simulations reveal a heterogeneous distribution of the bending stiffness along the molecular axis with the formation of rather soft and highly flexible hinge-like regions defined by non-alpha-helical linker domains. We report a comparison of Ramachandran maps and the solvent accessible surface area between implicit and explicit solvent models, and compute the persistence length of the dimer and tetramer structure of vimentin intermediate filaments for various subdomains of the protein. Our simulations provide detailed insight into the dynamical properties of the vimentin dimer and tetramer intermediate filament building blocks, which may guide the development of novel coarse-grained models of intermediate filaments, and could also help in understanding assembly mechanisms.

Thermostability of In Vitro Evolved Bacillus subtilis Lipase A: A Network and Dynamics Perspective

PubMed Central

Srivastava, Ashutosh; Sinha, Somdatta

2014-01-01

Proteins in thermophilic organisms remain stable and function optimally at high temperatures. Owing to their important applicability in many industrial processes, such thermostable proteins have been studied extensively, and several structural factors attributed to their enhanced stability. How these factors render the emergent property of thermostability to proteins, even in situations where no significant changes occur in their three-dimensional structures in comparison to their mesophilic counter-parts, has remained an intriguing question. In this study we treat Lipase A from Bacillus subtilis and its six thermostable mutants in a unified manner and address the problem with a combined complex network-based analysis and molecular dynamic studies to find commonality in their properties. The Protein Contact Networks (PCN) of the wild-type and six mutant Lipase A structures developed at a mesoscopic scale were analyzed at global network and local node (residue) level using network parameters and community structure analysis. The comparative PCN analysis of all proteins pointed towards important role of specific residues in the enhanced thermostability. Network analysis results were corroborated with finer-scale molecular dynamics simulations at both room and high temperatures. Our results show that this combined approach at two scales can uncover small but important changes in the local conformations that add up to stabilize the protein structure in thermostable mutants, even when overall conformation differences among them are negligible. Our analysis not only supports the experimentally determined stabilizing factors, but also unveils the important role of contacts, distributed throughout the protein, that lead to thermostability. We propose that this combined mesoscopic-network and fine-grained molecular dynamics approach is a convenient and useful scheme not only to study allosteric changes leading to protein stability in the face of negligible over-all conformational changes due to mutations, but also in other molecular networks where change in function does not accompany significant change in the network structure. PMID:25122499

An optimal strategy for functional mapping of dynamic trait loci.

PubMed

Jin, Tianbo; Li, Jiahan; Guo, Ying; Zhou, Xiaojing; Yang, Runqing; Wu, Rongling

2010-02-01

As an emerging powerful approach for mapping quantitative trait loci (QTLs) responsible for dynamic traits, functional mapping models the time-dependent mean vector with biologically meaningful equations and are likely to generate biologically relevant and interpretable results. Given the autocorrelation nature of a dynamic trait, functional mapping needs the implementation of the models for the structure of the covariance matrix. In this article, we have provided a comprehensive set of approaches for modelling the covariance structure and incorporated each of these approaches into the framework of functional mapping. The Bayesian information criterion (BIC) values are used as a model selection criterion to choose the optimal combination of the submodels for the mean vector and covariance structure. In an example for leaf age growth from a rice molecular genetic project, the best submodel combination was found between the Gaussian model for the correlation structure, power equation of order 1 for the variance and the power curve for the mean vector. Under this combination, several significant QTLs for leaf age growth trajectories were detected on different chromosomes. Our model can be well used to study the genetic architecture of dynamic traits of agricultural values.

Ab-initio study on the absorption spectrum of color change sapphire based on first-principles calculations with considering lattice relaxation-effect

NASA Astrophysics Data System (ADS)

Novita, Mega; Nagoshi, Hikari; Sudo, Akiho; Ogasawara, Kazuyoshi

2018-01-01

In this study, we performed an investigation on α-Al2O3: V3+ material, or the so-called color change sapphire, based on first-principles calculations without referring to any experimental parameter. The molecular orbital (MO) structure was estimated by the one-electron MO calculations using the discrete variational-Xα (DV-Xα) method. Next, the absorption spectra were estimated by the many-electron calculations using the discrete variational multi-electron (DVME) method. The effect of lattice relaxation on the crystal structures was estimated based on the first-principles band structure calculations. We performed geometry optimizations on the pure α-Al2O3 and with the impurity V3+ ion using Cambridge Serial Total Energy Package (CASTEP) code. The effect of energy corrections such as configuration dependence correction and correlation correction was also investigated in detail. The results revealed that the structural change on the α-Al2O3: V3+ resulted from the geometry optimization improved the calculated absorption spectra. By a combination of both the lattice relaxation-effect and the energy correction-effect improve the agreement to the experiment fact.

Effect of iron content on the catalytic activity of Fe-MnOx electrodeposited films in water oxidation

NASA Astrophysics Data System (ADS)

Selinger, Elizabeth; Ryczko, Kevin; Lopinski, Gregory; Armandi, Marco; Bonelli, Barbara; Tamblyn, Isaac

We report on the experimental and computational optimization and characterization of an MnOx structure containing a small amount of Fe, used as a catalyst for the water oxidation reaction (WOR), the key limiting reaction in water splitting. MnOx materials are earth-abundant and known to be efficient for WOR, and the method of cathodically electrodepositing catalysts allows for quick synthesis and a homogeneous coverage of the substrate. We present an increase in WOR activity due to the presence of Fe in this MnOx catalyst structure. First, we explored the optimal range for Fe(NO3)3 concentration in an KMnO4 solution for electrodeposition and tested for WOR activity. The catalyst structure was then analyzed using FESEM, XPS, and a Kelvin probe. We then developed a computational model of this structure, using density functional theory to obtain adsorption energies, work functions, projected density of states, and Born-Oppenheimer molecular dynamics. In this theoretical framework, we explore how these observables change with respect to concentration of Fe, and compare the theoretical model with experiment. special acknowledgement to the Italian Cultural Centre of Durham scholarship program.

RAFT Nano-constructs: surfing to biological applications.

PubMed

Boturyn, Didier; Defrancq, Eric; Dolphin, Gunnar T; Garcia, Julian; Labbe, Pierre; Renaudet, Olivier; Dumy, Pascal

2008-02-01

Biologically programmed molecular recognition provides the basis of all natural systems and supplies evolution-optimized functional materials from self-assembly of a limited number of molecular building blocks. Biomolecules such as peptides, nucleic acids and carbohydrates represent a diverse supply of structural building blocks for the chemist to design and fabricate new functional nanostructured architectures. In this context, we review here the chemistry we have developed to conjugate peptides with nucleic acids, carbohydrates, and organic molecules, as well as combinations thereof using a template-assembled approach. With this methodology, we have prepared new integrated functional systems exhibiting designed properties in the field of nanovectors, biosensors as well as controlled peptide self-assembly. Thus this molecular engineering approach allows for the rational design of systems with integrated tailor-made properties and paves the way to more elaborate applications by bottom-up design in the domain of nanobiosciences.

Molecular characterization of multivalent bioconjugates by size-exclusion chromatography with multiangle laser light scattering.

PubMed

Pollock, Jacob F; Ashton, Randolph S; Rode, Nikhil A; Schaffer, David V; Healy, Kevin E

2012-09-19

The degree of substitution and valency of bioconjugate reaction products are often poorly judged or require multiple time- and product-consuming chemical characterization methods. These aspects become critical when analyzing and optimizing the potency of costly polyvalent bioactive conjugates. In this study, size-exclusion chromatography with multiangle laser light scattering was paired with refractive index detection and ultraviolet spectroscopy (SEC-MALS-RI-UV) to characterize the reaction efficiency, degree of substitution, and valency of the products of conjugation of either peptides or proteins to a biopolymer scaffold, i.e., hyaluronic acid (HyA). Molecular characterization was more complete compared to estimates from a protein quantification assay, and exploitation of this method led to more accurate deduction of the molecular structures of polymer bioconjugates. Information obtained using this technique can improve macromolecular engineering design principles and help to better understand multivalent macromolecular interactions in biological systems.

High thermopower of mechanically stretched single-molecule junctions

PubMed Central

Tsutsui, Makusu; Morikawa, Takanori; He, Yuhui; Arima, Akihide

2015-01-01

Metal-molecule-metal junction is a promising candidate for thermoelectric applications that utilizes quantum confinement effects in the chemically defined zero-dimensional atomic structure to achieve enhanced dimensionless figure of merit ZT. A key issue in this new class of thermoelectric nanomaterials is to clarify the sensitivity of thermoelectricity on the molecular junction configurations. Here we report simultaneous measurements of the thermoelectric voltage and conductance on Au-1,4-benzenedithiol (BDT)-Au junctions mechanically-stretched in-situ at sub-nanoscale. We obtained the average single-molecule conductance and thermopower of 0.01 G0 and 15 μV/K, respectively, suggesting charge transport through the highest occupied molecular orbital. Meanwhile, we found the single-molecule thermoelectric transport properties extremely-sensitive to the BDT bridge configurations, whereby manifesting the importance to design the electrode-molecule contact motifs for optimizing the thermoelectric performance of molecular junctions. PMID:26112999

Molecular characterization of multivalent bioconjugates by size-exclusion chromatography (SEC) with multi-angle laser light scattering (MALS)

PubMed Central

Pollock, Jacob F.; Ashton, Randolph S.; Rode, Nikhil A.; Schaffer, David V.; Healy, Kevin E.

2013-01-01

The degree of substitution and valency of bioconjugate reaction products are often poorly judged or require multiple time- and product- consuming chemical characterization methods. These aspects become critical when analyzing and optimizing the potency of costly polyvalent bioactive conjugates. In this study, size-exclusion chromatography with multi-angle laser light scattering was paired with refractive index detection and ultraviolet spectroscopy (SEC-MALS-RI-UV) to characterize the reaction efficiency, degree of substitution, and valency of the products of conjugation of either peptides or proteins to a biopolymer scaffold, i.e., hyaluronic acid (HyA). Molecular characterization was more complete compared to estimates from a protein quantification assay, and exploitation of this method led to more accurate deduction of the molecular structures of polymer bioconjugates. Information obtained using this technique can improve macromolecular engineering design principles and better understand multivalent macromolecular interactions in biological systems. PMID:22794081

Porphyrins at interfaces

NASA Astrophysics Data System (ADS)

Auwärter, Willi; Écija, David; Klappenberger, Florian; Barth, Johannes V.

2015-02-01

Porphyrins and other tetrapyrrole macrocycles possess an impressive variety of functional properties that have been exploited in natural and artificial systems. Different metal centres incorporated within the tetradentate ligand are key for achieving and regulating vital processes, including reversible axial ligation of adducts, electron transfer, light-harvesting and catalytic transformations. Tailored substituents optimize their performance, dictating their arrangement in specific environments and mediating the assembly of molecular nanoarchitectures. Here we review the current understanding of these species at well-defined interfaces, disclosing exquisite insights into their structural and chemical properties, and also discussing methods by which to manipulate their intramolecular and organizational features. The distinct characteristics arising from the interfacial confinement offer intriguing prospects for molecular science and advanced materials. We assess the role of surface interactions with respect to electronic and physicochemical characteristics, and describe in situ metallation pathways, molecular magnetism, rotation and switching. The engineering of nanostructures, organized layers, interfacial hybrid and bio-inspired systems is also addressed.