Determination of Quantum Chemistry Based Force Fields for Molecular Dynamics Simulations of Aromatic Polymers

NASA Technical Reports Server (NTRS)

Jaffe, Richard; Langhoff, Stephen R. (Technical Monitor)

1995-01-01

Ab initio quantum chemistry calculations for model molecules can be used to parameterize force fields for molecular dynamics simulations of polymers. Emphasis in our research group is on using quantum chemistry-based force fields for molecular dynamics simulations of organic polymers in the melt and glassy states, but the methodology is applicable to simulations of small molecules, multicomponent systems and solutions. Special attention is paid to deriving reliable descriptions of the non-bonded and electrostatic interactions. Several procedures have been developed for deriving and calibrating these parameters. Our force fields for aromatic polyimide simulations will be described. In this application, the intermolecular interactions are the critical factor in determining many properties of the polymer (including its color).

Mirrored continuum and molecular scale simulations of the ignition of high-pressure phases of RDX

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

Lee, Kibaek; Stewart, D. Scott, E-mail: santc@illinois.edu, E-mail: dss@illinois.edu; Joshi, Kaushik

2016-05-14

We present a mirrored atomistic and continuum framework that is used to describe the ignition of energetic materials, and a high-pressure phase of RDX in particular. The continuum formulation uses meaningful averages of thermodynamic properties obtained from the atomistic simulation and a simplification of enormously complex reaction kinetics. In particular, components are identified based on molecular weight bin averages and our methodology assumes that both the averaged atomistic and continuum simulations are represented on the same time and length scales. The atomistic simulations of thermally initiated ignition of RDX are performed using reactive molecular dynamics (RMD). The continuum model ismore » based on multi-component thermodynamics and uses a kinetics scheme that describes observed chemical changes of the averaged atomistic simulations. Thus the mirrored continuum simulations mimic the rapid change in pressure, temperature, and average molecular weight of species in the reactive mixture. This mirroring enables a new technique to simplify the chemistry obtained from reactive MD simulations while retaining the observed features and spatial and temporal scales from both the RMD and continuum model. The primary benefit of this approach is a potentially powerful, but familiar way to interpret the atomistic simulations and understand the chemical events and reaction rates. The approach is quite general and thus can provide a way to model chemistry based on atomistic simulations and extend the reach of those simulations.« less

Quantum Fragment Based ab Initio Molecular Dynamics for Proteins.

PubMed

Liu, Jinfeng; Zhu, Tong; Wang, Xianwei; He, Xiao; Zhang, John Z H

2015-12-08

Developing ab initio molecular dynamics (AIMD) methods for practical application in protein dynamics is of significant interest. Due to the large size of biomolecules, applying standard quantum chemical methods to compute energies for dynamic simulation is computationally prohibitive. In this work, a fragment based ab initio molecular dynamics approach is presented for practical application in protein dynamics study. In this approach, the energy and forces of the protein are calculated by a recently developed electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. For simulation in explicit solvent, mechanical embedding is introduced to treat protein interaction with explicit water molecules. This AIMD approach has been applied to MD simulations of a small benchmark protein Trpcage (with 20 residues and 304 atoms) in both the gas phase and in solution. Comparison to the simulation result using the AMBER force field shows that the AIMD gives a more stable protein structure in the simulation, indicating that quantum chemical energy is more reliable. Importantly, the present fragment-based AIMD simulation captures quantum effects including electrostatic polarization and charge transfer that are missing in standard classical MD simulations. The current approach is linear-scaling, trivially parallel, and applicable to performing the AIMD simulation of proteins with a large size.

Novel Breast Cancer Therapeutics Based on Bacterial Cupredoxin

DTIC Science & Technology

2008-09-01

M. and Lim, C. (1999) Exploring the dynamic information content of a protein NMR structure: comparison of a molecular dynamics simulation with the...crowding has structural effects on the folded ensemble of polypeptides. energy landscape theory excluded volume effect molecular simulations protein... molecular simulations (51). Thermo- dynamic properties such as the radius of gyration (Rg), shape parameters ( and S) (11), and the fraction of native

Specific interactions between mycobacterial FtsZ protein and curcumin derivatives: Molecular docking and ab initio molecular simulations

NASA Astrophysics Data System (ADS)

Fujimori, Mitsuki; Sogawa, Haruki; Ota, Shintaro; Karpov, Pavel; Shulga, Sergey; Blume, Yaroslav; Kurita, Noriyuki

2018-01-01

Filamentous temperature-sensitive Z (FtsZ) protein plays essential role in bacteria cell division, and its inhibition prevents Mycobacteria reproduction. Here we adopted curcumin derivatives as candidates of novel inhibitors and investigated their specific interactions with FtsZ, using ab initio molecular simulations based on protein-ligand docking, classical molecular mechanics and ab initio fragment molecular orbital (FMO) calculations. Based on FMO calculations, we specified the most preferable site of curcumin binding to FtsZ and highlighted the key amino acid residues for curcumin binding at an electronic level. The result will be useful for proposing novel inhibitors against FtsZ based on curcumin derivatives.

Local-feature analysis for automated coarse-graining of bulk-polymer molecular dynamics simulations.

PubMed

Xue, Y; Ludovice, P J; Grover, M A

2012-12-01

A method for automated coarse-graining of bulk polymers is presented, using the data-mining tool of local feature analysis. Most existing methods for polymer coarse-graining define superatoms based on their covalent bonding topology along the polymer backbone, but here superatoms are defined based only on their correlated motions, as observed in molecular dynamics simulations. Correlated atomic motions are identified in the simulation data using local feature analysis, between atoms in the same or in different polymer chains. Groups of highly correlated atoms constitute the superatoms in the coarse-graining scheme, and the positions of their seed coordinates are then projected forward in time. Based on only the seed positions, local feature analysis enables the full reconstruction of all atomic positions. This reconstruction suggests an iterative scheme to reduce the computation of the simulations to initialize another short molecular dynamic simulation, identify new superatoms, and again project forward in time.

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

DOE PAGES

Petsev, Nikolai Dimitrov; Leal, L. Gary; Shell, M. Scott

2017-12-21

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely-resolved (e.g. molecular dynamics) and coarse-grained (e.g. continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 84115 (2016)], simulatedmore » using a particle-based continuum method known as smoothed dissipative particle dynamics (SDPD). An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.« less

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

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

Petsev, Nikolai Dimitrov; Leal, L. Gary; Shell, M. Scott

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely-resolved (e.g. molecular dynamics) and coarse-grained (e.g. continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 84115 (2016)], simulatedmore » using a particle-based continuum method known as smoothed dissipative particle dynamics (SDPD). An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.« less

A reduced basis method for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Vincent-Finley, Rachel Elisabeth

In this dissertation, we develop a method for molecular simulation based on principal component analysis (PCA) of a molecular dynamics trajectory and least squares approximation of a potential energy function. Molecular dynamics (MD) simulation is a computational tool used to study molecular systems as they evolve through time. With respect to protein dynamics, local motions, such as bond stretching, occur within femtoseconds, while rigid body and large-scale motions, occur within a range of nanoseconds to seconds. To capture motion at all levels, time steps on the order of a femtosecond are employed when solving the equations of motion and simulations must continue long enough to capture the desired large-scale motion. To date, simulations of solvated proteins on the order of nanoseconds have been reported. It is typically the case that simulations of a few nanoseconds do not provide adequate information for the study of large-scale motions. Thus, the development of techniques that allow longer simulation times can advance the study of protein function and dynamics. In this dissertation we use principal component analysis (PCA) to identify the dominant characteristics of an MD trajectory and to represent the coordinates with respect to these characteristics. We augment PCA with an updating scheme based on a reduced representation of a molecule and consider equations of motion with respect to the reduced representation. We apply our method to butane and BPTI and compare the results to standard MD simulations of these molecules. Our results indicate that the molecular activity with respect to our simulation method is analogous to that observed in the standard MD simulation with simulations on the order of picoseconds.

pysimm: A Python Package for Simulation of Molecular Systems

NASA Astrophysics Data System (ADS)

Fortunato, Michael; Colina, Coray

pysimm, short for python simulation interface for molecular modeling, is a python package designed to facilitate the structure generation and simulation of molecular systems through convenient and programmatic access to object-oriented representations of molecular system data. This poster presents core features of pysimm and design philosophies that highlight a generalized methodology for incorporation of third-party software packages through API interfaces. The integration with the LAMMPS simulation package is explained to demonstrate this methodology. pysimm began as a back-end python library that powered a cloud-based application on nanohub.org for amorphous polymer simulation. The extension from a specific application library to general purpose simulation interface is explained. Additionally, this poster highlights the rapid development of new applications to construct polymer chains capable of controlling chain morphology such as molecular weight distribution and monomer composition.

wFReDoW: A Cloud-Based Web Environment to Handle Molecular Docking Simulations of a Fully Flexible Receptor Model

PubMed Central

De Paris, Renata; Frantz, Fábio A.; Norberto de Souza, Osmar; Ruiz, Duncan D. A.

2013-01-01

Molecular docking simulations of fully flexible protein receptor (FFR) models are coming of age. In our studies, an FFR model is represented by a series of different conformations derived from a molecular dynamic simulation trajectory of the receptor. For each conformation in the FFR model, a docking simulation is executed and analyzed. An important challenge is to perform virtual screening of millions of ligands using an FFR model in a sequential mode since it can become computationally very demanding. In this paper, we propose a cloud-based web environment, called web Flexible Receptor Docking Workflow (wFReDoW), which reduces the CPU time in the molecular docking simulations of FFR models to small molecules. It is based on the new workflow data pattern called self-adaptive multiple instances (P-SaMIs) and on a middleware built on Amazon EC2 instances. P-SaMI reduces the number of molecular docking simulations while the middleware speeds up the docking experiments using a High Performance Computing (HPC) environment on the cloud. The experimental results show a reduction in the total elapsed time of docking experiments and the quality of the new reduced receptor models produced by discarding the nonpromising conformations from an FFR model ruled by the P-SaMI data pattern. PMID:23691504

Convergence and reproducibility in molecular dynamics simulations of the DNA duplex d(GCACGAACGAACGAACGC).

PubMed

Galindo-Murillo, Rodrigo; Roe, Daniel R; Cheatham, Thomas E

2015-05-01

The structure and dynamics of DNA are critically related to its function. Molecular dynamics simulations augment experiment by providing detailed information about the atomic motions. However, to date the simulations have not been long enough for convergence of the dynamics and structural properties of DNA. Molecular dynamics simulations performed with AMBER using the ff99SB force field with the parmbsc0 modifications, including ensembles of independent simulations, were compared to long timescale molecular dynamics performed with the specialized Anton MD engine on the B-DNA structure d(GCACGAACGAACGAACGC). To assess convergence, the decay of the average RMSD values over longer and longer time intervals was evaluated in addition to assessing convergence of the dynamics via the Kullback-Leibler divergence of principal component projection histograms. These molecular dynamics simulations-including one of the longest simulations of DNA published to date at ~44μs-surprisingly suggest that the structure and dynamics of the DNA helix, neglecting the terminal base pairs, are essentially fully converged on the ~1-5μs timescale. We can now reproducibly converge the structure and dynamics of B-DNA helices, omitting the terminal base pairs, on the μs time scale with both the AMBER and CHARMM C36 nucleic acid force fields. Results from independent ensembles of simulations starting from different initial conditions, when aggregated, match the results from long timescale simulations on the specialized Anton MD engine. With access to large-scale GPU resources or the specialized MD engine "Anton" it is possible for a variety of molecular systems to reproducibly and reliably converge the conformational ensemble of sampled structures. This article is part of a Special Issue entitled: Recent developments of molecular dynamics. Copyright © 2014. Published by Elsevier B.V.

Ab initio molecular simulations on specific interactions between amyloid beta and monosaccharides

NASA Astrophysics Data System (ADS)

Nomura, Kazuya; Okamoto, Akisumi; Yano, Atsushi; Higai, Shin'ichi; Kondo, Takashi; Kamba, Seiji; Kurita, Noriyuki

2012-09-01

Aggregation of amyloid β (Aβ) peptides, which is a key pathogenetic event in Alzheimer's disease, can be caused by cell-surface saccharides. We here investigated stable structures of the solvated complexes of Aβ with some types of monosaccharides using molecular simulations based on protein-ligand docking and classical molecular mechanics methods. Moreover, the specific interactions between Aβ and the monosaccharides were elucidated at an electronic level by ab initio fragment molecular orbital calculations. Based on the results, we proposed which type of monosaccharide prefers to have large binding affinity to Aβ and inhibit the Aβ aggregation.

Prediction of Protein-Peptide Interactions: Application of the XPairIT to Anthrax Lethal Factor and Substrates

DTIC Science & Technology

2013-09-01

hydrogen bonds in Tyrosine-containing peptides. Dalkas et al[7] used docking and molecular dynamics simulations to study a variety of MAPKK-based... simulated using NAMD molecular dynamics and the CHARMM[20] forcefield at 300K and employing the Generalized Born Implicit Solvent (GBIS[21]) with the...which were reported in Section 2. Specifically, after a ~10ns molecular dynamics simulation in TIP3 explicit water, significant motion of domains III

Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

PubMed

John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

2012-01-01

Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

Predicting RNA Duplex Dimerization Free-Energy Changes upon Mutations Using Molecular Dynamics Simulations.

PubMed

Sakuraba, Shun; Asai, Kiyoshi; Kameda, Tomoshi

2015-11-05

The dimerization free energies of RNA-RNA duplexes are fundamental values that represent the structural stability of RNA complexes. We report a comparative analysis of RNA-RNA duplex dimerization free-energy changes upon mutations, estimated from a molecular dynamics simulation and experiments. A linear regression for nine pairs of double-stranded RNA sequences, six base pairs each, yielded a mean absolute deviation of 0.55 kcal/mol and an R(2) value of 0.97, indicating quantitative agreement between simulations and experimental data. The observed accuracy indicates that the molecular dynamics simulation with the current molecular force field is capable of estimating the thermodynamic properties of RNA molecules.

Combined quantum-mechanics/molecular-mechanics dynamics simulation of A-DNA double strands irradiated by ultra-low-energy carbon ions

NASA Astrophysics Data System (ADS)

Ngaojampa, C.; Nimmanpipug, P.; Yu, L. D.; Anuntalabhochai, S.; Lee, V. S.

2011-02-01

In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by <200 eV carbon ions were performed to investigate the molecular implications of mutation bias. The simulations were focused on the responses of the DNA backbones and nitrogenous bases to irradiation. Analyses of the root mean square displacements of the backbones and non-hydrogen atoms of base rings of the simulated DNA structure after irradiation revealed a potential preference of DNA double strand separation, dependent on the irradiating energy. The results show that for the backbones, the large difference in the displacement between poly-GC and poly-AT in the initial time period could be the reason for the backbone breakage; for the nitrogenous base pairs, A-T is 30% more sensitive or vulnerable to ion irradiation than G-C, demonstrating a preferential, instead of random, effect of irradiation-induced mutation.

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

PubMed Central

Baumketner, Andrij

2009-01-01

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

III-Nitride, SiC and Diamond Materials for Electronic Devices. Symposium Held April 8-12 1996, San Francisco, California, U.S.A. Volume 423.

DTIC Science & Technology

1996-12-01

gallium, nitrogen and gallium nitride structures. Thus it can be shown to be transferable and efficient for predictive molecular -dynamic simulations on...potentials and forces for the molecular dynamics simulations are derived by means of a density-functional based nonorthogonal tight-binding (DF-TB) scheme...LDA). Molecular -dynamics simulations for determining the different reconstructions of the SiC surface use the slab method (two-dimensional periodic

Why should biochemistry students be introduced to molecular dynamics simulations--and how can we introduce them?

PubMed

Elmore, Donald E

2016-01-01

Molecular dynamics (MD) simulations play an increasingly important role in many aspects of biochemical research but are often not part of the biochemistry curricula at the undergraduate level. This article discusses the pedagogical value of exposing students to MD simulations and provides information to help instructors consider what software and hardware resources are necessary to successfully introduce these simulations into their courses. In addition, a brief review of the MD-based activities in this issue and other sources are provided. © 2016 The International Union of Biochemistry and Molecular Biology.

Multi-scale modelling of supercapacitors: From molecular simulations to a transmission line model

NASA Astrophysics Data System (ADS)

Pean, C.; Rotenberg, B.; Simon, P.; Salanne, M.

2016-09-01

We perform molecular dynamics simulations of a typical nanoporous-carbon based supercapacitor. The organic electrolyte consists in 1-ethyl-3-methylimidazolium and hexafluorophosphate ions dissolved in acetonitrile. We simulate systems at equilibrium, for various applied voltages. This allows us to determine the relevant thermodynamic (capacitance) and transport (in-pore resistivities) properties. These quantities are then injected in a transmission line model for testing its ability to predict the charging properties of the device. The results from this macroscopic model are in good agreement with non-equilibrium molecular dynamics simulations, which validates its use for interpreting electrochemical impedance experiments.

Sampling enhancement for the quantum mechanical potential based molecular dynamics simulations: a general algorithm and its extension for free energy calculation on rugged energy surface.

PubMed

Li, Hongzhi; Yang, Wei

2007-03-21

An approach is developed in the replica exchange framework to enhance conformational sampling for the quantum mechanical (QM) potential based molecular dynamics simulations. Importantly, with our enhanced sampling treatment, a decent convergence for electronic structure self-consistent-field calculation is robustly guaranteed, which is made possible in our replica exchange design by avoiding direct structure exchanges between the QM-related replicas and the activated (scaled by low scaling parameters or treated with high "effective temperatures") molecular mechanical (MM) replicas. Although the present approach represents one of the early efforts in the enhanced sampling developments specifically for quantum mechanical potentials, the QM-based simulations treated with the present technique can possess the similar sampling efficiency to the MM based simulations treated with the Hamiltonian replica exchange method (HREM). In the present paper, by combining this sampling method with one of our recent developments (the dual-topology alchemical HREM approach), we also introduce a method for the sampling enhanced QM-based free energy calculations.

MaMiCo: Software design for parallel molecular-continuum flow simulations

NASA Astrophysics Data System (ADS)

Neumann, Philipp; Flohr, Hanno; Arora, Rahul; Jarmatz, Piet; Tchipev, Nikola; Bungartz, Hans-Joachim

2016-03-01

The macro-micro-coupling tool (MaMiCo) was developed to ease the development of and modularize molecular-continuum simulations, retaining sequential and parallel performance. We demonstrate the functionality and performance of MaMiCo by coupling the spatially adaptive Lattice Boltzmann framework waLBerla with four molecular dynamics (MD) codes: the light-weight Lennard-Jones-based implementation SimpleMD, the node-level optimized software ls1 mardyn, and the community codes ESPResSo and LAMMPS. We detail interface implementations to connect each solver with MaMiCo. The coupling for each waLBerla-MD setup is validated in three-dimensional channel flow simulations which are solved by means of a state-based coupling method. We provide sequential and strong scaling measurements for the four molecular-continuum simulations. The overhead of MaMiCo is found to come at 10%-20% of the total (MD) runtime. The measurements further show that scalability of the hybrid simulations is reached on up to 500 Intel SandyBridge, and more than 1000 AMD Bulldozer compute cores.

A molecular fragment cheminformatics roadmap for mesoscopic simulation.

PubMed

Truszkowski, Andreas; Daniel, Mirco; Kuhn, Hubert; Neumann, Stefan; Steinbeck, Christoph; Zielesny, Achim; Epple, Matthias

2014-12-01

Mesoscopic simulation studies the structure, dynamics and properties of large molecular ensembles with millions of atoms: Its basic interacting units (beads) are no longer the nuclei and electrons of quantum chemical ab-initio calculations or the atom types of molecular mechanics but molecular fragments, molecules or even larger molecular entities. For its simulation setup and output a mesoscopic simulation kernel software uses abstract matrix (array) representations for bead topology and connectivity. Therefore a pure kernel-based mesoscopic simulation task is a tedious, time-consuming and error-prone venture that limits its practical use and application. A consequent cheminformatics approach tackles these problems and provides solutions for a considerably enhanced accessibility. This study aims at outlining a complete cheminformatics roadmap that frames a mesoscopic Molecular Fragment Dynamics (MFD) simulation kernel to allow its efficient use and practical application. The molecular fragment cheminformatics roadmap consists of four consecutive building blocks: An adequate fragment structure representation (1), defined operations on these fragment structures (2), the description of compartments with defined compositions and structural alignments (3), and the graphical setup and analysis of a whole simulation box (4). The basis of the cheminformatics approach (i.e. building block 1) is a SMILES-like line notation (denoted f SMILES) with connected molecular fragments to represent a molecular structure. The f SMILES notation and the following concepts and methods for building blocks 2-4 are outlined with examples and practical usage scenarios. It is shown that the requirements of the roadmap may be partly covered by already existing open-source cheminformatics software. Mesoscopic simulation techniques like MFD may be considerably alleviated and broadened for practical use with a consequent cheminformatics layer that successfully tackles its setup subtleties and conceptual usage hurdles. Molecular Fragment Cheminformatics may be regarded as a crucial accelerator to propagate MFD and similar mesoscopic simulation techniques in the molecular sciences. Graphical abstractA molecular fragment cheminformatics roadmap for mesoscopic simulation.

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.

A novel energy conversion based method for velocity correction in molecular dynamics simulations

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

Jin, Hanhui; Collaborative Innovation Center of Advanced Aero-Engine, Hangzhou 310027; Liu, Ningning

2017-05-01

Molecular dynamics (MD) simulation has become an important tool for studying micro- or nano-scale dynamics and the statistical properties of fluids and solids. In MD simulations, there are mainly two approaches: equilibrium and non-equilibrium molecular dynamics (EMD and NEMD). In this paper, a new energy conversion based correction (ECBC) method for MD is developed. Unlike the traditional systematic correction based on macroscopic parameters, the ECBC method is developed strictly based on the physical interaction processes between the pair of molecules or atoms. The developed ECBC method can apply to EMD and NEMD directly. While using MD with this method, themore » difference between the EMD and NEMD is eliminated, and no macroscopic parameters such as external imposed potentials or coefficients are needed. With this method, many limits of using MD are lifted. The application scope of MD is greatly extended.« less

A Direct, Quantitative Connection between Molecular Dynamics Simulations and Vibrational Probe Line Shapes.

PubMed

Xu, Rosalind J; Blasiak, Bartosz; Cho, Minhaeng; Layfield, Joshua P; Londergan, Casey H

2018-05-17

A quantitative connection between molecular dynamics simulations and vibrational spectroscopy of probe-labeled systems would enable direct translation of experimental data into structural and dynamical information. To constitute this connection, all-atom molecular dynamics (MD) simulations were performed for two SCN probe sites (solvent-exposed and buried) in a calmodulin-target peptide complex. Two frequency calculation approaches with substantial nonelectrostatic components, a quantum mechanics/molecular mechanics (QM/MM)-based technique and a solvatochromic fragment potential (SolEFP) approach, were used to simulate the infrared probe line shapes. While QM/MM results disagreed with experiment, SolEFP results matched experimental frequencies and line shapes and revealed the physical and dynamic bases for the observed spectroscopic behavior. The main determinant of the CN probe frequency is the exchange repulsion between the probe and its local structural neighbors, and there is a clear dynamic explanation for the relatively broad probe line shape observed at the "buried" probe site. This methodology should be widely applicable to vibrational probes in many environments.

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

PubMed Central

Zhou, Yu-Ping; Jiang, Jin-Wu

2017-01-01

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

Constraint methods that accelerate free-energy simulations of biomolecules.

PubMed

Perez, Alberto; MacCallum, Justin L; Coutsias, Evangelos A; Dill, Ken A

2015-12-28

Atomistic molecular dynamics simulations of biomolecules are critical for generating narratives about biological mechanisms. The power of atomistic simulations is that these are physics-based methods that satisfy Boltzmann's law, so they can be used to compute populations, dynamics, and mechanisms. But physical simulations are computationally intensive and do not scale well to the sizes of many important biomolecules. One way to speed up physical simulations is by coarse-graining the potential function. Another way is to harness structural knowledge, often by imposing spring-like restraints. But harnessing external knowledge in physical simulations is problematic because knowledge, data, or hunches have errors, noise, and combinatoric uncertainties. Here, we review recent principled methods for imposing restraints to speed up physics-based molecular simulations that promise to scale to larger biomolecules and motions.

Pressure calculation in hybrid particle-field simulations

NASA Astrophysics Data System (ADS)

Milano, Giuseppe; Kawakatsu, Toshihiro

2010-12-01

In the framework of a recently developed scheme for a hybrid particle-field simulation techniques where self-consistent field (SCF) theory and particle models (molecular dynamics) are combined [J. Chem. Phys. 130, 214106 (2009)], we developed a general formulation for the calculation of instantaneous pressure and stress tensor. The expressions have been derived from statistical mechanical definition of the pressure starting from the expression for the free energy functional in the SCF theory. An implementation of the derived formulation suitable for hybrid particle-field molecular dynamics-self-consistent field simulations is described. A series of test simulations on model systems are reported comparing the calculated pressure with those obtained from standard molecular dynamics simulations based on pair potentials.

Molecular Optical Simulation Environment (MOSE): A Platform for the Simulation of Light Propagation in Turbid Media

PubMed Central

Ren, Shenghan; Chen, Xueli; Wang, Hailong; Qu, Xiaochao; Wang, Ge; Liang, Jimin; Tian, Jie

2013-01-01

The study of light propagation in turbid media has attracted extensive attention in the field of biomedical optical molecular imaging. In this paper, we present a software platform for the simulation of light propagation in turbid media named the “Molecular Optical Simulation Environment (MOSE)”. Based on the gold standard of the Monte Carlo method, MOSE simulates light propagation both in tissues with complicated structures and through free-space. In particular, MOSE synthesizes realistic data for bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and diffuse optical tomography (DOT). The user-friendly interface and powerful visualization tools facilitate data analysis and system evaluation. As a major measure for resource sharing and reproducible research, MOSE aims to provide freeware for research and educational institutions, which can be downloaded at http://www.mosetm.net. PMID:23577215

Design of Energetic Ionic Liquids (Preprint)

DTIC Science & Technology

2008-05-07

mesoscale-level simulations of bulk ionic liquids based upon multiscale coarse graining techniques. 15. SUBJECT TERMS 16. SECURITY...simulations utilizing polarizable force fields, and mesoscale-level simulations of bulk ionic liquids based upon multiscale coarse graining...Simulations of the Energetic Ionic Liquid 1-hydroxyethyl-4-amino-1, 2, 4- triazolium Nitrate (HEATN): Molecular dynamics (MD) simulations have been

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

Rizzi, Silvio; Hereld, Mark; Insley, Joseph

In this work we perform in-situ visualization of molecular dynamics simulations, which can help scientists to visualize simulation output on-the-fly, without incurring storage overheads. We present a case study to couple LAMMPS, the large-scale molecular dynamics simulation code with vl3, our parallel framework for large-scale visualization and analysis. Our motivation is to identify effective approaches for covisualization and exploration of large-scale atomistic simulations at interactive frame rates.We propose a system of coupled libraries and describe its architecture, with an implementation that runs on GPU-based clusters. We present the results of strong and weak scalability experiments, as well as future researchmore » avenues based on our results.« less

Complex molecular assemblies at hand via interactive simulations.

PubMed

Delalande, Olivier; Férey, Nicolas; Grasseau, Gilles; Baaden, Marc

2009-11-30

Studying complex molecular assemblies interactively is becoming an increasingly appealing approach to molecular modeling. Here we focus on interactive molecular dynamics (IMD) as a textbook example for interactive simulation methods. Such simulations can be useful in exploring and generating hypotheses about the structural and mechanical aspects of biomolecular interactions. For the first time, we carry out low-resolution coarse-grain IMD simulations. Such simplified modeling methods currently appear to be more suitable for interactive experiments and represent a well-balanced compromise between an important gain in computational speed versus a moderate loss in modeling accuracy compared to higher resolution all-atom simulations. This is particularly useful for initial exploration and hypothesis development for rare molecular interaction events. We evaluate which applications are currently feasible using molecular assemblies from 1900 to over 300,000 particles. Three biochemical systems are discussed: the guanylate kinase (GK) enzyme, the outer membrane protease T and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors complex involved in membrane fusion. We induce large conformational changes, carry out interactive docking experiments, probe lipid-protein interactions and are able to sense the mechanical properties of a molecular model. Furthermore, such interactive simulations facilitate exploration of modeling parameters for method improvement. For the purpose of these simulations, we have developed a freely available software library called MDDriver. It uses the IMD protocol from NAMD and facilitates the implementation and application of interactive simulations. With MDDriver it becomes very easy to render any particle-based molecular simulation engine interactive. Here we use its implementation in the Gromacs software as an example. Copyright 2009 Wiley Periodicals, Inc.

Relaxation estimation of RMSD in molecular dynamics immunosimulations.

PubMed

Schreiner, Wolfgang; Karch, Rudolf; Knapp, Bernhard; Ilieva, Nevena

2012-01-01

Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of "lagged RMSD-analysis" as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged.

eSBMTools 1.0: enhanced native structure-based modeling tools.

PubMed

Lutz, Benjamin; Sinner, Claude; Heuermann, Geertje; Verma, Abhinav; Schug, Alexander

2013-11-01

Molecular dynamics simulations provide detailed insights into the structure and function of biomolecular systems. Thus, they complement experimental measurements by giving access to experimentally inaccessible regimes. Among the different molecular dynamics techniques, native structure-based models (SBMs) are based on energy landscape theory and the principle of minimal frustration. Typically used in protein and RNA folding simulations, they coarse-grain the biomolecular system and/or simplify the Hamiltonian resulting in modest computational requirements while achieving high agreement with experimental data. eSBMTools streamlines running and evaluating SBM in a comprehensive package and offers high flexibility in adding experimental- or bioinformatics-derived restraints. We present a software package that allows setting up, modifying and evaluating SBM for both RNA and proteins. The implemented workflows include predicting protein complexes based on bioinformatics-derived inter-protein contact information, a standardized setup of protein folding simulations based on the common PDB format, calculating reaction coordinates and evaluating the simulation by free-energy calculations with weighted histogram analysis method or by phi-values. The modules interface with the molecular dynamics simulation program GROMACS. The package is open source and written in architecture-independent Python2. http://sourceforge.net/projects/esbmtools/. alexander.schug@kit.edu. Supplementary data are available at Bioinformatics online.

Compartmental and Spatial Rule-Based Modeling with Virtual Cell.

PubMed

Blinov, Michael L; Schaff, James C; Vasilescu, Dan; Moraru, Ion I; Bloom, Judy E; Loew, Leslie M

2017-10-03

In rule-based modeling, molecular interactions are systematically specified in the form of reaction rules that serve as generators of reactions. This provides a way to account for all the potential molecular complexes and interactions among multivalent or multistate molecules. Recently, we introduced rule-based modeling into the Virtual Cell (VCell) modeling framework, permitting graphical specification of rules and merger of networks generated automatically (using the BioNetGen modeling engine) with hand-specified reaction networks. VCell provides a number of ordinary differential equation and stochastic numerical solvers for single-compartment simulations of the kinetic systems derived from these networks, and agent-based network-free simulation of the rules. In this work, compartmental and spatial modeling of rule-based models has been implemented within VCell. To enable rule-based deterministic and stochastic spatial simulations and network-free agent-based compartmental simulations, the BioNetGen and NFSim engines were each modified to support compartments. In the new rule-based formalism, every reactant and product pattern and every reaction rule are assigned locations. We also introduce the rule-based concept of molecular anchors. This assures that any species that has a molecule anchored to a predefined compartment will remain in this compartment. Importantly, in addition to formulation of compartmental models, this now permits VCell users to seamlessly connect reaction networks derived from rules to explicit geometries to automatically generate a system of reaction-diffusion equations. These may then be simulated using either the VCell partial differential equations deterministic solvers or the Smoldyn stochastic simulator. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Is an intuitive convergence definition of molecular dynamics simulations solely based on the root mean square deviation possible?

PubMed

Knapp, B; Frantal, S; Cibena, M; Schreiner, W; Bauer, P

2011-08-01

Molecular dynamics is a commonly used technique in computational biology. One key issue of each molecular dynamics simulation is: When does this simulation reach equilibrium state? A widely used way to determine this is the visual and intuitive inspection of root mean square deviation (RMSD) plots of the simulation. Although this technique has been criticized several times, it is still often used. Therefore, we present a study proving that this method is not reliable at all. We conducted a survey with participants from the field in which we illustrated different RMSD plots to scientists in the field of molecular dynamics. These plots were randomized and repeated, using a statistical model and different variants of the plots. We show that there is no mutual consent about the point of equilibrium. The decisions are severely biased by different parameters. Therefore, we conclude that scientists should not discuss the equilibration of a molecular dynamics simulation on the basis of a RMSD plot.

ls1 mardyn: The Massively Parallel Molecular Dynamics Code for Large Systems.

PubMed

Niethammer, Christoph; Becker, Stefan; Bernreuther, Martin; Buchholz, Martin; Eckhardt, Wolfgang; Heinecke, Alexander; Werth, Stephan; Bungartz, Hans-Joachim; Glass, Colin W; Hasse, Hans; Vrabec, Jadran; Horsch, Martin

2014-10-14

The molecular dynamics simulation code ls1 mardyn is presented. It is a highly scalable code, optimized for massively parallel execution on supercomputing architectures and currently holds the world record for the largest molecular simulation with over four trillion particles. It enables the application of pair potentials to length and time scales that were previously out of scope for molecular dynamics simulation. With an efficient dynamic load balancing scheme, it delivers high scalability even for challenging heterogeneous configurations. Presently, multicenter rigid potential models based on Lennard-Jones sites, point charges, and higher-order polarities are supported. Due to its modular design, ls1 mardyn can be extended to new physical models, methods, and algorithms, allowing future users to tailor it to suit their respective needs. Possible applications include scenarios with complex geometries, such as fluids at interfaces, as well as nonequilibrium molecular dynamics simulation of heat and mass transfer.

Molecular Simulation Results on Charged Carbon Nanotube Forest-Based Supercapacitors.

PubMed

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

2018-06-22

Electrochemical double-layer capacitances of charged carbon nanotube (CNT) forests with tetraethyl ammonium tetrafluoro borate electrolyte in propylene carbonate are studied on the basis of molecular dynamics simulation. Direct molecular simulation of the filling of pore spaces of the forest is feasible even with realistic, small CNT spacings. The numerical solution of the Poisson equation based on the extracted average charge densities then yields a regular experimental dependence on the width of the pore spaces, in contrast to the anomalous pattern observed in experiments on other carbon materials and also in simulations on planar slot-like pores. The capacitances obtained have realistic magnitudes but are insensitive to electric potential differences between the electrodes in this model. This agrees with previous calculations on CNT forest supercapacitors, but not with experiments which have suggested electrochemical doping for these systems. Those phenomena remain for further theory/modeling work. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-temperature model in molecular dynamics simulations of cascades in Ni-based alloys

DOE PAGES

Zarkadoula, Eva; Samolyuk, German; Weber, William J.

2017-01-03

In high-energy irradiation events, energy from the fast moving ion is transferred to the system via nuclear and electronic energy loss mechanisms. The nuclear energy loss results in the creation of point defects and clusters, while the energy transferred to the electrons results in the creation of high electronic temperatures, which can affect the damage evolution. In this paper, we perform molecular dynamics simulations of 30 keV and 50 keV Ni ion cascades in nickel-based alloys without and with the electronic effects taken into account. We compare the results of classical molecular dynamics (MD) simulations, where the electronic effects aremore » ignored, with results from simulations that include the electronic stopping only, as well as simulations where both the electronic stopping and the electron-phonon coupling are incorporated, as described by the two temperature model (2T-MD). Finally, our results indicate that the 2T-MD leads to a smaller amount of damage, more isolated defects and smaller defect clusters.« less

Formation of fivefold deformation twins in nanocrystalline face-centered-cubic copper based on molecular dynamics simulations

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

Cao, A. J.; Wei, Y. G.

2006-07-24

Fivefold deformation twins were reported recently to be observed in the experiment of the nanocrystalline face-centered-cubic metals and alloys. However, they were not predicted previously based on the molecular dynamics (MD) simulations and the reason was thought to be a uniaxial tension considered in the simulations. In the present investigation, through introducing pretwins in grain regions, using the MD simulations, the authors predict out the fivefold deformation twins in the grain regions of the nanocrystal grain cell, which undergoes a uniaxial tension. It is shown in their simulation results that series of Shockley partial dislocations emitted from grain boundaries providemore » sequential twining mechanism, which results in fivefold deformation twins.« less

Relaxation Estimation of RMSD in Molecular Dynamics Immunosimulations

PubMed Central

Schreiner, Wolfgang; Karch, Rudolf; Knapp, Bernhard; Ilieva, Nevena

2012-01-01

Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of “lagged RMSD-analysis” as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged. PMID:23019425

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.

Optimizing legacy molecular dynamics software with directive-based offload

DOE PAGES

Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; ...

2015-05-14

The 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 our paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We also 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 resultmore » in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMAS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel (R) Xeon Phi (TM) 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. (C) 2015 Elsevier B.V. All rights reserved.« less

Simulation of size-exclusion chromatography distribution coefficients of comb-shaped molecules in spherical pores comparison of simulation and experiment.

PubMed

Radke, Wolfgang

2004-03-05

Simulations of the distribution coefficients of linear polymers and regular combs with various spacings between the arms have been performed. The distribution coefficients were plotted as a function of the number of segments in order to compare the size exclusion chromatography (SEC)-elution behavior of combs relative to linear molecules. By comparing the simulated SEC-calibration curves it is possible to predict the elution behavior of comb-shaped polymers relative to linear ones. In order to compare the results obtained by computer simulations with experimental data, a variety of comb-shaped polymers varying in side chain length, spacing between the side chains and molecular weights of the backbone were analyzed by SEC with light-scattering detection. It was found that the computer simulations could predict the molecular weights of linear molecules having the same retention volume with an accuracy of about 10%, i.e. the error in the molecular weight obtained by calculating the molecular weight of the comb-polymer based on a calibration curve constructed using linear standards and the results of the computer simulations are of the same magnitude as the experimental error of absolute molecular weight determination.

Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

PubMed

Islam, Md Ataul; Pillay, Tahir S

2017-08-01

In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB. © 2017 John Wiley & Sons A/S.

Molecular dynamics studies of a hexameric purine nucleoside phosphorylase.

PubMed

Zanchi, Fernando Berton; Caceres, Rafael Andrade; Stabeli, Rodrigo Guerino; de Azevedo, Walter Filgueira

2010-03-01

Purine nucleoside phosphorylase (PNP) (EC.2.4.2.1) is an enzyme that catalyzes the cleavage of N-ribosidic bonds of the purine ribonucleosides and 2-deoxyribonucleosides in the presence of inorganic orthophosphate as a second substrate. This enzyme is involved in purine-salvage pathway and has been proposed as a promising target for design and development of antimalarial and antibacterial drugs. Recent elucidation of the three-dimensional structure of PNP by X-ray protein crystallography left open the possibility of structure-based virtual screening initiatives in combination with molecular dynamics simulations focused on identification of potential new antimalarial drugs. Most of the previously published molecular dynamics simulations of PNP were carried out on human PNP, a trimeric PNP. The present article describes for the first time molecular dynamics simulations of hexameric PNP from Plasmodium falciparum (PfPNP). Two systems were simulated in the present work, PfPNP in ligand free form, and in complex with immucillin and sulfate. Based on the dynamical behavior of both systems the main results related to structural stability and protein-drug interactions are discussed.

Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts.

PubMed

Boomsma, Wouter; Tian, Pengfei; Frellsen, Jes; Ferkinghoff-Borg, Jesper; Hamelryck, Thomas; Lindorff-Larsen, Kresten; Vendruscolo, Michele

2014-09-23

Methods of protein structure determination based on NMR chemical shifts are becoming increasingly common. The most widely used approaches adopt the molecular fragment replacement strategy, in which structural fragments are repeatedly reassembled into different complete conformations in molecular simulations. Although these approaches are effective in generating individual structures consistent with the chemical shift data, they do not enable the sampling of the conformational space of proteins with correct statistical weights. Here, we present a method of molecular fragment replacement that makes it possible to perform equilibrium simulations of proteins, and hence to determine their free energy landscapes. This strategy is based on the encoding of the chemical shift information in a probabilistic model in Markov chain Monte Carlo simulations. First, we demonstrate that with this approach it is possible to fold proteins to their native states starting from extended structures. Second, we show that the method satisfies the detailed balance condition and hence it can be used to carry out an equilibrium sampling from the Boltzmann distribution corresponding to the force field used in the simulations. Third, by comparing the results of simulations carried out with and without chemical shift restraints we describe quantitatively the effects that these restraints have on the free energy landscapes of proteins. Taken together, these results demonstrate that the molecular fragment replacement strategy can be used in combination with chemical shift information to characterize not only the native structures of proteins but also their conformational fluctuations.

Toward prethreshold gate-based quantum simulation of chemical dynamics: using potential energy surfaces to simulate few-channel molecular collisions

DOE PAGES

Sornborger, Andrew Tyler; Stancil, Phillip; Geller, Michael R.

2018-03-22

Here, one of the most promising applications of an error-corrected universal quantum computer is the efficient simulation of complex quantum systems such as large molecular systems. In this application, one is interested in both the electronic structure such as the ground state energy and dynamical properties such as the scattering cross section and chemical reaction rates. However, most theoretical work and experimental demonstrations have focused on the quantum computation of energies and energy surfaces. In this work, we attempt to make the prethreshold (not error-corrected) quantum simulation of dynamical properties practical as well. We show that the use of precomputedmore » potential energy surfaces and couplings enables the gate-based simulation of few-channel but otherwise realistic molecular collisions. Our approach is based on the widely used Born–Oppenheimer approximation for the structure problem coupled with a semiclassical method for the dynamics. In the latter the electrons are treated quantum mechanically but the nuclei are classical, which restricts the collisions to high energy or temperature (typically above ≈10 eV). By using operator splitting techniques optimized for the resulting time-dependent Hamiltonian simulation problem, we give several physically realistic collision examples, with 3–8 channels and circuit depths < 1000.« less

Toward prethreshold gate-based quantum simulation of chemical dynamics: using potential energy surfaces to simulate few-channel molecular collisions

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

Sornborger, Andrew Tyler; Stancil, Phillip; Geller, Michael R.

Here, one of the most promising applications of an error-corrected universal quantum computer is the efficient simulation of complex quantum systems such as large molecular systems. In this application, one is interested in both the electronic structure such as the ground state energy and dynamical properties such as the scattering cross section and chemical reaction rates. However, most theoretical work and experimental demonstrations have focused on the quantum computation of energies and energy surfaces. In this work, we attempt to make the prethreshold (not error-corrected) quantum simulation of dynamical properties practical as well. We show that the use of precomputedmore » potential energy surfaces and couplings enables the gate-based simulation of few-channel but otherwise realistic molecular collisions. Our approach is based on the widely used Born–Oppenheimer approximation for the structure problem coupled with a semiclassical method for the dynamics. In the latter the electrons are treated quantum mechanically but the nuclei are classical, which restricts the collisions to high energy or temperature (typically above ≈10 eV). By using operator splitting techniques optimized for the resulting time-dependent Hamiltonian simulation problem, we give several physically realistic collision examples, with 3–8 channels and circuit depths < 1000.« less

Toward prethreshold gate-based quantum simulation of chemical dynamics: using potential energy surfaces to simulate few-channel molecular collisions

NASA Astrophysics Data System (ADS)

Sornborger, Andrew T.; Stancil, Phillip; Geller, Michael R.

2018-05-01

One of the most promising applications of an error-corrected universal quantum computer is the efficient simulation of complex quantum systems such as large molecular systems. In this application, one is interested in both the electronic structure such as the ground state energy and dynamical properties such as the scattering cross section and chemical reaction rates. However, most theoretical work and experimental demonstrations have focused on the quantum computation of energies and energy surfaces. In this work, we attempt to make the prethreshold (not error-corrected) quantum simulation of dynamical properties practical as well. We show that the use of precomputed potential energy surfaces and couplings enables the gate-based simulation of few-channel but otherwise realistic molecular collisions. Our approach is based on the widely used Born-Oppenheimer approximation for the structure problem coupled with a semiclassical method for the dynamics. In the latter the electrons are treated quantum mechanically but the nuclei are classical, which restricts the collisions to high energy or temperature (typically above ≈ 10 eV). By using operator splitting techniques optimized for the resulting time-dependent Hamiltonian simulation problem, we give several physically realistic collision examples, with 3-8 channels and circuit depths < 1000.

Vibrational, spectroscopic, molecular docking and density functional theory studies on N-(5-aminopyridin-2-yl)acetamide

NASA Astrophysics Data System (ADS)

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

2016-12-01

Conformational analysis was carried out for N-(5-aminopyridin-2-yl)acetamide (APA) molecule. The most stable, optimized structure was predicted by the density functional theory calculations using the B3LYP functional with cc-pVQZ basis set. The optimized structural parameters and vibrational frequencies were calculated. The experimental and theoretical vibrational frequencies were assigned and compared. Ultraviolet-visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated. Frontier molecular orbitals and related molecular properties were computed, which reveals that the higher molecular reactivity and stability of the APA molecule and further density of states spectrum was simulated. The natural bond orbital analysis was also performed to confirm the bioactivity of the APA molecule. Antidiabetic activity was studied based on the molecular docking analysis and the APA molecule was identified that it can act as a good inhibitor against diabetic nephropathy.

CABS-flex: server for fast simulation of protein structure fluctuations

PubMed Central

Jamroz, Michal; Kolinski, Andrzej; Kmiecik, Sebastian

2013-01-01

The CABS-flex server (http://biocomp.chem.uw.edu.pl/CABSflex) implements CABS-model–based protocol for the fast simulations of near-native dynamics of globular proteins. In this application, the CABS model was shown to be a computationally efficient alternative to all-atom molecular dynamics—a classical simulation approach. The simulation method has been validated on a large set of molecular dynamics simulation data. Using a single input (user-provided file in PDB format), the CABS-flex server outputs an ensemble of protein models (in all-atom PDB format) reflecting the flexibility of the input structure, together with the accompanying analysis (residue mean-square-fluctuation profile and others). The ensemble of predicted models can be used in structure-based studies of protein functions and interactions. PMID:23658222

CABS-flex: Server for fast simulation of protein structure fluctuations.

PubMed

Jamroz, Michal; Kolinski, Andrzej; Kmiecik, Sebastian

2013-07-01

The CABS-flex server (http://biocomp.chem.uw.edu.pl/CABSflex) implements CABS-model-based protocol for the fast simulations of near-native dynamics of globular proteins. In this application, the CABS model was shown to be a computationally efficient alternative to all-atom molecular dynamics--a classical simulation approach. The simulation method has been validated on a large set of molecular dynamics simulation data. Using a single input (user-provided file in PDB format), the CABS-flex server outputs an ensemble of protein models (in all-atom PDB format) reflecting the flexibility of the input structure, together with the accompanying analysis (residue mean-square-fluctuation profile and others). The ensemble of predicted models can be used in structure-based studies of protein functions and interactions.

An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors.

PubMed

Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

2015-11-16

In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors.

Analysis of factors influencing hydration site prediction based on molecular dynamics simulations.

PubMed

Yang, Ying; Hu, Bingjie; Lill, Markus A

2014-10-27

Water contributes significantly to the binding of small molecules to proteins in biochemical systems. Molecular dynamics (MD) simulation based programs such as WaterMap and WATsite have been used to probe the locations and thermodynamic properties of hydration sites at the surface or in the binding site of proteins generating important information for structure-based drug design. However, questions associated with the influence of the simulation protocol on hydration site analysis remain. In this study, we use WATsite to investigate the influence of factors such as simulation length and variations in initial protein conformations on hydration site prediction. We find that 4 ns MD simulation is appropriate to obtain a reliable prediction of the locations and thermodynamic properties of hydration sites. In addition, hydration site prediction can be largely affected by the initial protein conformations used for MD simulations. Here, we provide a first quantification of this effect and further indicate that similar conformations of binding site residues (RMSD < 0.5 Å) are required to obtain consistent hydration site predictions.

ReaDDy - A Software for Particle-Based Reaction-Diffusion Dynamics in Crowded Cellular Environments

PubMed Central

Schöneberg, Johannes; Noé, Frank

2013-01-01

We introduce the software package ReaDDy for simulation of detailed spatiotemporal mechanisms of dynamical processes in the cell, based on reaction-diffusion dynamics with particle resolution. In contrast to other particle-based reaction kinetics programs, ReaDDy supports particle interaction potentials. This permits effects such as space exclusion, molecular crowding and aggregation to be modeled. The biomolecules simulated can be represented as a sphere, or as a more complex geometry such as a domain structure or polymer chain. ReaDDy bridges the gap between small-scale but highly detailed molecular dynamics or Brownian dynamics simulations and large-scale but little-detailed reaction kinetics simulations. ReaDDy has a modular design that enables the exchange of the computing core by efficient platform-specific implementations or dynamical models that are different from Brownian dynamics. PMID:24040218

Primitive chain network simulations for entangled DNA solutions

NASA Astrophysics Data System (ADS)

Masubuchi, Yuichi; Furuichi, Kenji; Horio, Kazushi; Uneyama, Takashi; Watanabe, Hiroshi; Ianniruberto, Giovanni; Greco, Francesco; Marrucci, Giuseppe

2009-09-01

Molecular theories for polymer rheology are based on conformational dynamics of the polymeric chain. Hence, measurements directly related to molecular conformations appear more appealing than indirect ones obtained from rheology. In this study, primitive chain network simulations are compared to experimental data of entangled DNA solutions [Teixeira et al., Macromolecules 40, 2461 (2007)]. In addition to rheological comparisons of both linear and nonlinear viscoelasticities, a molecular extension measure obtained by Teixeira et al. through fluorescent microscopy is compared to simulations, in terms of both averages and distributions. The influence of flow on conformational distributions has never been simulated for the case of entangled polymers, and how DNA molecular individualism extends to the entangled regime is not known. The linear viscoelastic response and the viscosity growth curve in the nonlinear regime are found in good agreement with data for various DNA concentrations. Conversely, the molecular extension measure shows significant departures, even under equilibrium conditions. The reason for such discrepancies remains unknown.

Virtual Transgenics: Using a Molecular Biology Simulation to Impact Student Academic Achievement and Attitudes

NASA Astrophysics Data System (ADS)

Shegog, Ross; Lazarus, Melanie M.; Murray, Nancy G.; Diamond, Pamela M.; Sessions, Nathalie; Zsigmond, Eva

2012-10-01

The transgenic mouse model is useful for studying the causes and potential cures for human genetic diseases. Exposing high school biology students to laboratory experience in developing transgenic animal models is logistically prohibitive. Computer-based simulation, however, offers this potential in addition to advantages of fidelity and reach. This study describes and evaluates a computer-based simulation to train advanced placement high school science students in laboratory protocols, a transgenic mouse model was produced. A simulation module on preparing a gene construct in the molecular biology lab was evaluated using a randomized clinical control design with advanced placement high school biology students in Mercedes, Texas ( n = 44). Pre-post tests assessed procedural and declarative knowledge, time on task, attitudes toward computers for learning and towards science careers. Students who used the simulation increased their procedural and declarative knowledge regarding molecular biology compared to those in the control condition (both p < 0.005). Significant increases continued to occur with additional use of the simulation ( p < 0.001). Students in the treatment group became more positive toward using computers for learning ( p < 0.001). The simulation did not significantly affect attitudes toward science in general. Computer simulation of complex transgenic protocols have potential to provide a "virtual" laboratory experience as an adjunct to conventional educational approaches.

Density-based clustering of small peptide conformations sampled from a molecular dynamics simulation.

PubMed

Kim, Minkyoung; Choi, Seung-Hoon; Kim, Junhyoung; Choi, Kihang; Shin, Jae-Min; Kang, Sang-Kee; Choi, Yun-Jaie; Jung, Dong Hyun

2009-11-01

This study describes the application of a density-based algorithm to clustering small peptide conformations after a molecular dynamics simulation. We propose a clustering method for small peptide conformations that enables adjacent clusters to be separated more clearly on the basis of neighbor density. Neighbor density means the number of neighboring conformations, so if a conformation has too few neighboring conformations, then it is considered as noise or an outlier and is excluded from the list of cluster members. With this approach, we can easily identify clusters in which the members are densely crowded in the conformational space, and we can safely avoid misclustering individual clusters linked by noise or outliers. Consideration of neighbor density significantly improves the efficiency of clustering of small peptide conformations sampled from molecular dynamics simulations and can be used for predicting peptide structures.

Interactive Design Strategy for a Multi-Functional PAMAM Dendrimer-Based Nano-Therapeutic Using Computational Models and Experimental Analysis

PubMed Central

Lee, Inhan; Williams, Christopher R.; Athey, Brian D.; Baker, James R.

2010-01-01

Molecular dynamics simulations of nano-therapeutics as a final product and of all intermediates in the process of generating a multi-functional nano-therapeutic based on a poly(amidoamine) (PAMAM) dendrimer were performed along with chemical analyses of each of them. The actual structures of the dendrimers were predicted, based on potentiometric titration, gel permeation chromatography, and NMR. The chemical analyses determined the numbers of functional molecules, based on the actual structure of the dendrimer. Molecular dynamics simulations calculated the configurations of the intermediates and the radial distributions of functional molecules, based on their numbers. This interactive process between the simulation results and the chemical analyses provided a further strategy to design the next reaction steps and to gain insight into the products at each chemical reaction step. PMID:20700476

Preserving the Boltzmann ensemble in replica-exchange molecular dynamics.

PubMed

Cooke, Ben; Schmidler, Scott C

2008-10-28

We consider the convergence behavior of replica-exchange molecular dynamics (REMD) [Sugita and Okamoto, Chem. Phys. Lett. 314, 141 (1999)] based on properties of the numerical integrators in the underlying isothermal molecular dynamics (MD) simulations. We show that a variety of deterministic algorithms favored by molecular dynamics practitioners for constant-temperature simulation of biomolecules fail either to be measure invariant or irreducible, and are therefore not ergodic. We then show that REMD using these algorithms also fails to be ergodic. As a result, the entire configuration space may not be explored even in an infinitely long simulation, and the simulation may not converge to the desired equilibrium Boltzmann ensemble. Moreover, our analysis shows that for initial configurations with unfavorable energy, it may be impossible for the system to reach a region surrounding the minimum energy configuration. We demonstrate these failures of REMD algorithms for three small systems: a Gaussian distribution (simple harmonic oscillator dynamics), a bimodal mixture of Gaussians distribution, and the alanine dipeptide. Examination of the resulting phase plots and equilibrium configuration densities indicates significant errors in the ensemble generated by REMD simulation. We describe a simple modification to address these failures based on a stochastic hybrid Monte Carlo correction, and prove that this is ergodic.

From classical to quantum and back: Hamiltonian adaptive resolution path integral, ring polymer, and centroid molecular dynamics

NASA Astrophysics Data System (ADS)

Kreis, Karsten; Kremer, Kurt; Potestio, Raffaello; Tuckerman, Mark E.

2017-12-01

Path integral-based methodologies play a crucial role for the investigation of nuclear quantum effects by means of computer simulations. However, these techniques are significantly more demanding than corresponding classical simulations. To reduce this numerical effort, we recently proposed a method, based on a rigorous Hamiltonian formulation, which restricts the quantum modeling to a small but relevant spatial region within a larger reservoir where particles are treated classically. In this work, we extend this idea and show how it can be implemented along with state-of-the-art path integral simulation techniques, including path-integral molecular dynamics, which allows for the calculation of quantum statistical properties, and ring-polymer and centroid molecular dynamics, which allow the calculation of approximate quantum dynamical properties. To this end, we derive a new integration algorithm that also makes use of multiple time-stepping. The scheme is validated via adaptive classical-path-integral simulations of liquid water. Potential applications of the proposed multiresolution method are diverse and include efficient quantum simulations of interfaces as well as complex biomolecular systems such as membranes and proteins.

Molecular dynamics simulations in hybrid particle-continuum schemes: Pitfalls and caveats

NASA Astrophysics Data System (ADS)

Stalter, S.; Yelash, L.; Emamy, N.; Statt, A.; Hanke, M.; Lukáčová-Medvid'ová, M.; Virnau, P.

2018-03-01

Heterogeneous multiscale methods (HMM) combine molecular accuracy of particle-based simulations with the computational efficiency of continuum descriptions to model flow in soft matter liquids. In these schemes, molecular simulations typically pose a computational bottleneck, which we investigate in detail in this study. We find that it is preferable to simulate many small systems as opposed to a few large systems, and that a choice of a simple isokinetic thermostat is typically sufficient while thermostats such as Lowe-Andersen allow for simulations at elevated viscosity. We discuss suitable choices for time steps and finite-size effects which arise in the limit of very small simulation boxes. We also argue that if colloidal systems are considered as opposed to atomistic systems, the gap between microscopic and macroscopic simulations regarding time and length scales is significantly smaller. We propose a novel reduced-order technique for the coupling to the macroscopic solver, which allows us to approximate a non-linear stress-strain relation efficiently and thus further reduce computational effort of microscopic simulations.

An overview of the utility of population simulation software in molecular ecology.

PubMed

Hoban, Sean

2014-05-01

Stochastic simulation software that simultaneously model genetic, population and environmental processes can inform many topics in molecular ecology. These include forecasting species and community response to environmental change, inferring dispersal ecology, revealing cryptic mating, quantifying past population dynamics, assessing in situ management options and monitoring neutral and adaptive biodiversity change. Advances in population demographic-genetic simulation software, especially with respect to individual life history, landscapes and genetic processes, are transforming and expanding the ways that molecular data can be used. The aim of this review is to explain the roles that such software can play in molecular ecology studies (whether as a principal component or a supporting function) so that researchers can decide whether, when and precisely how simulations can be incorporated into their work. First, I use seven case studies to demonstrate how simulations are employed, their specific advantage/necessity and what alternative or complementary (nonsimulation) approaches are available. I also explain how simulations can be integrated with existing spatial, environmental, historical and genetic data sets. I next describe simulation features that may be of interest to molecular ecologists, such as spatial and behavioural considerations and species' interactions, to provide guidance on how particular simulation capabilities can serve particular needs. Lastly, I discuss the prospect of simulation software in emerging challenges (climate change, biodiversity monitoring, population exploitation) and opportunities (genomics, ancient DNA), in order to emphasize that the scope of simulation-based work is expanding. I also suggest practical considerations, priorities and elements of best practice. This should accelerate the uptake of simulation approaches and firmly embed them as a versatile tool in the molecular ecologist's toolbox. © 2014 John Wiley & Sons Ltd.

Coarse-Grained Models Reveal Functional Dynamics – II. Molecular Dynamics Simulation at the Coarse-Grained Level – Theories and Biological Applications

PubMed Central

Chng, Choon-Peng; Yang, Lee-Wei

2008-01-01

Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the absence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed. PMID:19812774

Self-assembly formation of palm-based esters nano-emulsion: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Abdul Rahman, Mohd. Basyaruddin; Huan, Qiu-Yi; Tejo, Bimo A.; Basri, Mahiran; Salleh, Abu Bakar; Rahman, Raja Noor Zaliha Abdul

2009-10-01

Palm-oil esters (POEs) are unsaturated and non-ionic esters that can be prepared by enzymatic synthesis from palm oil. Their nano-emulsion properties possess great potential to act as drug carrier for transdermal drug delivery system. A ratio of 75:5:20 (water/POEs/Span20) was chosen from homogenous region in the phase diagram of our previous experimental work to undergo molecular dynamics simulation. A 15 ns molecular dynamics simulation of nano-emulsion system (water/POEs/Span20) was carried out using OPLS-AA force field. The aggregations of the oil and surfactant molecules are observed throughout the simulation. After 8 ns of simulation, the molecules start to aggregate to form one spherical micelle where the POEs molecules are surrounded by the non-ionic surfactant (Span20) molecules with an average size of 4.2 ± 0.05 nm. The size of the micelle and the ability of palm-based nano-emulsion to self-assemble suggest that this nano-emulsion can potentially use in transdermal drug delivery system.

Molecular dynamics simulation of siderite-hematite-quartz flotation with sodium oleate

NASA Astrophysics Data System (ADS)

Li, Lixia; Hao, Haiqing; Yuan, Zhitao; Liu, Jiongtian

2017-10-01

Models of sodium oleate adsorption on siderite, hematite and quartz were investigated by molecular dynamic simulation, respectively. Surface energy was calculated to confirm the cleavage plan of hematite and quartz. Both natural cleavage plane of siderite and calculated plane were used to investigate the flotation of the three minerals. Based on the molecular simulation in solution with water as medium, adsorption quantity and interaction capability of oleate ions on the three minerals indicated that siderite could be collected efficiently by sodium oleate at neutral pH. Results of flotation experiments were further demonstrated by analysis of relative concentration of carbon atoms and oxygen atoms.

Density functional theory calculation of refractive indices of liquid-forming silicon oil compounds

NASA Astrophysics Data System (ADS)

Lee, Sanghun; Park, Sung Soo; Hagelberg, Frank

2012-02-01

A combination of quantum chemical calculation and molecular dynamics simulation is applied to compute refractive indices of liquid-forming silicon oils. The densities of these species are obtained from molecular dynamics simulations based on the NPT ensemble while the molecular polarizabilities are evaluated by density functional theory. This procedure is shown to yield results well compatible with available experimental data, suggesting that it represents a robust and economic route for determining the refractive indices of liquid-forming organic complexes containing silicon.

Synthesis, Characterization, and Multimillion-Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat

DTIC Science & Technology

2013-04-01

DTRA-TR-13-23 Synthesis, Characterization, and Multimillion -Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat Approved for...reagents for the destruction of biologically active materials and a simulation of their reactions on a multimillion atom scale with quantum...explosives for destruction of chemical & biological agents. Multimillion -atom molecular dynamics simulations with quantum mechanical accuracy were

The use of molecular dynamics simulations to evaluate the DNA sequence-selectivity of G-A cross-linking PBD-duocarmycin dimers.

PubMed

Jackson, Paul J M; Rahman, Khondaker M; Thurston, David E

2017-01-01

The pyrrolobenzodiazepine (PBD) and duocarmycin families are DNA-interactive agents that covalently bond to guanine (G) and adenine (A) bases, respectively, and that have been joined together to create synthetic dimers capable of cross-linking G-G, A-A, and G-A bases. Three G-A alkylating dimers have been reported in publications to date, with defined DNA-binding sites proposed for two of them. In this study we have used molecular dynamics simulations to elucidate preferred DNA-binding sites for the three published molecular types. For the PBD-CPI dimer UTA-6026 (1), our simulations correctly predicted its favoured binding site (i.e., 5'-C(G)AATTA-3') as identified by DNA cleavage studies. However, for the PBD-CI molecule ('Compound 11', 3), we were unable to reconcile the results of our simulations with the reported preferred cross-linking sequence (5'-ATTTTCC(G)-3'). We found that the molecule is too short to span the five base pairs between the A and G bases as claimed, but should target instead a sequence such as 5'-ATTTC(G)-3' with two less base pairs between the reacting G and A residues. Our simulation results for this hybrid dimer are also in accord with the very low interstrand cross-linking and in vitro cytotoxicity activities reported for it. Although a preferred cross-linking sequence was not reported for the third hybrid dimer ('27eS', 2), our simulations predict that it should span two base pairs between covalently reacting G and A bases (e.g., 5'-GTAT(A)-3'). Copyright © 2016. Published by Elsevier Ltd.

Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design.

PubMed

Cole, Daniel J; Tirado-Rives, Julian; Jorgensen, William L

2015-05-01

Non-nucleoside inhibitors of HIV reverse transcriptase are an important component of treatment against HIV infection. Novel inhibitors are sought that increase potency against variants that contain the Tyr181Cys mutation. Molecular dynamics based free energy perturbation simulations have been run to study factors that contribute to protein-ligand binding, and the results are compared with those from previous Monte Carlo based simulations and activity data. Predictions of protein-ligand binding modes are very consistent for the two simulation methods; the accord is attributed to the use of an enhanced sampling protocol. The Tyr181Cys binding pocket supports large, hydrophobic substituents, which is in good agreement with experiment. Although some discrepancies exist between the results of the two simulation methods and experiment, free energy perturbation simulations can be used to rapidly test small molecules for gains in binding affinity. Free energy perturbation methods show promise in providing fast, reliable and accurate data that can be used to complement experiment in lead optimization projects. This article is part of a Special Issue entitled "Recent developments of molecular dynamics". Copyright © 2014 Elsevier B.V. All rights reserved.

Machine learning molecular dynamics for the simulation of infrared spectra.

PubMed

Gastegger, Michael; Behler, Jörg; Marquetand, Philipp

2017-10-01

Machine learning has emerged as an invaluable tool in many research areas. In the present work, we harness this power to predict highly accurate molecular infrared spectra with unprecedented computational efficiency. To account for vibrational anharmonic and dynamical effects - typically neglected by conventional quantum chemistry approaches - we base our machine learning strategy on ab initio molecular dynamics simulations. While these simulations are usually extremely time consuming even for small molecules, we overcome these limitations by leveraging the power of a variety of machine learning techniques, not only accelerating simulations by several orders of magnitude, but also greatly extending the size of systems that can be treated. To this end, we develop a molecular dipole moment model based on environment dependent neural network charges and combine it with the neural network potential approach of Behler and Parrinello. Contrary to the prevalent big data philosophy, we are able to obtain very accurate machine learning models for the prediction of infrared spectra based on only a few hundreds of electronic structure reference points. This is made possible through the use of molecular forces during neural network potential training and the introduction of a fully automated sampling scheme. We demonstrate the power of our machine learning approach by applying it to model the infrared spectra of a methanol molecule, n -alkanes containing up to 200 atoms and the protonated alanine tripeptide, which at the same time represents the first application of machine learning techniques to simulate the dynamics of a peptide. In all of these case studies we find an excellent agreement between the infrared spectra predicted via machine learning models and the respective theoretical and experimental spectra.

Multiscale Molecular Simulation of Solution Processing of SMDPPEH: PCBM Small-Molecule Organic Solar Cells.

PubMed

Lee, Cheng-Kuang; Pao, Chun-Wei

2016-08-17

Solution-processed small-molecule organic solar cells are a promising renewable energy source because of their low production cost, mechanical flexibility, and light weight relative to their pure inorganic counterparts. In this work, we developed a coarse-grained (CG) Gay-Berne ellipsoid molecular simulation model based on atomistic trajectories from all-atom molecular dynamics simulations of smaller system sizes to systematically study the nanomorphology of the SMDPPEH/PCBM/solvent ternary blend during solution processing, including the blade-coating process by applying external shear to the solution. With the significantly reduced overall system degrees of freedom and computational acceleration from GPU, we were able to go well beyond the limitation of conventional all-atom molecular simulations with a system size on the order of hundreds of nanometers with mesoscale molecular detail. Our simulations indicate that, similar to polymer solar cells, the optimal blending ratio in small-molecule organic solar cells must provide the highest specific interfacial area for efficient exciton dissociation, while retaining balanced hole/electron transport pathway percolation. We also reveal that blade-coating processes have a significant impact on nanomorphology. For given donor/acceptor blending ratios, applying an external shear force can effectively promote donor/acceptor phase segregation and stacking in the SMDPPEH domains. The present study demonstrated the capability of an ellipsoid-based coarse-grained model for studying the nanomorphology evolution of small-molecule organic solar cells during solution processing/blade-coating and provided links between fabrication protocols and device nanomorphologies.

MaMiCo: Transient multi-instance molecular-continuum flow simulation on supercomputers

NASA Astrophysics Data System (ADS)

Neumann, Philipp; Bian, Xin

2017-11-01

We present extensions of the macro-micro-coupling tool MaMiCo, which was designed to couple continuum fluid dynamics solvers with discrete particle dynamics. To enable local extraction of smooth flow field quantities especially on rather short time scales, sampling over an ensemble of molecular dynamics simulations is introduced. We provide details on these extensions including the transient coupling algorithm, open boundary forcing, and multi-instance sampling. Furthermore, we validate the coupling in Couette flow using different particle simulation software packages and particle models, i.e. molecular dynamics and dissipative particle dynamics. Finally, we demonstrate the parallel scalability of the molecular-continuum simulations by using up to 65 536 compute cores of the supercomputer Shaheen II located at KAUST. Program Files doi:http://dx.doi.org/10.17632/w7rgdrhb85.1 Licensing provisions: BSD 3-clause Programming language: C, C++ External routines/libraries: For compiling: SCons, MPI (optional) Subprograms used: ESPResSo, LAMMPS, ls1 mardyn, waLBerla For installation procedures of the MaMiCo interfaces, see the README files in the respective code directories located in coupling/interface/impl. Journal reference of previous version: P. Neumann, H. Flohr, R. Arora, P. Jarmatz, N. Tchipev, H.-J. Bungartz. MaMiCo: Software design for parallel molecular-continuum flow simulations, Computer Physics Communications 200: 324-335, 2016 Does the new version supersede the previous version?: Yes. The functionality of the previous version is completely retained in the new version. Nature of problem: Coupled molecular-continuum simulation for multi-resolution fluid dynamics: parts of the domain are resolved by molecular dynamics or another particle-based solver whereas large parts are covered by a mesh-based CFD solver, e.g. a lattice Boltzmann automaton. Solution method: We couple existing MD and CFD solvers via MaMiCo (macro-micro coupling tool). Data exchange and coupling algorithmics are abstracted and incorporated in MaMiCo. Once an algorithm is set up in MaMiCo, it can be used and extended, even if other solvers are used (as soon as the respective interfaces are implemented/available). Reasons for the new version: We have incorporated a new algorithm to simulate transient molecular-continuum systems and to automatically sample data over multiple MD runs that can be executed simultaneously (on, e.g., a compute cluster). MaMiCo has further been extended by an interface to incorporate boundary forcing to account for open molecular dynamics boundaries. Besides support for coupling with various MD and CFD frameworks, the new version contains a test case that allows to run molecular-continuum Couette flow simulations out-of-the-box. No external tools or simulation codes are required anymore. However, the user is free to switch from the included MD simulation package to LAMMPS. For details on how to run the transient Couette problem, see the file README in the folder coupling/tests, Remark on MaMiCo V1.1. Summary of revisions: Open boundary forcing; Multi-instance MD sampling; support for transient molecular-continuum systems Restrictions: Currently, only single-centered systems are supported. For access to the LAMMPS-based implementation of DPD boundary forcing, please contact Xin Bian, xin.bian@tum.de. Additional comments: Please see file license_mamico.txt for further details regarding distribution and advertising of this software.

Coarse-grained molecular dynamics simulations for giant protein-DNA complexes

NASA Astrophysics Data System (ADS)

Takada, Shoji

Biomolecules are highly hierarchic and intrinsically flexible. Thus, computational modeling calls for multi-scale methodologies. We have been developing a coarse-grained biomolecular model where on-average 10-20 atoms are grouped into one coarse-grained (CG) particle. Interactions among CG particles are tuned based on atomistic interactions and the fluctuation matching algorithm. CG molecular dynamics methods enable us to simulate much longer time scale motions of much larger molecular systems than fully atomistic models. After broad sampling of structures with CG models, we can easily reconstruct atomistic models, from which one can continue conventional molecular dynamics simulations if desired. Here, we describe our CG modeling methodology for protein-DNA complexes, together with various biological applications, such as the DNA duplication initiation complex, model chromatins, and transcription factor dynamics on chromatin-like environment.

Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

NASA Astrophysics Data System (ADS)

Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

2015-02-01

The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

High-pressure/high-temperature polymorphs of energetic materials by first-principles simulations

NASA Astrophysics Data System (ADS)

Le, Nam; Schweigert, Igor

2017-06-01

Energetic molecular crystals exhibit complex phase diagrams that include solid-solid phase transitions, melting, and decomposition. Sorescu and Rice have recently demonstrated that first-principles molecular dynamics (MD) simulations based on dispersion-corrected density functional theory (DFT) can capture the α to γ phase transition in hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) on time scales of several picoseconds. Motivated by their work, we are using DFT-based MD to model the relative stability of solid phases in several molecular crystals. In this presentation, we report simulations of pentaerythritol tetranitrate (PETN) and 2,4,6-trinitrotoluene (TNT) under high pressures and temperatures and compare them with experimentally observed polymorphs. This work was supported by the U.S. Naval Research Laboratory via the National Research Council and by the Office of Naval Research through the U.S. Naval Research Laboratory.

Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations

PubMed Central

Tan, Cheng; Takada, Shoji

2017-01-01

While nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements. PMID:29194442

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

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

Reconstructing the regulatory network controlling commitment and sporulation in Physarum polycephalum based on hierarchical Petri Net modelling and simulation.

PubMed

Marwan, Wolfgang; Sujatha, Arumugam; Starostzik, Christine

2005-10-21

We reconstruct the regulatory network controlling commitment and sporulation of Physarum polycephalum from experimental results using a hierarchical Petri Net-based modelling and simulation framework. The stochastic Petri Net consistently describes the structure and simulates the dynamics of the molecular network as analysed by genetic, biochemical and physiological experiments within a single coherent model. The Petri Net then is extended to simulate time-resolved somatic complementation experiments performed by mixing the cytoplasms of mutants altered in the sporulation response, to systematically explore the network structure and to probe its dynamics. This reverse engineering approach presumably can be employed to explore other molecular or genetic signalling systems where the activity of genes or their products can be experimentally controlled in a time-resolved manner.

Evaporation kinetics of Mg2SiO4 crystals and melts from molecular dynamics simulations

NASA Technical Reports Server (NTRS)

Kubicki, J. D.; Stolper, E. M.

1993-01-01

Computer simulations based on the molecular dynamics (MD) technique were used to study the mechanisms and kinetics of free evaporation from crystalline and molten forsterite (i.e., Mg2SiO4) on an atomic level. The interatomic potential employed for these simulations reproduces the energetics of bonding in forsterite and in gas-phase MgO and SiO2 reasonably accurately. Results of the simulation include predicted evaporation rates, diffusion rates, and reaction mechanisms for Mg2SiO4(s or l) yields 2Mg(g) + 20(g) + SiO2(g).

A Molecular Dynamics-Quantum Mechanics Theoretical Study of DNA-Mediated Charge Transport in Hydrated Ionic Liquids.

PubMed

Meng, Zhenyu; Kubar, Tomas; Mu, Yuguang; Shao, Fangwei

2018-05-08

Charge transport (CT) through biomolecules is of high significance in the research fields of biology, nanotechnology, and molecular devices. Inspired by our previous work that showed the binding of ionic liquid (IL) facilitated charge transport in duplex DNA, in silico simulation is a useful means to understand the microscopic mechanism of the facilitation phenomenon. Here molecular dynamics simulations (MD) of duplex DNA in water and hydrated ionic liquids were employed to explore the helical parameters. Principal component analysis was further applied to capture the subtle conformational changes of helical DNA upon different environmental impacts. Sequentially, CT rates were calculated by a QM/MM simulation of the flickering resonance model based upon MD trajectories. Herein, MD simulation illustrated that the binding of ionic liquids can restrain dynamic conformation and lower the on-site energy of the DNA base. Confined movement among the adjacent base pairs was highly related to the increase of electronic coupling among base pairs, which may lead DNA to a CT facilitated state. Sequentially combining MD and QM/MM analysis, the rational correlations among the binding modes, the conformational changes, and CT rates illustrated the facilitation effects from hydrated IL on DNA CT and supported a conformational-gating mechanism.

Dissipative particle dynamics (DPD) simulations with fragment molecular orbital (FMO) based effective parameters for 1-Palmitoyl-2-oleoyl phosphatidyl choline (POPC) membrane

NASA Astrophysics Data System (ADS)

Doi, Hideo; Okuwaki, Koji; Mochizuki, Yuji; Ozawa, Taku; Yasuoka, Kenji

2017-09-01

In dissipative particle dynamics (DPD) simulations, it is necessary to use the so-called χ parameter set that express the effective interactions between particles. Recently, we have developed a new scheme to evaluate the χ parameters in a non-empirical way through a series of fragment molecular orbital (FMO) calculations. As a challenging test, we have performed the DPD simulations using the FMO-based χ parameters for a mixture of 1-Palmitoyl-2-oleoyl phosphatidyl choline (POPC) and water. The structures of both membrane and vesicle were formed successfully. The calculated structural parameters of membrane were in good agreement with experimental results.

Computational Nanomechanics of Carbon Nanotubes and Composites

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Wei, Chenyu; Cho, Kyeongjae; Biegel, Bryan (Technical Monitor)

2002-01-01

Nanomechanics of individual carbon and boron-nitride nanotubes and their application as reinforcing fibers in polymer composites has been reviewed with interplay of theoretical modeling, computer simulations and experimental observations. The emphasis in this work is on elucidating the multi-length scales of the problems involved, and of different simulation techniques that are needed to address specific characteristics of individual nanotubes and nanotube polymer-matrix interfaces. Classical molecular dynamics simulations are shown to be sufficient to describe the generic behavior such as strength and stiffness modulus but are inadequate to describe elastic limit and nature of plastic buckling at large strength. Quantum molecular dynamics simulations are shown to bring out explicit atomic nature dependent behavior of these nanoscale materials objects that are not accessible either via continuum mechanics based descriptions or through classical molecular dynamics based simulations. As examples, we discus local plastic collapse of carbon nanotubes under axial compression and anisotropic plastic buckling of boron-nitride nanotubes. Dependence of the yield strain on the strain rate is addressed through temperature dependent simulations, a transition-state-theory based model of the strain as a function of strain rate and simulation temperature is presented, and in all cases extensive comparisons are made with experimental observations. Mechanical properties of nanotube-polymer composite materials are simulated with diverse nanotube-polymer interface structures (with van der Waals interaction). The atomistic mechanisms of the interface toughening for optimal load transfer through recycling, high-thermal expansion and diffusion coefficient composite formation above glass transition temperature, and enhancement of Young's modulus on addition of nanotubes to polymer are discussed and compared with experimental observations.

Coulomb interactions in charged fluids.

PubMed

Vernizzi, Graziano; Guerrero-García, Guillermo Iván; de la Cruz, Monica Olvera

2011-07-01

The use of Ewald summation schemes for calculating long-range Coulomb interactions, originally applied to ionic crystalline solids, is a very common practice in molecular simulations of charged fluids at present. Such a choice imposes an artificial periodicity which is generally absent in the liquid state. In this paper we propose a simple analytical O(N(2)) method which is based on Gauss's law for computing exactly the Coulomb interaction between charged particles in a simulation box, when it is averaged over all possible orientations of a surrounding infinite lattice. This method mitigates the periodicity typical of crystalline systems and it is suitable for numerical studies of ionic liquids, charged molecular fluids, and colloidal systems with Monte Carlo and molecular dynamics simulations.

Smoldyn: particle-based simulation with rule-based modeling, improved molecular interaction and a library interface.

PubMed

Andrews, Steven S

2017-03-01

Smoldyn is a spatial and stochastic biochemical simulator. It treats each molecule of interest as an individual particle in continuous space, simulating molecular diffusion, molecule-membrane interactions and chemical reactions, all with good accuracy. This article presents several new features. Smoldyn now supports two types of rule-based modeling. These are a wildcard method, which is very convenient, and the BioNetGen package with extensions for spatial simulation, which is better for complicated models. Smoldyn also includes new algorithms for simulating the diffusion of surface-bound molecules and molecules with excluded volume. Both are exact in the limit of short time steps and reasonably good with longer steps. In addition, Smoldyn supports single-molecule tracking simulations. Finally, the Smoldyn source code can be accessed through a C/C ++ language library interface. Smoldyn software, documentation, code, and examples are at http://www.smoldyn.org . steven.s.andrews@gmail.com. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Analysis of Factors Influencing Hydration Site Prediction Based on Molecular Dynamics Simulations

PubMed Central

2015-01-01

Water contributes significantly to the binding of small molecules to proteins in biochemical systems. Molecular dynamics (MD) simulation based programs such as WaterMap and WATsite have been used to probe the locations and thermodynamic properties of hydration sites at the surface or in the binding site of proteins generating important information for structure-based drug design. However, questions associated with the influence of the simulation protocol on hydration site analysis remain. In this study, we use WATsite to investigate the influence of factors such as simulation length and variations in initial protein conformations on hydration site prediction. We find that 4 ns MD simulation is appropriate to obtain a reliable prediction of the locations and thermodynamic properties of hydration sites. In addition, hydration site prediction can be largely affected by the initial protein conformations used for MD simulations. Here, we provide a first quantification of this effect and further indicate that similar conformations of binding site residues (RMSD < 0.5 Å) are required to obtain consistent hydration site predictions. PMID:25252619

Ab initio molecular simulations with numeric atom-centered orbitals

NASA Astrophysics Data System (ADS)

Blum, Volker; Gehrke, Ralf; Hanke, Felix; Havu, Paula; Havu, Ville; Ren, Xinguo; Reuter, Karsten; Scheffler, Matthias

2009-11-01

We describe a complete set of algorithms for ab initio molecular simulations based on numerically tabulated atom-centered orbitals (NAOs) to capture a wide range of molecular and materials properties from quantum-mechanical first principles. The full algorithmic framework described here is embodied in the Fritz Haber Institute "ab initio molecular simulations" (FHI-aims) computer program package. Its comprehensive description should be relevant to any other first-principles implementation based on NAOs. The focus here is on density-functional theory (DFT) in the local and semilocal (generalized gradient) approximations, but an extension to hybrid functionals, Hartree-Fock theory, and MP2/GW electron self-energies for total energies and excited states is possible within the same underlying algorithms. An all-electron/full-potential treatment that is both computationally efficient and accurate is achieved for periodic and cluster geometries on equal footing, including relaxation and ab initio molecular dynamics. We demonstrate the construction of transferable, hierarchical basis sets, allowing the calculation to range from qualitative tight-binding like accuracy to meV-level total energy convergence with the basis set. Since all basis functions are strictly localized, the otherwise computationally dominant grid-based operations scale as O(N) with system size N. Together with a scalar-relativistic treatment, the basis sets provide access to all elements from light to heavy. Both low-communication parallelization of all real-space grid based algorithms and a ScaLapack-based, customized handling of the linear algebra for all matrix operations are possible, guaranteeing efficient scaling (CPU time and memory) up to massively parallel computer systems with thousands of CPUs.

Computational Nanotechnology of Molecular Materials, Electronics, and Actuators with Carbon Nanotubes and Fullerenes

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Menon, Madhu; Cho, Kyeongjae; Biegel, Bryan (Technical Monitor)

2001-01-01

The role of computational nanotechnology in developing next generation of multifunctional materials, molecular scale electronic and computing devices, sensors, actuators, and machines is described through a brief review of enabling computational techniques and few recent examples derived from computer simulations of carbon nanotube based molecular nanotechnology.

Structure refinement of membrane proteins via molecular dynamics simulations.

PubMed

Dutagaci, Bercem; Heo, Lim; Feig, Michael

2018-07-01

A refinement protocol based on physics-based techniques established for water soluble proteins is tested for membrane protein structures. Initial structures were generated by homology modeling and sampled via molecular dynamics simulations in explicit lipid bilayer and aqueous solvent systems. Snapshots from the simulations were selected based on scoring with either knowledge-based or implicit membrane-based scoring functions and averaged to obtain refined models. The protocol resulted in consistent and significant refinement of the membrane protein structures similar to the performance of refinement methods for soluble proteins. Refinement success was similar between sampling in the presence of lipid bilayers and aqueous solvent but the presence of lipid bilayers may benefit the improvement of lipid-facing residues. Scoring with knowledge-based functions (DFIRE and RWplus) was found to be as good as scoring using implicit membrane-based scoring functions suggesting that differences in internal packing is more important than orientations relative to the membrane during the refinement of membrane protein homology models. © 2018 Wiley Periodicals, Inc.

MOlecular MAterials Property Prediction Package (MOMAP) 1.0: a software package for predicting the luminescent properties and mobility of organic functional materials

NASA Astrophysics Data System (ADS)

Niu, Yingli; Li, Wenqiang; Peng, Qian; Geng, Hua; Yi, Yuanping; Wang, Linjun; Nan, Guangjun; Wang, Dong; Shuai, Zhigang

2018-04-01

MOlecular MAterials Property Prediction Package (MOMAP) is a software toolkit for molecular materials property prediction. It focuses on luminescent properties and charge mobility properties. This article contains a brief descriptive introduction of key features, theoretical models and algorithms of the software, together with examples that illustrate the performance. First, we present the theoretical models and algorithms for molecular luminescent properties calculation, which includes the excited-state radiative/non-radiative decay rate constant and the optical spectra. Then, a multi-scale simulation approach and its algorithm for the molecular charge mobility are described. This approach is based on hopping model and combines with Kinetic Monte Carlo and molecular dynamics simulations, and it is especially applicable for describing a large category of organic semiconductors, whose inter-molecular electronic coupling is much smaller than intra-molecular charge reorganisation energy.

ReaxFF based molecular dynamics simulations of ignition front propagation in hydrocarbon/oxygen mixtures under high temperature and pressure conditions.

PubMed

Ashraf, Chowdhury; Jain, Abhishek; Xuan, Yuan; van Duin, Adri C T

2017-02-15

In this paper, we present the first atomistic-scale based method for calculating ignition front propagation speed and hypothesize that this quantity is related to laminar flame speed. This method is based on atomistic-level molecular dynamics (MD) simulations with the ReaxFF reactive force field. Results reported in this study are for supercritical (P = 55 MPa and T u = 1800 K) combustion of hydrocarbons as elevated pressure and temperature are required to accelerate the dynamics for reactive MD simulations. These simulations are performed for different types of hydrocarbons, including alkyne, alkane, and aromatic, and are able to successfully reproduce the experimental trend of reactivity of these hydrocarbons. Moreover, our results indicate that the ignition front propagation speed under supercritical conditions has a strong dependence on equivalence ratio, similar to experimentally measured flame speeds at lower temperatures and pressures which supports our hypothesis that ignition front speed is a related quantity to laminar flame speed. In addition, comparisons between results obtained from ReaxFF simulation and continuum simulations performed under similar conditions show good qualitative, and reasonable quantitative agreement. This demonstrates that ReaxFF based MD-simulations are a promising tool to study flame speed/ignition front speed in supercritical hydrocarbon combustion.

Characteristics of the mixing volume model with the interactions among spatially distributed particles for Lagrangian simulations of turbulent mixing

NASA Astrophysics Data System (ADS)

Watanabe, Tomoaki; Nagata, Koji

2016-11-01

The mixing volume model (MVM), which is a mixing model for molecular diffusion in Lagrangian simulations of turbulent mixing problems, is proposed based on the interactions among spatially distributed particles in a finite volume. The mixing timescale in the MVM is derived by comparison between the model and the subgrid scale scalar variance equation. A-priori test of the MVM is conducted based on the direct numerical simulations of planar jets. The MVM is shown to predict well the mean effects of the molecular diffusion under various conditions. However, a predicted value of the molecular diffusion term is positively correlated to the exact value in the DNS only when the number of the mixing particles is larger than two. Furthermore, the MVM is tested in the hybrid implicit large-eddy-simulation/Lagrangian-particle-simulation (ILES/LPS). The ILES/LPS with the present mixing model predicts well the decay of the scalar variance in planar jets. This work was supported by JSPS KAKENHI Nos. 25289030 and 16K18013. The numerical simulations presented in this manuscript were carried out on the high performance computing system (NEC SX-ACE) in the Japan Agency for Marine-Earth Science and Technology.

Subtle Monte Carlo Updates in Dense Molecular Systems.

PubMed

Bottaro, Sandro; Boomsma, Wouter; E Johansson, Kristoffer; Andreetta, Christian; Hamelryck, Thomas; Ferkinghoff-Borg, Jesper

2012-02-14

Although Markov chain Monte Carlo (MC) simulation is a potentially powerful approach for exploring conformational space, it has been unable to compete with molecular dynamics (MD) in the analysis of high density structural states, such as the native state of globular proteins. Here, we introduce a kinetic algorithm, CRISP, that greatly enhances the sampling efficiency in all-atom MC simulations of dense systems. The algorithm is based on an exact analytical solution to the classic chain-closure problem, making it possible to express the interdependencies among degrees of freedom in the molecule as correlations in a multivariate Gaussian distribution. We demonstrate that our method reproduces structural variation in proteins with greater efficiency than current state-of-the-art Monte Carlo methods and has real-time simulation performance on par with molecular dynamics simulations. The presented results suggest our method as a valuable tool in the study of molecules in atomic detail, offering a potential alternative to molecular dynamics for probing long time-scale conformational transitions.

SpectraPlot.com: Integrated spectroscopic modeling of atomic and molecular gases

NASA Astrophysics Data System (ADS)

Goldenstein, Christopher S.; Miller, Victor A.; Mitchell Spearrin, R.; Strand, Christopher L.

2017-10-01

SpectraPlot is a web-based application for simulating spectra of atomic and molecular gases. At the time this manuscript was written, SpectraPlot consisted of four primary tools for calculating: (1) atomic and molecular absorption spectra, (2) atomic and molecular emission spectra, (3) transition linestrengths, and (4) blackbody emission spectra. These tools currently employ the NIST ASD, HITRAN2012, and HITEMP2010 databases to perform line-by-line simulations of spectra. SpectraPlot employs a modular, integrated architecture, enabling multiple simulations across multiple databases and/or thermodynamic conditions to be visualized in an interactive plot window. The primary objective of this paper is to describe the architecture and spectroscopic models employed by SpectraPlot in order to provide its users with the knowledge required to understand the capabilities and limitations of simulations performed using SpectraPlot. Further, this manuscript discusses the accuracy of several underlying approximations used to decrease computational time, in particular, the use of far-wing cutoff criteria.

Structure and dynamics of acetate anion-based ionic liquids from molecular dynamics study

NASA Astrophysics Data System (ADS)

Chandran, Aneesh; Prakash, Karthigeyan; Senapati, Sanjib

2010-08-01

Acetate anion-based ionic liquids (ILs) have found wide range of applications. The microstructure and dynamics of this IL family have not been clearly understood yet. We report molecular dynamics simulation results of three acetate anion-based ionic liquids that encompass the most common IL cations. Simulations are performed based on a set of proposed force field parameters for IL acetate anion which can be combined with existing parameters for IL cations to simulate large variety of ILs. The computed liquid density and IR spectral data for [BMIM][Ac] are found to match very well with available experimental results. The strong amino-group-associated interactions in [TMG][Ac] are seen to bring about higher cohesive energy density, stronger ion packing, and more restricted translational and rotational mobilities of the constituent ions. The IL anions are found to track the cation movements in all systems, implying that ions in ILs travel in pairs or clusters.

MoleculaRnetworks: an integrated graph theoretic and data mining tool to explore solvent organization in molecular simulation.

PubMed

Mooney, Barbara Logan; Corrales, L René; Clark, Aurora E

2012-03-30

This work discusses scripts for processing molecular simulations data written using the software package R: A Language and Environment for Statistical Computing. These scripts, named moleculaRnetworks, are intended for the geometric and solvent network analysis of aqueous solutes and can be extended to other H-bonded solvents. New algorithms, several of which are based on graph theory, that interrogate the solvent environment about a solute are presented and described. This includes a novel method for identifying the geometric shape adopted by the solvent in the immediate vicinity of the solute and an exploratory approach for describing H-bonding, both based on the PageRank algorithm of Google search fame. The moleculaRnetworks codes include a preprocessor, which distills simulation trajectories into physicochemical data arrays, and an interactive analysis script that enables statistical, trend, and correlation analysis, and other data mining. The goal of these scripts is to increase access to the wealth of structural and dynamical information that can be obtained from molecular simulations. Copyright © 2012 Wiley Periodicals, Inc.

Molecular-Level Simulations of Shock Generation and Propagation in Soda-Lime Glass

DTIC Science & Technology

2012-08-01

Molecular-Level Simulations of Shock Generation and Propagation in Soda-Lime Glass M. Grujicic, W.C. Bell, B. Pandurangan, B.A. Cheeseman, C ...transparent structures with thickness approaching several inches; (b) relatively low material and manufacturing costs; and ( c ) compositional modifications... c ) models based on explicit crack representation (Ref 15, 16). Since a M. Grujicic, W.C. Bell, and B. Pandurangan, Department of Mec- hanical

Smoothed-particle hydrodynamics and nonequilibrium molecular dynamics

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

Hoover, W. G.; Hoover, C. G.

1993-08-01

Gingold, Lucy, and Monaghan invented a grid-free version of continuum mechanics ``smoothed-particle hydrodynamics,`` in 1977. It is a likely contributor to ``hybrid`` simulations combining atomistic and continuum simulations. We describe applications of this particle-based continuum technique from the closely-related standpoint of nonequilibrium molecular dynamics. We compare chaotic Lyapunov spectra for atomistic solids and fluids with those which characterize a two-dimensional smoothed-particle fluid system.

Simulational nanoengineering: Molecular dynamics implementation of an atomistic Stirling engine.

PubMed

Rapaport, D C

2009-04-01

A nanoscale-sized Stirling engine with an atomistic working fluid has been modeled using molecular dynamics simulation. The design includes heat exchangers based on thermostats, pistons attached to a flywheel under load, and a regenerator. Key aspects of the behavior, including the time-dependent flows, are described. The model is shown to be capable of stable operation while producing net work at a moderate level of efficiency.

Mechanical features of various silkworm crystalline considering hydration effect via molecular dynamics simulations.

PubMed

Kim, Yoonjung; Lee, Myeongsang; Choi, Hyunsung; Baek, Inchul; Kim, Jae In; Na, Sungsoo

2018-04-01

Silk materials are receiving significant attention as base materials for various functional nanomaterials and nanodevices, due to its exceptionally high mechanical properties, biocompatibility, and degradable characteristics. Although crystalline silk regions are composed of various repetitive motifs with differing amino acid sequences, how the effect of humidity works differently on each of the motifs and their structural characteristics remains unclear. We report molecular dynamics (MD) simulations on various silkworm fibroins composed of major motifs (i.e. (GAGAGS) n , (GAGAGA) n , and (GAGAGY) n ) at varying degrees of hydration, and reveal how each major motifs of silk fibroins change at each degrees of hydration using MD simulations and their structural properties in mechanical perspective via steered molecular dynamics simulations. Our results explain what effects humidity can have on nanoscale materials and devices consisting of crystalline silk materials.

OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation.

PubMed

Eastman, Peter; Friedrichs, Mark S; Chodera, John D; Radmer, Randall J; Bruns, Christopher M; Ku, Joy P; Beauchamp, Kyle A; Lane, Thomas J; Wang, Lee-Ping; Shukla, Diwakar; Tye, Tony; Houston, Mike; Stich, Timo; Klein, Christoph; Shirts, Michael R; Pande, Vijay S

2013-01-08

OpenMM is a software toolkit for performing molecular simulations on a range of high performance computing architectures. It is based on a layered architecture: the lower layers function as a reusable library that can be invoked by any application, while the upper layers form a complete environment for running molecular simulations. The library API hides all hardware-specific dependencies and optimizations from the users and developers of simulation programs: they can be run without modification on any hardware on which the API has been implemented. The current implementations of OpenMM include support for graphics processing units using the OpenCL and CUDA frameworks. In addition, OpenMM was designed to be extensible, so new hardware architectures can be accommodated and new functionality (e.g., energy terms and integrators) can be easily added.

OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation

PubMed Central

Eastman, Peter; Friedrichs, Mark S.; Chodera, John D.; Radmer, Randall J.; Bruns, Christopher M.; Ku, Joy P.; Beauchamp, Kyle A.; Lane, Thomas J.; Wang, Lee-Ping; Shukla, Diwakar; Tye, Tony; Houston, Mike; Stich, Timo; Klein, Christoph; Shirts, Michael R.; Pande, Vijay S.

2012-01-01

OpenMM is a software toolkit for performing molecular simulations on a range of high performance computing architectures. It is based on a layered architecture: the lower layers function as a reusable library that can be invoked by any application, while the upper layers form a complete environment for running molecular simulations. The library API hides all hardware-specific dependencies and optimizations from the users and developers of simulation programs: they can be run without modification on any hardware on which the API has been implemented. The current implementations of OpenMM include support for graphics processing units using the OpenCL and CUDA frameworks. In addition, OpenMM was designed to be extensible, so new hardware architectures can be accommodated and new functionality (e.g., energy terms and integrators) can be easily added. PMID:23316124

Recursive Factorization of the Inverse Overlap Matrix in Linear-Scaling Quantum Molecular Dynamics Simulations.

PubMed

Negre, Christian F A; Mniszewski, Susan M; Cawkwell, Marc J; Bock, Nicolas; Wall, Michael E; Niklasson, Anders M N

2016-07-12

We present a reduced complexity algorithm to compute the inverse overlap factors required to solve the generalized eigenvalue problem in a quantum-based molecular dynamics (MD) simulation. Our method is based on the recursive, iterative refinement of an initial guess of Z (inverse square root of the overlap matrix S). The initial guess of Z is obtained beforehand by using either an approximate divide-and-conquer technique or dynamical methods, propagated within an extended Lagrangian dynamics from previous MD time steps. With this formulation, we achieve long-term stability and energy conservation even under the incomplete, approximate, iterative refinement of Z. Linear-scaling performance is obtained using numerically thresholded sparse matrix algebra based on the ELLPACK-R sparse matrix data format, which also enables efficient shared-memory parallelization. As we show in this article using self-consistent density-functional-based tight-binding MD, our approach is faster than conventional methods based on the diagonalization of overlap matrix S for systems as small as a few hundred atoms, substantially accelerating quantum-based simulations even for molecular structures of intermediate size. For a 4158-atom water-solvated polyalanine system, we find an average speedup factor of 122 for the computation of Z in each MD step.

Recursive Factorization of the Inverse Overlap Matrix in Linear Scaling Quantum Molecular Dynamics Simulations

DOE PAGES

Negre, Christian F. A; Mniszewski, Susan M.; Cawkwell, Marc Jon; ...

2016-06-06

We present a reduced complexity algorithm to compute the inverse overlap factors required to solve the generalized eigenvalue problem in a quantum-based molecular dynamics (MD) simulation. Our method is based on the recursive iterative re nement of an initial guess Z of the inverse overlap matrix S. The initial guess of Z is obtained beforehand either by using an approximate divide and conquer technique or dynamically, propagated within an extended Lagrangian dynamics from previous MD time steps. With this formulation, we achieve long-term stability and energy conservation even under incomplete approximate iterative re nement of Z. Linear scaling performance ismore » obtained using numerically thresholded sparse matrix algebra based on the ELLPACK-R sparse matrix data format, which also enables e cient shared memory parallelization. As we show in this article using selfconsistent density functional based tight-binding MD, our approach is faster than conventional methods based on the direct diagonalization of the overlap matrix S for systems as small as a few hundred atoms, substantially accelerating quantum-based simulations even for molecular structures of intermediate size. For a 4,158 atom water-solvated polyalanine system we nd an average speedup factor of 122 for the computation of Z in each MD step.« less

Achieving Rigorous Accelerated Conformational Sampling in Explicit Solvent.

PubMed

Doshi, Urmi; Hamelberg, Donald

2014-04-03

Molecular dynamics simulations can provide valuable atomistic insights into biomolecular function. However, the accuracy of molecular simulations on general-purpose computers depends on the time scale of the events of interest. Advanced simulation methods, such as accelerated molecular dynamics, have shown tremendous promise in sampling the conformational dynamics of biomolecules, where standard molecular dynamics simulations are nonergodic. Here we present a sampling method based on accelerated molecular dynamics in which rotatable dihedral angles and nonbonded interactions are boosted separately. This method (RaMD-db) is a different implementation of the dual-boost accelerated molecular dynamics, introduced earlier. The advantage is that this method speeds up sampling of the conformational space of biomolecules in explicit solvent, as the degrees of freedom most relevant for conformational transitions are accelerated. We tested RaMD-db on one of the most difficult sampling problems - protein folding. Starting from fully extended polypeptide chains, two fast folding α-helical proteins (Trpcage and the double mutant of C-terminal fragment of Villin headpiece) and a designed β-hairpin (Chignolin) were completely folded to their native structures in very short simulation time. Multiple folding/unfolding transitions could be observed in a single trajectory. Our results show that RaMD-db is a promisingly fast and efficient sampling method for conformational transitions in explicit solvent. RaMD-db thus opens new avenues for understanding biomolecular self-assembly and functional dynamics occurring on long time and length scales.

ProbeZT: Simulation of transport coefficients of molecular electronic junctions under environmental effects using Büttiker's probes

NASA Astrophysics Data System (ADS)

Korol, Roman; Kilgour, Michael; Segal, Dvira

2018-03-01

We present our in-house quantum transport package, ProbeZT. This program provides linear response coefficients: electrical and electronic thermal conductances, as well as the thermopower of molecular junctions in which electrons interact with the surrounding thermal environment. Calculations are performed based on the Büttiker probe method, which introduces decoherence, energy exchange and dissipation effects phenomenologically using virtual electrode terminals called probes. The program can realize different types of probes, each introducing various environmental effects, including elastic and inelastic scattering of electrons. The molecular system is described by an arbitrary tight-binding Hamiltonian, allowing the study of different geometries beyond simple one-dimensional wires. Applications of the program to study the thermoelectric performance of molecular junctions are illustrated. The program also has a built-in functionality to simulate electron transport in double-stranded DNA molecules based on a tight-binding (ladder) description of the junction.

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.

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

NASA Astrophysics Data System (ADS)

Cheng, Shengfeng; Wen, Chengyuan; Egorov, Sergei

2015-03-01

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

A network of molecular switches controls the activation of the two-component response regulator NtrC

NASA Astrophysics Data System (ADS)

Vanatta, Dan K.; Shukla, Diwakar; Lawrenz, Morgan; Pande, Vijay S.

2015-06-01

Recent successes in simulating protein structure and folding dynamics have demonstrated the power of molecular dynamics to predict the long timescale behaviour of proteins. Here, we extend and improve these methods to predict molecular switches that characterize conformational change pathways between the active and inactive state of nitrogen regulatory protein C (NtrC). By employing unbiased Markov state model-based molecular dynamics simulations, we construct a dynamic picture of the activation pathways of this key bacterial signalling protein that is consistent with experimental observations and predicts new mutants that could be used for validation of the mechanism. Moreover, these results suggest a novel mechanistic paradigm for conformational switching.

Simulating Energy Relaxation in Pump-Probe Vibrational Spectroscopy of Hydrogen-Bonded Liquids.

PubMed

Dettori, Riccardo; Ceriotti, Michele; Hunger, Johannes; Melis, Claudio; Colombo, Luciano; Donadio, Davide

2017-03-14

We introduce a nonequilibrium molecular dynamics simulation approach, based on the generalized Langevin equation, to study vibrational energy relaxation in pump-probe spectroscopy. A colored noise thermostat is used to selectively excite a set of vibrational modes, leaving the other modes nearly unperturbed, to mimic the effect of a monochromatic laser pump. Energy relaxation is probed by analyzing the evolution of the system after excitation in the microcanonical ensemble, thus providing direct information about the energy redistribution paths at the molecular level and their time scale. The method is applied to hydrogen-bonded molecular liquids, specifically deuterated methanol and water, providing a robust picture of energy relaxation at the molecular scale.

Combining configurational energies and forces for molecular force field optimization

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

Vlcek, Lukas; Sun, Weiwei; Kent, Paul R. C.

While quantum chemical simulations have been increasingly used as an invaluable source of information for atomistic model development, the high computational expenses typically associated with these techniques often limit thorough sampling of the systems of interest. It is therefore of great practical importance to use all available information as efficiently as possible, and in a way that allows for consistent addition of constraints that may be provided by macroscopic experiments. We propose a simple approach that combines information from configurational energies and forces generated in a molecular dynamics simulation to increase the effective number of samples. Subsequently, this information ismore » used to optimize a molecular force field by minimizing the statistical distance similarity metric. We also illustrate the methodology on an example of a trajectory of configurations generated in equilibrium molecular dynamics simulations of argon and water and compare the results with those based on the force matching method.« less

Combining configurational energies and forces for molecular force field optimization

DOE PAGES

Vlcek, Lukas; Sun, Weiwei; Kent, Paul R. C.

2017-07-21

While quantum chemical simulations have been increasingly used as an invaluable source of information for atomistic model development, the high computational expenses typically associated with these techniques often limit thorough sampling of the systems of interest. It is therefore of great practical importance to use all available information as efficiently as possible, and in a way that allows for consistent addition of constraints that may be provided by macroscopic experiments. We propose a simple approach that combines information from configurational energies and forces generated in a molecular dynamics simulation to increase the effective number of samples. Subsequently, this information ismore » used to optimize a molecular force field by minimizing the statistical distance similarity metric. We also illustrate the methodology on an example of a trajectory of configurations generated in equilibrium molecular dynamics simulations of argon and water and compare the results with those based on the force matching method.« 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.

Faunus: An object oriented framework for molecular simulation

PubMed Central

Lund, Mikael; Trulsson, Martin; Persson, Björn

2008-01-01

Background We present a C++ class library for Monte Carlo simulation of molecular systems, including proteins in solution. The design is generic and highly modular, enabling multiple developers to easily implement additional features. The statistical mechanical methods are documented by extensive use of code comments that – subsequently – are collected to automatically build a web-based manual. Results We show how an object oriented design can be used to create an intuitively appealing coding framework for molecular simulation. This is exemplified in a minimalistic C++ program that can calculate protein protonation states. We further discuss performance issues related to high level coding abstraction. Conclusion C++ and the Standard Template Library (STL) provide a high-performance platform for generic molecular modeling. Automatic generation of code documentation from inline comments has proven particularly useful in that no separate manual needs to be maintained. PMID:18241331

Cosolvent-Based Molecular Dynamics for Ensemble Docking: Practical Method for Generating Druggable Protein Conformations.

PubMed

Uehara, Shota; Tanaka, Shigenori

2017-04-24

Protein flexibility is a major hurdle in current structure-based virtual screening (VS). In spite of the recent advances in high-performance computing, protein-ligand docking methods still demand tremendous computational cost to take into account the full degree of protein flexibility. In this context, ensemble docking has proven its utility and efficiency for VS studies, but it still needs a rational and efficient method to select and/or generate multiple protein conformations. Molecular dynamics (MD) simulations are useful to produce distinct protein conformations without abundant experimental structures. In this study, we present a novel strategy that makes use of cosolvent-based molecular dynamics (CMD) simulations for ensemble docking. By mixing small organic molecules into a solvent, CMD can stimulate dynamic protein motions and induce partial conformational changes of binding pocket residues appropriate for the binding of diverse ligands. The present method has been applied to six diverse target proteins and assessed by VS experiments using many actives and decoys of DEKOIS 2.0. The simulation results have revealed that the CMD is beneficial for ensemble docking. Utilizing cosolvent simulation allows the generation of druggable protein conformations, improving the VS performance compared with the use of a single experimental structure or ensemble docking by standard MD with pure water as the solvent.

Consistent View of Protein Fluctuations from All-Atom Molecular Dynamics and Coarse-Grained Dynamics with Knowledge-Based Force-Field.

PubMed

Jamroz, Michal; Orozco, Modesto; Kolinski, Andrzej; Kmiecik, Sebastian

2013-01-08

It is widely recognized that atomistic Molecular Dynamics (MD), a classical simulation method, captures the essential physics of protein dynamics. That idea is supported by a theoretical study showing that various MD force-fields provide a consensus picture of protein fluctuations in aqueous solution [Rueda, M. et al. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 796-801]. However, atomistic MD cannot be applied to most biologically relevant processes due to its limitation to relatively short time scales. Much longer time scales can be accessed by properly designed coarse-grained models. We demonstrate that the aforementioned consensus view of protein dynamics from short (nanosecond) time scale MD simulations is fairly consistent with the dynamics of the coarse-grained protein model - the CABS model. The CABS model employs stochastic dynamics (a Monte Carlo method) and a knowledge-based force-field, which is not biased toward the native structure of a simulated protein. Since CABS-based dynamics allows for the simulation of entire folding (or multiple folding events) in a single run, integration of the CABS approach with all-atom MD promises a convenient (and computationally feasible) means for the long-time multiscale molecular modeling of protein systems with atomistic resolution.

Designing of phenol-based β-carbonic anhydrase1 inhibitors through QSAR, molecular docking, and MD simulation approach.

PubMed

Ahamad, Shahzaib; Hassan, Md Imtaiyaz; Dwivedi, Neeraja

2018-05-01

Tuberculosis (Tb) is an airborne infectious disease caused by Mycobacterium tuberculosis. Beta-carbonic anhydrase 1 ( β-CA1 ) has emerged as one of the potential targets for new antitubercular drug development. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulation approaches were performed on a series of natural and synthetic phenol-based β-CA1 inhibitors. The developed 3D-QSAR model ( r 2  = 0.94, q 2  = 0.86, and pred_r 2  = 0.74) indicated that the steric and electrostatic factors are important parameters to modulate the bioactivity of phenolic compounds. Based on this indication, we designed 72 new phenolic inhibitors, out of which two compounds (D25 and D50) effectively stabilized β-CA1 receptor and, thus, are potential candidates for new generation antitubercular drug discovery program.

COLLABORATIVE RESEARCH AND DEVELOPMENT (CR&D) Delivery Order 0059: Molecular Dynamics Modeling Support

DTIC Science & Technology

2008-03-01

Molecular Dynamics Simulations 5 Theory: Equilibrium Molecular Dynamics Simulations 6 Theory: Non...Equilibrium Molecular Dynamics Simulations 8 Carbon Nanotube Simulations : Approach and results from equilibrium and non-equilibrium molecular dynamics ...touched from the perspective of molecular dynamics simulations . However, ordered systems such as “Carbon Nanotubes” have been investigated in terms

An Integrated In Silico Method to Discover Novel Rock1 Inhibitors: Multi- Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening.

PubMed

Chen, Haining; Li, Sijia; Hu, Yajiao; Chen, Guo; Jiang, Qinglin; Tong, Rongsheng; Zang, Zhihe; Cai, Lulu

2016-01-01

Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is an important regulator of focal adhesion, actomyosin contraction and cell motility. In this manuscript, a combination of the multi-complex-based pharmacophore (MCBP), molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of multipharmacophore- based virtual screening (PBVS) and ensemble docking-based virtual screening (DBVS) methods were used for retrieving novel ROCK1 inhibitors from the natural products database embedded in the ZINC database. Ten hit compounds were selected from the hit compounds, and five compounds were tested experimentally. Thus, these results may provide valuable information for further discovery of more novel ROCK1 inhibitors.

Particle-based simulations of polarity establishment reveal stochastic promotion of Turing pattern formation

PubMed Central

Ramirez, Samuel A.; Elston, Timothy C.

2018-01-01

Polarity establishment, the spontaneous generation of asymmetric molecular distributions, is a crucial component of many cellular functions. Saccharomyces cerevisiae (yeast) undergoes directed growth during budding and mating, and is an ideal model organism for studying polarization. In yeast and many other cell types, the Rho GTPase Cdc42 is the key molecular player in polarity establishment. During yeast polarization, multiple patches of Cdc42 initially form, then resolve into a single front. Because polarization relies on strong positive feedback, it is likely that the amplification of molecular-level fluctuations underlies the generation of multiple nascent patches. In the absence of spatial cues, these fluctuations may be key to driving polarization. Here we used particle-based simulations to investigate the role of stochastic effects in a Turing-type model of yeast polarity establishment. In the model, reactions take place either between two molecules on the membrane, or between a cytosolic and a membrane-bound molecule. Thus, we developed a computational platform that explicitly simulates molecules at and near the cell membrane, and implicitly handles molecules away from the membrane. To evaluate stochastic effects, we compared particle simulations to deterministic reaction-diffusion equation simulations. Defining macroscopic rate constants that are consistent with the microscopic parameters for this system is challenging, because diffusion occurs in two dimensions and particles exchange between the membrane and cytoplasm. We address this problem by empirically estimating macroscopic rate constants from appropriately designed particle-based simulations. Ultimately, we find that stochastic fluctuations speed polarity establishment and permit polarization in parameter regions predicted to be Turing stable. These effects can operate at Cdc42 abundances expected of yeast cells, and promote polarization on timescales consistent with experimental results. To our knowledge, our work represents the first particle-based simulations of a model for yeast polarization that is based on a Turing mechanism. PMID:29529021

UNRES server for physics-based coarse-grained simulations and prediction of protein structure, dynamics and thermodynamics.

PubMed

Czaplewski, Cezary; Karczynska, Agnieszka; Sieradzan, Adam K; Liwo, Adam

2018-04-30

A server implementation of the UNRES package (http://www.unres.pl) for coarse-grained simulations of protein structures with the physics-based UNRES model, coined a name UNRES server, is presented. In contrast to most of the protein coarse-grained models, owing to its physics-based origin, the UNRES force field can be used in simulations, including those aimed at protein-structure prediction, without ancillary information from structural databases; however, the implementation includes the possibility of using restraints. Local energy minimization, canonical molecular dynamics simulations, replica exchange and multiplexed replica exchange molecular dynamics simulations can be run with the current UNRES server; the latter are suitable for protein-structure prediction. The user-supplied input includes protein sequence and, optionally, restraints from secondary-structure prediction or small x-ray scattering data, and simulation type and parameters which are selected or typed in. Oligomeric proteins, as well as those containing D-amino-acid residues and disulfide links can be treated. The output is displayed graphically (minimized structures, trajectories, final models, analysis of trajectory/ensembles); however, all output files can be downloaded by the user. The UNRES server can be freely accessed at http://unres-server.chem.ug.edu.pl.

Melt-growth dynamics in CdTe crystals

DOE PAGES

Zhou, X. W.; Ward, D. K.; Wong, B. M.; ...

2012-06-01

We use a new, quantum-mechanics-based bond-order potential (BOP) to reveal melt growth dynamics and fine scale defect formation mechanisms in CdTe crystals. Previous molecular dynamics simulations of semiconductors have shown qualitatively incorrect behavior due to the lack of an interatomic potential capable of predicting both crystalline growth and property trends of many transitional structures encountered during the melt → crystal transformation. Here, we demonstrate successful molecular dynamics simulations of melt growth in CdTe using a BOP that significantly improves over other potentials on property trends of different phases. Our simulations result in a detailed understanding of defect formation during themore » melt growth process. Equally important, we show that the new BOP enables defect formation mechanisms to be studied at a scale level comparable to empirical molecular dynamics simulation methods with a fidelity level approaching quantum-mechanical methods.« less

Crystal MD: The massively parallel molecular dynamics software for metal with BCC structure

NASA Astrophysics Data System (ADS)

Hu, Changjun; Bai, He; He, Xinfu; Zhang, Boyao; Nie, Ningming; Wang, Xianmeng; Ren, Yingwen

2017-02-01

Material irradiation effect is one of the most important keys to use nuclear power. However, the lack of high-throughput irradiation facility and knowledge of evolution process, lead to little understanding of the addressed issues. With the help of high-performance computing, we could make a further understanding of micro-level-material. In this paper, a new data structure is proposed for the massively parallel simulation of the evolution of metal materials under irradiation environment. Based on the proposed data structure, we developed the new molecular dynamics software named Crystal MD. The simulation with Crystal MD achieved over 90% parallel efficiency in test cases, and it takes more than 25% less memory on multi-core clusters than LAMMPS and IMD, which are two popular molecular dynamics simulation software. Using Crystal MD, a two trillion particles simulation has been performed on Tianhe-2 cluster.

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

Antonelli, Perry Edward

A low-level model-to-model interface is presented that will enable independent models to be linked into an integrated system of models. The interface is based on a standard set of functions that contain appropriate export and import schemas that enable models to be linked with no changes to the models themselves. These ideas are presented in the context of a specific multiscale material problem that couples atomistic-based molecular dynamics calculations to continuum calculations of fluid ow. These simulations will be used to examine the influence of interactions of the fluid with an adjacent solid on the fluid ow. The interface willmore » also be examined by adding it to an already existing modeling code, Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and comparing it with our own molecular dynamics code.« less

Non-Adiabatic Molecular Dynamics Methods for Materials Discovery

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

Furche, Filipp; Parker, Shane M.; Muuronen, Mikko J.

2017-04-04

The flow of radiative energy in light-driven materials such as photosensitizer dyes or photocatalysts is governed by non-adiabatic transitions between electronic states and cannot be described within the Born-Oppenheimer approximation commonly used in electronic structure theory. The non-adiabatic molecular dynamics (NAMD) methods based on Tully surface hopping and time-dependent density functional theory developed in this project have greatly extended the range of molecular materials that can be tackled by NAMD simulations. New algorithms to compute molecular excited state and response properties efficiently were developed. Fundamental limitations of common non-linear response methods were discovered and characterized. Methods for accurate computations ofmore » vibronic spectra of materials such as black absorbers were developed and applied. It was shown that open-shell TDDFT methods capture bond breaking in NAMD simulations, a longstanding challenge for single-reference molecular dynamics simulations. The methods developed in this project were applied to study the photodissociation of acetaldehyde and revealed that non-adiabatic effects are experimentally observable in fragment kinetic energy distributions. Finally, the project enabled the first detailed NAMD simulations of photocatalytic water oxidation by titania nanoclusters, uncovering the mechanism of this fundamentally important reaction for fuel generation and storage.« less

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.

In silico simulations of tunneling barrier measurements for molecular orbital-mediated junctions: A molecular orbital theory approach to scanning tunneling microscopy

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

Terryn, Raymond J.; Sriraman, Krishnan; Olson, Joel A., E-mail: jolson@fit.edu

A new simulator for scanning tunneling microscopy (STM) is presented based on the linear combination of atomic orbitals molecular orbital (LCAO-MO) approximation for the effective tunneling Hamiltonian, which leads to the convolution integral when applied to the tip interaction with the sample. This approach intrinsically includes the structure of the STM tip. Through this mechanical emulation and the tip-inclusive convolution model, dI/dz images for molecular orbitals (which are closely associated with apparent barrier height, ϕ{sub ap}) are reported for the first time. For molecular adsorbates whose experimental topographic images correspond well to isolated-molecule quantum chemistry calculations, the simulator makes accuratemore » predictions, as illustrated by various cases. Distortions in these images due to the tip are shown to be in accord with those observed experimentally and predicted by other ab initio considerations of tip structure. Simulations of the tunneling current dI/dz images are in strong agreement with experiment. The theoretical framework provides a solid foundation which may be applied to LCAO cluster models of adsorbate–substrate systems, and is extendable to emulate several aspects of functional STM operation.« less

Incremental update of electrostatic interactions in adaptively restrained particle simulations.

PubMed

Edorh, Semeho Prince A; Redon, Stéphane

2018-04-06

The computation of long-range potentials is one of the demanding tasks in Molecular Dynamics. During the last decades, an inventive panoply of methods was developed to reduce the CPU time of this task. In this work, we propose a fast method dedicated to the computation of the electrostatic potential in adaptively restrained systems. We exploit the fact that, in such systems, only some particles are allowed to move at each timestep. We developed an incremental algorithm derived from a multigrid-based alternative to traditional Fourier-based methods. Our algorithm was implemented inside LAMMPS, a popular molecular dynamics simulation package. We evaluated the method on different systems. We showed that the new algorithm's computational complexity scales with the number of active particles in the simulated system, and is able to outperform the well-established Particle Particle Particle Mesh (P3M) for adaptively restrained simulations. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

A multiscale computational approach to dissect early events in the Erb family receptor mediated activation, differential signaling, and relevance to oncogenic transformations.

PubMed

Liu, Yingting; Purvis, Jeremy; Shih, Andrew; Weinstein, Joshua; Agrawal, Neeraj; Radhakrishnan, Ravi

2007-06-01

We describe a hierarchical multiscale computational approach based on molecular dynamics simulations, free energy-based molecular docking simulations, deterministic network-based kinetic modeling, and hybrid discrete/continuum stochastic dynamics protocols to study the dimer-mediated receptor activation characteristics of the Erb family receptors, specifically the epidermal growth factor receptor (EGFR). Through these modeling approaches, we are able to extend the prior modeling of EGF-mediated signal transduction by considering specific EGFR tyrosine kinase (EGFRTK) docking interactions mediated by differential binding and phosphorylation of different C-terminal peptide tyrosines on the RTK tail. By modeling signal flows through branching pathways of the EGFRTK resolved on a molecular basis, we are able to transcribe the effects of molecular alterations in the receptor (e.g., mutant forms of the receptor) to differing kinetic behavior and downstream signaling response. Our molecular dynamics simulations show that the drug sensitizing mutation (L834R) of EGFR stabilizes the active conformation to make the system constitutively active. Docking simulations show preferential characteristics (for wildtype vs. mutant receptors) in inhibitor binding as well as preferential enhancement of phosphorylation of particular substrate tyrosines over others. We find that in comparison to the wildtype system, the L834R mutant RTK preferentially binds the inhibitor erlotinib, as well as preferentially phosphorylates the substrate tyrosine Y1068 but not Y1173. We predict that these molecular level changes result in preferential activation of the Akt signaling pathway in comparison to the Erk signaling pathway for cells with normal EGFR expression. For cells with EGFR over expression, the mutant over activates both Erk and Akt pathways, in comparison to wildtype. These results are consistent with qualitative experimental measurements reported in the literature. We discuss these consequences in light of how the network topology and signaling characteristics of altered (mutant) cell lines are shaped differently in relationship to native cell lines.

Investigations of FAK inhibitors: a combination of 3D-QSAR, docking, and molecular dynamics simulations studies.

PubMed

Cheng, Peng; Li, Jiaojiao; Wang, Juan; Zhang, Xiaoyun; Zhai, Honglin

2018-05-01

Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates integrin and growth factor signaling pathways, which is a promising therapeutic target because of involving in cancer cell migration, proliferation, and survival. To investigate the mechanism between FAK and triazinic inhibitors and design high activity inhibitors, a molecular modeling integrated with 3D-QSAR, molecular docking, molecular dynamics simulations, and binding free energy calculations was performed. The optimum CoMFA and CoMSIA models showed good reliability and satisfactory predictability (with Q 2  = 0.663, R 2  = 0.987, [Formula: see text] = 0.921 and Q 2  = 0.670, R 2  = 0.981, [Formula: see text] = 0.953). Its contour maps could provide structural features to improve inhibitory activity. Furthermore, a good consistency between contour maps, docking, and molecular dynamics simulations strongly demonstrates that the molecular modeling is reliable. Based on it, we designed several new compounds and their inhibitory activities were validated by the molecular models. We expect our studies could bring new ideas to promote the development of novel inhibitors with higher inhibitory activity for FAK.

GENESIS: a hybrid-parallel and multi-scale molecular dynamics simulator with enhanced sampling algorithms for biomolecular and cellular simulations.

PubMed

Jung, Jaewoon; Mori, Takaharu; Kobayashi, Chigusa; Matsunaga, Yasuhiro; Yoda, Takao; Feig, Michael; Sugita, Yuji

2015-07-01

GENESIS (Generalized-Ensemble Simulation System) is a new software package for molecular dynamics (MD) simulations of macromolecules. It has two MD simulators, called ATDYN and SPDYN. ATDYN is parallelized based on an atomic decomposition algorithm for the simulations of all-atom force-field models as well as coarse-grained Go-like models. SPDYN is highly parallelized based on a domain decomposition scheme, allowing large-scale MD simulations on supercomputers. Hybrid schemes combining OpenMP and MPI are used in both simulators to target modern multicore computer architectures. Key advantages of GENESIS are (1) the highly parallel performance of SPDYN for very large biological systems consisting of more than one million atoms and (2) the availability of various REMD algorithms (T-REMD, REUS, multi-dimensional REMD for both all-atom and Go-like models under the NVT, NPT, NPAT, and NPγT ensembles). The former is achieved by a combination of the midpoint cell method and the efficient three-dimensional Fast Fourier Transform algorithm, where the domain decomposition space is shared in real-space and reciprocal-space calculations. Other features in SPDYN, such as avoiding concurrent memory access, reducing communication times, and usage of parallel input/output files, also contribute to the performance. We show the REMD simulation results of a mixed (POPC/DMPC) lipid bilayer as a real application using GENESIS. GENESIS is released as free software under the GPLv2 licence and can be easily modified for the development of new algorithms and molecular models. WIREs Comput Mol Sci 2015, 5:310-323. doi: 10.1002/wcms.1220.

Studies on thermal decomposition behaviors of polypropylene using molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Huang, Jinbao; He, Chao; Tong, Hong; Pan, Guiying

2017-11-01

Polypropylene (PP) is one of the main components of waste plastics. In order to understand the mechanism of PP thermal decomposition, the pyrolysis behaviour of PP has been simulated from 300 to 1000 K in periodic boundary conditions by molecular dynamic method, based on AMBER force field. The simulation results show that the pyrolysis process of PP can mostly be divided into three stages: low temperature pyrolysis stage, intermediate temperature stage and high temperature pyrolysis stage. PP pyrolysis is typical of random main-chain scission, and the possible formation mechanism of major pyrolysis products was analyzed.

A new battery-charging method suggested by molecular dynamics simulations.

PubMed

Abou Hamad, Ibrahim; Novotny, M A; Wipf, D O; Rikvold, P A

2010-03-20

Based on large-scale molecular dynamics simulations, we propose a new charging method that should be capable of charging a lithium-ion battery in a fraction of the time needed when using traditional methods. This charging method uses an additional applied oscillatory electric field. Our simulation results show that this charging method offers a great reduction in the average intercalation time for Li(+) ions, which dominates the charging time. The oscillating field not only increases the diffusion rate of Li(+) ions in the electrolyte but, more importantly, also enhances intercalation by lowering the corresponding overall energy barrier.

Study on the stability of the DNA hairpin d(ATCCAT-GTTA-TAGGAT) employing molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Wu, Sangwook

2015-03-01

DNA hairpin plays a critical role in the regulation of gene expression and DNA recombination. We studied the conformation of the DNA hairpin, d(ATCCAT-GTTA-TAGGAT) (PDB id:1AC7), employing molecular dynamics (MD) simulation. Despite the non-canonical Watson-Crick base pair (G:A) in the tetraloop (GTTA), MD simulation reveals that the conformation of the DNA hairpin is remarkably stable. In this study, we discuss about the physical/chemical origin of the stability of the DNA hairpin. Department of Biomedical Engineering, Korea University, Seoul 136-703, Korea.

Efficient molecular dynamics simulations with many-body potentials on graphics processing units

NASA Astrophysics Data System (ADS)

Fan, Zheyong; Chen, Wei; Vierimaa, Ville; Harju, Ari

2017-09-01

Graphics processing units have been extensively used to accelerate classical molecular dynamics simulations. However, there is much less progress on the acceleration of force evaluations for many-body potentials compared to pairwise ones. In the conventional force evaluation algorithm for many-body potentials, the force, virial stress, and heat current for a given atom are accumulated within different loops, which could result in write conflict between different threads in a CUDA kernel. In this work, we provide a new force evaluation algorithm, which is based on an explicit pairwise force expression for many-body potentials derived recently (Fan et al., 2015). In our algorithm, the force, virial stress, and heat current for a given atom can be accumulated within a single thread and is free of write conflicts. We discuss the formulations and algorithms and evaluate their performance. A new open-source code, GPUMD, is developed based on the proposed formulations. For the Tersoff many-body potential, the double precision performance of GPUMD using a Tesla K40 card is equivalent to that of the LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator) molecular dynamics code running with about 100 CPU cores (Intel Xeon CPU X5670 @ 2.93 GHz).

Modeling of crack growth under mixed-mode loading by a molecular dynamics method and a linear fracture mechanics approach

NASA Astrophysics Data System (ADS)

Stepanova, L. V.

2017-12-01

Atomistic simulations of the central crack growth process in an infinite plane medium under mixed-mode loading using Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS), a classical molecular dynamics code, are performed. The inter-atomic potential used in this investigation is the Embedded Atom Method (EAM) potential. Plane specimens with an initial central crack are subjected to mixed-mode loadings. The simulation cell contains 400,000 atoms. The crack propagation direction angles under different values of the mixity parameter in a wide range of values from pure tensile loading to pure shear loading in a wide range of temperatures (from 0.1 K to 800 K) are obtained and analyzed. It is shown that the crack propagation direction angles obtained by molecular dynamics coincide with the crack propagation direction angles given by the multi-parameter fracture criteria based on the strain energy density and the multi-parameter description of the crack-tip fields. The multi-parameter fracture criteria are based on the multi-parameter stress field description taking into account the higher order terms of the Williams series expansion of the crack tip fields.

Thermophysical properties of energetic ionic liquids/nitric acid mixtures: Insights from molecular dynamics simulationsa)

NASA Astrophysics Data System (ADS)

Hooper, Justin B.; Smith, Grant D.; Bedrov, Dmitry

2013-09-01

Molecular dynamics (MD) simulations of mixtures of the room temperature ionic liquids (ILs) 1-butyl-4-methyl imidazolium [BMIM]/dicyanoamide [DCA] and [BMIM][NO3-] with HNO3 have been performed utilizing the polarizable, quantum chemistry based APPLE&P® potential. Experimentally it has been observed that [BMIM][DCA] exhibits hypergolic behavior when mixed with HNO3 while [BMIM][NO3-] does not. The structural, thermodynamic, and transport properties of the IL/HNO3 mixtures have been determined from equilibrium MD simulations over the entire composition range (pure IL to pure HNO3) based on bulk simulations. Additional (non-equilibrium) simulations of the composition profile for IL/HNO3 interfaces as a function of time have been utilized to estimate the composition dependent mutual diffusion coefficients for the mixtures. The latter have been employed in continuum-level simulations in order to examine the nature (composition and width) of the IL/HNO3 interfaces on the millisecond time scale.

Co-pyrolysis mechanism of seaweed polysaccharides and cellulose based on macroscopic experiments and molecular simulations.

PubMed

Wang, Shuang; Xia, Zhen; Hu, Yamin; He, Zhixia; Uzoejinwa, Benjamin Bernard; Wang, Qian; Cao, Bin; Xu, Shanna

2017-03-01

Co-pyrolysis conversion of seaweed (Enteromorpha clathrat and Sargassum fusiforme) polysaccharides and cellulose has been investigated. From the Py-GC/MS results, Enteromorpha clathrata (EN) polysaccharides pyrolysis mainly forms furans; while the products of Sargassum fusiforme (SA) polysaccharides pyrolysis are mainly acid esters. The formation mechanisms of H 2 O, CO 2 , and SO 2 during the pyrolysis of seaweed polysaccharides were analyzed using the thermogravimetric-mass spectrometry. Meanwhile the pyrolysis of seaweed polysaccharide based on the Amber and the ReaxFF force fields, has also been proposed and simulated respectively. The simulation results coincided with the experimental results. During the fast pyrolysis, strong synergistic effects among cellulose and seaweed polysaccharide molecules have been simulated. By comparing the experimental and simulation value, it has been found that co-pyrolysis could increase the number of molecular fragments, increase the pyrolysis conversion rate, and increase gas production rate at the middle temperature range. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Hugoniot adiabat of crystalline copper based on molecular dynamics simulation and semiempirical equation of state

NASA Astrophysics Data System (ADS)

Gubin, S. A.; Maklashova, I. V.; Mel'nikov, I. N.

2018-01-01

The molecular dynamics (MD) method was used for prediction of properties of copper under shock-wave compression and clarification of the melting region of crystal copper. The embedded atom potential was used for the interatomic interaction. Parameters of Hugonoit adiabats of solid and liquid phases of copper calculated by the semiempirical Grüneisen equation of state are consistent with the results of MD simulations and experimental data. MD simulation allows to visualize the structure of cooper on the atomistic level. The analysis of the radial distribution function and the standard deviation by MD modeling allows to predict the melting area behind the shock wave front. These MD simulation data are required to verify the wide-range equation of state of metals. The melting parameters of copper based on MD simulations and semiempirical equations of state are consistent with experimental and theoretical data, including the region of the melting point of copper.

Dispersing Zwitterions into Comb Polymers for Nonviral Transfection: Experiments and Molecular Simulation.

PubMed

Ghobadi, Ahmadreza F; Letteri, Rachel; Parelkar, Sangram S; Zhao, Yue; Chan-Seng, Delphine; Emrick, Todd; Jayaraman, Arthi

2016-02-08

Polymer-based gene delivery vehicles benefit from the presence of hydrophilic groups that mitigate the inherent toxicity of polycations and that provide tunable polymer-DNA binding strength and stable complexes (polyplexes). However, hydrophilic groups screen charge, and as such can reduce cell uptake and transfection efficiency. We report the effect of embedding zwitterionic sulfobetaine (SB) groups in cationic comb polymers, using a combination of experiments and molecular simulations. Ring-opening metathesis polymerization (ROMP) produced comb polymers with tetralysine (K4) and SB pendent groups. Dynamic light scattering, zeta potential measurements, and fluorescence-based experiments, together with coarse-grained molecular dynamics simulations, described the effect of SB groups on the size, shape, surface charge, composition, and DNA binding strength of polyplexes formed using these comb polymers. Experiments and simulations showed that increasing SB composition in the comb polymers decreased polymer-DNA binding strength, while simulations indicated that the SB groups distributed throughout the polyplex. This allows polyplexes to maintain a positive surface charge and provide high levels of gene expression in live cells. Notably, comb polymers with nearly 50 mol % SB form polyplexes that exhibit positive surface charge similarly as polyplexes formed from purely cationic comb polymers, indicating the ability to introduce an appreciable amount of SB functionality without screening surface charge. This integrated simulation-experimental study demonstrates the effectiveness of incorporating zwitterions in polyplexes, while guiding the design of new and effective gene delivery vectors.

Predictive Finite Rate Model for Oxygen-Carbon Interactions at High Temperature

NASA Astrophysics Data System (ADS)

Poovathingal, Savio

An oxidation model for carbon surfaces is developed to predict ablation rates for carbon heat shields used in hypersonic vehicles. Unlike existing empirical models, the approach used here was to probe gas-surface interactions individually and then based on an understanding of the relevant fundamental processes, build a predictive model that would be accurate over a wide range of pressures and temperatures, and even microstructures. Initially, molecular dynamics was used to understand the oxidation processes on the surface. The molecular dynamics simulations were compared to molecular beam experiments and good qualitative agreement was observed. The simulations reproduced cylindrical pitting observed in the experiments where oxidation was rapid and primarily occurred around a defect. However, the studies were limited to small systems at low temperatures and could simulate time scales only of the order of nanoseconds. Molecular beam experiments at high surface temperature indicated that a majority of surface reaction products were produced through thermal mechanisms. Since the reactions were thermal, they occurred over long time scales which were computationally prohibitive for molecular dynamics to simulate. The experiments provided detailed dynamical data on the scattering of O, O2, CO, and CO2 and it was found that the data from molecular beam experiments could be used directly to build a model. The data was initially used to deduce surface reaction probabilities at 800 K. The reaction probabilities were then incorporated into the direct simulation Monte Carlo (DSMC) method. Simulations were performed where the microstructure was resolved and dissociated oxygen convected and diffused towards it. For a gas-surface temperature of 800 K, it was found that despite CO being the dominant surface reaction product, a gas-phase reaction forms significant CO2 within the microstructure region. It was also found that surface area did not play any role in concentration of reaction products because the reaction probabilities were in the diffusion dominant regime. The molecular beam data at different surface temperatures was then used to build a finite rate model. Each reaction mechanism and all rate parameters of the new model were determined individually based on the molecular beam data. Despite the experiments being performed at near vacuum conditions, the finite rate model developed using the data could be used at pressures and temperatures relevant to hypersonic conditions. The new model was implemented in a computational fluid dynamics (CFD) solver and flow over a hypersonic vehicle was simulated. The new model predicted similar overall mass loss rates compared to existing models, however, the individual species production rates were completely different. The most notable difference was that the new model (based on molecular beam data) predicts CO as the oxidation reaction product with virtually no CO2 production, whereas existing models predict the exact opposite trend. CO being the dominant oxidation product is consistent with recent high enthalpy wind tunnel experiments. The discovery that measurements taken in molecular beam facilities are able to determine individual reaction mechanisms, including dependence on surface coverage, opens up an entirely new way of constructing ablation models.

A hybrid algorithm for parallel molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Mangiardi, Chris M.; Meyer, R.

2017-10-01

This article describes algorithms for the hybrid parallelization and SIMD vectorization of molecular dynamics simulations with short-range forces. The parallelization method combines domain decomposition with a thread-based parallelization approach. The goal of the work is to enable efficient simulations of very large (tens of millions of atoms) and inhomogeneous systems on many-core processors with hundreds or thousands of cores and SIMD units with large vector sizes. In order to test the efficiency of the method, simulations of a variety of configurations with up to 74 million atoms have been performed. Results are shown that were obtained on multi-core systems with Sandy Bridge and Haswell processors as well as systems with Xeon Phi many-core processors.

POLYANA-A tool for the calculation of molecular radial distribution functions based on Molecular Dynamics trajectories

NASA Astrophysics Data System (ADS)

Dimitroulis, Christos; Raptis, Theophanes; Raptis, Vasilios

2015-12-01

We present an application for the calculation of radial distribution functions for molecular centres of mass, based on trajectories generated by molecular simulation methods (Molecular Dynamics, Monte Carlo). When designing this application, the emphasis was placed on ease of use as well as ease of further development. In its current version, the program can read trajectories generated by the well-known DL_POLY package, but it can be easily extended to handle other formats. It is also very easy to 'hack' the program so it can compute intermolecular radial distribution functions for groups of interaction sites rather than whole molecules.

Assessing the accuracy of improved force-matched water models derived from Ab initio molecular dynamics simulations.

PubMed

Köster, Andreas; Spura, Thomas; Rutkai, Gábor; Kessler, Jan; Wiebeler, Hendrik; Vrabec, Jadran; Kühne, Thomas D

2016-07-15

The accuracy of water models derived from ab initio molecular dynamics simulations by means on an improved force-matching scheme is assessed for various thermodynamic, transport, and structural properties. It is found that although the resulting force-matched water models are typically less accurate than fully empirical force fields in predicting thermodynamic properties, they are nevertheless much more accurate than generally appreciated in reproducing the structure of liquid water and in fact superseding most of the commonly used empirical water models. This development demonstrates the feasibility to routinely parametrize computationally efficient yet predictive potential energy functions based on accurate ab initio molecular dynamics simulations for a large variety of different systems. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Moving Contact Lines: Linking Molecular Dynamics and Continuum-Scale Modeling.

PubMed

Smith, Edward R; Theodorakis, Panagiotis E; Craster, Richard V; Matar, Omar K

2018-05-17

Despite decades of research, the modeling of moving contact lines has remained a formidable challenge in fluid dynamics whose resolution will impact numerous industrial, biological, and daily life applications. On the one hand, molecular dynamics (MD) simulation has the ability to provide unique insight into the microscopic details that determine the dynamic behavior of the contact line, which is not possible with either continuum-scale simulations or experiments. On the other hand, continuum-based models provide a link to the macroscopic description of the system. In this Feature Article, we explore the complex range of physical factors, including the presence of surfactants, which governs the contact line motion through MD simulations. We also discuss links between continuum- and molecular-scale modeling and highlight the opportunities for future developments in this area.

Combined 3D-QSAR, molecular docking, molecular dynamics simulation, and binding free energy calculation studies on the 5-hydroxy-2H-pyridazin-3-one derivatives as HCV NS5B polymerase inhibitors.

PubMed

Yu, Haijing; Fang, Yu; Lu, Xia; Liu, Yongjuan; Zhang, Huabei

2014-01-01

The NS5B RNA-dependent RNA polymerase (RdRP) is a promising therapeutic target for developing novel anti-hepatitis C virus (HCV) drugs. In this work, a combined molecular modeling study was performed on a series of 193 5-hydroxy-2H-pyridazin-3-one derivatives as inhibitors of HCV NS5B Polymerase. The best 3D-QSAR models, including CoMFA and CoMSIA, are based on receptor (or docking). Furthermore, a 40-ns molecular dynamics (MD) simulation and binding free energy calculations using docked structures of NS5B with ten compounds, which have diverse structures and pIC50 values, were employed to determine the detailed binding process and to compare the binding modes of the inhibitors with different activities. On one side, the stability and rationality of molecular docking and 3D-QSAR results were validated by MD simulation. The binding free energies calculated by the MM-PBSA method gave a good correlation with the experimental biological activity. On the other side, by analyzing some differences between the molecular docking and the MD simulation results, we can find that the MD simulation could also remedy the defects of molecular docking. The analyses of the combined molecular modeling results have identified that Tyr448, Ser556, and Asp318 are the key amino acid residues in the NS5B binding pocket. The results from this study can provide some insights into the development of novel potent NS5B inhibitors. © 2013 John Wiley & Sons A/S.

Morphological diagnostics of star formation in molecular clouds

NASA Astrophysics Data System (ADS)

Beaumont, Christopher Norris

Molecular clouds are the birth sites of all star formation in the present-day universe. They represent the initial conditions of star formation, and are the primary medium by which stars transfer energy and momentum back to parsec scales. Yet, the physical evolution of molecular clouds remains poorly understood. This is not due to a lack of observational data, nor is it due to an inability to simulate the conditions inside molecular clouds. Instead, the physics and structure of the interstellar medium are sufficiently complex that interpreting molecular cloud data is very difficult. This dissertation mitigates this problem, by developing more sophisticated ways to interpret morphological information in molecular cloud observations and simulations. In particular, I have focused on leveraging machine learning techniques to identify physically meaningful substructures in the interstellar medium, as well as techniques to inter-compare molecular cloud simulations to observations. These contributions make it easier to understand the interplay between molecular clouds and star formation. Specific contributions include: new insight about the sheet-like geometry of molecular clouds based on observations of stellar bubbles; a new algorithm to disambiguate overlapping yet morphologically distinct cloud structures; a new perspective on the relationship between molecular cloud column density distributions and the sizes of cloud substructures; a quantitative analysis of how projection effects affect measurements of cloud properties; and an automatically generated, statistically-calibrated catalog of bubbles identified from their infrared morphologies.

Temperature specification in atomistic molecular dynamics and its impact on simulation efficacy

NASA Astrophysics Data System (ADS)

Ocaya, R. O.; Terblans, J. J.

2017-10-01

Temperature is a vital thermodynamical function for physical systems. Knowledge of system temperature permits assessment of system ergodicity, entropy, system state and stability. Rapid theoretical and computational developments in the fields of condensed matter physics, chemistry, material science, molecular biology, nanotechnology and others necessitate clarity in the temperature specification. Temperature-based materials simulations, both standalone and distributed computing, are projected to grow in prominence over diverse research fields. In this article we discuss the apparent variability of temperature modeling formalisms used currently in atomistic molecular dynamics simulations, with respect to system energetics,dynamics and structural evolution. Commercial simulation programs, which by nature are heuristic, do not openly discuss this fundamental question. We address temperature specification in the context of atomistic molecular dynamics. We define a thermostat at 400K relative to a heat bath at 300K firstly using a modified ab-initio Newtonian method, and secondly using a Monte-Carlo method. The thermostatic vacancy formation and cohesion energies, equilibrium lattice constant for FCC copper is then calculated. Finally we compare and contrast the results.

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

Engineering molecular machines

NASA Astrophysics Data System (ADS)

Erman, Burak

2016-04-01

Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

Gromita: a fully integrated graphical user interface to gromacs 4.

PubMed

Sellis, Diamantis; Vlachakis, Dimitrios; Vlassi, Metaxia

2009-09-07

Gromita is a fully integrated and efficient graphical user interface (GUI) to the recently updated molecular dynamics suite Gromacs, version 4. Gromita is a cross-platform, perl/tcl-tk based, interactive front end designed to break the command line barrier and introduce a new user-friendly environment to run molecular dynamics simulations through Gromacs. Our GUI features a novel workflow interface that guides the user through each logical step of the molecular dynamics setup process, making it accessible to both advanced and novice users. This tool provides a seamless interface to the Gromacs package, while providing enhanced functionality by speeding up and simplifying the task of setting up molecular dynamics simulations of biological systems. Gromita can be freely downloaded from http://bio.demokritos.gr/gromita/.

Internal Coordinate Molecular Dynamics: A Foundation for Multiscale Dynamics

PubMed Central

2015-01-01

Internal coordinates such as bond lengths, bond angles, and torsion angles (BAT) are natural coordinates for describing a bonded molecular system. However, the molecular dynamics (MD) simulation methods that are widely used for proteins, DNA, and polymers are based on Cartesian coordinates owing to the mathematical simplicity of the equations of motion. However, constraints are often needed with Cartesian MD simulations to enhance the conformational sampling. This makes the equations of motion in the Cartesian coordinates differential-algebraic, which adversely impacts the complexity and the robustness of the simulations. On the other hand, constraints can be easily placed in BAT coordinates by removing the degrees of freedom that need to be constrained. Thus, the internal coordinate MD (ICMD) offers an attractive alternative to Cartesian coordinate MD for developing multiscale MD method. The torsional MD method is a special adaptation of the ICMD method, where all the bond lengths and bond angles are kept rigid. The advantages of ICMD simulation methods are the longer time step size afforded by freezing high frequency degrees of freedom and performing a conformational search in the more important low frequency torsional degrees of freedom. However, the advancements in the ICMD simulations have been slow and stifled by long-standing mathematical bottlenecks. In this review, we summarize the recent mathematical advancements we have made based on spatial operator algebra, in developing a robust long time scale ICMD simulation toolkit useful for various applications. We also present the applications of ICMD simulations to study conformational changes in proteins and protein structure refinement. We review the advantages of the ICMD simulations over the Cartesian simulations when used with enhanced sampling methods and project the future use of ICMD simulations in protein dynamics. PMID:25517406

Facilitating Students' Interaction with Real Gas Properties Using a Discovery-Based Approach and Molecular Dynamics Simulations

ERIC Educational Resources Information Center

Sweet, Chelsea; Akinfenwa, Oyewumi; Foley, Jonathan J., IV

2018-01-01

We present an interactive discovery-based approach to studying the properties of real gases using simple, yet realistic, molecular dynamics software. Use of this approach opens up a variety of opportunities for students to interact with the behaviors and underlying theories of real gases. Students can visualize gas behavior under a variety of…

Linear Response Path Following: A Molecular Dynamics Method To Simulate Global Conformational Changes of Protein upon Ligand Binding.

PubMed

Tamura, Koichi; Hayashi, Shigehiko

2015-07-14

Molecular functions of proteins are often fulfilled by global conformational changes that couple with local events such as the binding of ligand molecules. High molecular complexity of proteins has, however, been an obstacle to obtain an atomistic view of the global conformational transitions, imposing a limitation on the mechanistic understanding of the functional processes. In this study, we developed a new method of molecular dynamics (MD) simulation called the linear response path following (LRPF) to simulate a protein's global conformational changes upon ligand binding. The method introduces a biasing force based on a linear response theory, which determines a local reaction coordinate in the configuration space that represents linear coupling between local events of ligand binding and global conformational changes and thus provides one with fully atomistic models undergoing large conformational changes without knowledge of a target structure. The overall transition process involving nonlinear conformational changes is simulated through iterative cycles consisting of a biased MD simulation with an updated linear response force and a following unbiased MD simulation for relaxation. We applied the method to the simulation of global conformational changes of the yeast calmodulin N-terminal domain and successfully searched out the end conformation. The atomistically detailed trajectories revealed a sequence of molecular events that properly lead to the global conformational changes and identified key steps of local-global coupling that induce the conformational transitions. The LRPF method provides one with a powerful means to model conformational changes of proteins such as motors and transporters where local-global coupling plays a pivotal role in their functional processes.

An Insilico Design of Nanoclay Based Nanocomposites and Scaffolds in Bone Tissue Engineering

NASA Astrophysics Data System (ADS)

Sharma, Anurag

A multiscale in silico approach to design polymer nanocomposites and scaffolds for bone tissue engineering applications is described in this study. This study focuses on the role of biomaterials design and selection, structural integrity and mechanical properties evolution during degradation and tissue regeneration in the successful design of polymer nanocomposite scaffolds. Polymer nanocomposite scaffolds are synthesized using aminoacid modified montmorillonite nanoclay with biomineralized hydroxyapatite and polycaprolactone (PCL/in situ HAPclay). Representative molecular models of polymer nanocomposite system are systematically developed using molecular dynamics (MD) technique and successfully validated using material characterization techniques. The constant force steered molecular dynamics (fSMD) simulation results indicate a two-phase nanomechanical behavior of the polymer nanocomposite. The MD and fSMD simulations results provide quantitative contributions of molecular interactions between different constituents of representative models and their effect on nanomechanical responses of nanoclay based polymer nanocomposite system. A finite element (FE) model of PCL/in situ HAPclay scaffold is built using micro-computed tomography images and bridging the nanomechanical properties obtained from fSMD simulations into the FE model. A new reduction factor, K is introduced into modeling results to consider the effect of wall porosity of the polymer scaffold. The effect of accelerated degradation under alkaline conditions and human osteoblast cells culture on the evolution of mechanical properties of scaffolds are studied and the damage mechanics based analytical models are developed. Finally, the novel multiscale models are developed that incorporate the complex molecular and microstructural properties, mechanical properties at nanoscale and structural levels and mechanical properties evolution during degradation and tissue formation in the polymer nanocomposite scaffold. Overall, this study provides a leap into methodologies for in silico design of biomaterials for bone tissue engineering applications. Furthermore, as a part of this work, a molecular dynamics study of rice DNA in the presence of single walled carbon nanotube is carried out to understand the role played by molecular interactions in the conformation changes of rice DNA. The simulations results showed wrapping of DNA onto SWCNT, breaking and forming of hydrogen bonds due to unzipping of Watson-Crick (WC) nucleobase pairs and forming of new non-WC nucleobase pairs in DNA.

Nanoscale inhomogeneity and photoacid generation dynamics in extreme ultraviolet resist materials

NASA Astrophysics Data System (ADS)

Wu, Ping-Jui; Wang, Yu-Fu; Chen, Wei-Chi; Wang, Chien-Wei; Cheng, Joy; Chang, Vencent; Chang, Ching-Yu; Lin, John; Cheng, Yuan-Chung

2018-03-01

The development of extreme ultraviolet (EUV) lithography towards the 22 nm node and beyond depends critically on the availability of resist materials that meet stringent control requirements in resolution, line edge roughness, and sensitivity. However, the molecular mechanisms that govern the structure-function relationships in current EUV resist systems are not well understood. In particular, the nanoscale structures of the polymer base and the distributions of photoacid generators (PAGs) should play a critical roles in the performance of a resist system, yet currently available models for photochemical reactions in EUV resist systems are exclusively based on homogeneous bulk models that ignore molecular-level details of solid resist films. In this work, we investigate how microscopic molecular organizations in EUV resist affect photoacid generations in a bottom-up approach that describes structure-dependent electron-transfer dynamics in a solid film model. To this end, molecular dynamics simulations and stimulated annealing are used to obtain structures of a large simulation box containing poly(4-hydroxystyrene) (PHS) base polymers and triphenylsulfonium based PAGs. Our calculations reveal that ion-pair interactions govern the microscopic distributions of the polymer base and PAG molecules, resulting in a highly inhomogeneous system with nonuniform nanoscale chemical domains. Furthermore, the theoretical structures were used in combination of quantum chemical calculations and the Marcus theory to evaluate electron transfer rates between molecular sites, and then kinetic Monte Carlo simulations were carried out to model electron transfer dynamics with molecular structure details taken into consideration. As a result, the portion of thermalized electrons that are absorbed by the PAGs and the nanoscale spatial distribution of generated acids can be estimated. Our data reveal that the nanoscale inhomogeneous distributions of base polymers and PAGs strongly affect the electron transfer and the performance of the resist system. The implications to the performances of EUV resists and key engineering requirements for improved resist systems will also be discussed in this work. Our results shed light on the fundamental structure dependence of photoacid generation and the control of the nanoscale structures as well as base polymer-PAG interactions in EVU resist systems, and we expect these knowledge will be useful for the future development of improved EUV resist systems.

Molecular simulation of water removal from simple gases with zeolite NaA.

PubMed

Csányi, Eva; Ható, Zoltán; Kristóf, Tamás

2012-06-01

Water vapor removal from some simple gases using zeolite NaA was studied by molecular simulation. The equilibrium adsorption properties of H(2)O, CO, H(2), CH(4) and their mixtures in dehydrated zeolite NaA were computed by grand canonical Monte Carlo simulations. The simulations employed Lennard-Jones + Coulomb type effective pair potential models, which are suitable for the reproduction of thermodynamic properties of pure substances. Based on the comparison of the simulation results with experimental data for single-component adsorption at different temperatures and pressures, a modified interaction potential model for the zeolite is proposed. In the adsorption simulations with mixtures presented here, zeolite exhibits extremely high selectivity of water to the investigated weakly polar/non-polar gases demonstrating the excellent dehydration ability of zeolite NaA in engineering applications.

CL-20/DNB co-crystal based PBX with PEG: molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Zhang, Jiang; Gao, Pei; Xiao, Ji Jun; Zhao, Feng; Xiao, He Ming

2016-12-01

Molecular dynamics simulation was carried out for CL-20/DNB co-crystal based PBX (polymer-bonded explosive) blended with polymer PEG (polyethylene glycol). In this paper, the miscibility of the PBX models is investigated through the calculated binding energy. Pair correlation function (PCF) analysis is applied to study the interaction of the interface structures in the PBX models. The mechanical properties of PBXs are also discussed to understand the change of the mechanical properties after adding the polymer. Moreover, the calculated diffusion coefficients of the interfacial explosive molecules are used to discuss the dispersal ability of CL-20 and DNB molecules in the interface layer.

Stability of vacancy-type defect clusters in Ni based on first-principles and molecular dynamics simulations

DOE PAGES

Zhao, Shijun; Zhang, Yanwen; Weber, William J.

2017-10-17

Using first-principles calculations based on density-functional theory, the energetics of different vacancy-type defects, including voids, stacking fault tetrahedra (SFT) and vacancy loops, in Ni are investigated. It is found that voids are more stable than SFT at 0 K, which is also the case after taking into account the volumetric strains. By carrying out ab initio molecular dynamics simulations at temperatures up to 1000 K, direct transformations from vacancy loops and voids into SFT are observed. Our results suggest the importance of temperature effects in determining thermodynamic stability of vacancy clusters in face-centered cubic metals.

Atomistic simulation of graphene-based polymer nanocomposites

NASA Astrophysics Data System (ADS)

Rissanou, Anastassia N.; Bačová, Petra; Harmandaris, Vagelis

2016-05-01

Polymer/graphene nanostructured systems are hybrid materials which have attracted great attention the last years both for scientific and technological reasons. In the present work atomistic Molecular Dynamics simulations are performed for the study of graphene-based polymer nanocomposites composed of pristine, hydrogenated and carboxylated graphene sheets dispersed in polar (PEO) and nonpolar (PE) short polymer matrices (i.e., matrices containing chains of low molecular weight). Our focus is twofold; the one is the study of the structural and dynamical properties of short polymer chains and the way that they are affected by functionalized graphene sheets while the other is the effect of the polymer matrices on the behavior of graphene sheets.

Hydrogen-vacancy-dislocation interactions in α-Fe

NASA Astrophysics Data System (ADS)

Tehranchi, A.; Zhang, X.; Lu, G.; Curtin, W. A.

2017-02-01

Atomistic simulations of the interactions between dislocations, hydrogen atoms, and vacancies are studied to assess the viability of a recently proposed mechanism for the formation of nanoscale voids in Fe-based steels in the presence of hydrogen. Quantum-mechanics/molecular-mechanics method calculations confirm molecular statics simulations based on embedded atom method (EAM) potential showing that individual vacancies on the compressive side of an edge dislocation can be transported with the dislocation as it glides. Molecular dynamics simulations based on EAM potential then show, however, that vacancy clusters in the glide plane of an approaching dislocation are annihilated or reduced in size by the creation of a double-jog/climb process that is driven by the huge reduction in energy accompanying vacancy annihilation. The effectiveness of annihilation/reduction processes is not reduced by the presence of hydrogen in the vacancy clusters because typical V-H cluster binding energies are much lower than the vacancy formation energy, except at very high hydrogen content in the cluster. Analysis of a range of configurations indicates that hydrogen plays no special role in stabilizing nanovoids against jog formation processes that shrink voids. Experimental observations of nanovoids on the fracture surfaces of steels must be due to as-yet undetermined processes.

Phenomenological and molecular-level Petri net modeling and simulation of long-term potentiation.

PubMed

Hardy, S; Robillard, P N

2005-10-01

Petri net-based modeling methods have been used in many research projects to represent biological systems. Among these, the hybrid functional Petri net (HFPN) was developed especially for biological modeling in order to provide biologists with a more intuitive Petri net-based method. In the literature, HFPNs are used to represent kinetic models at the molecular level. We present two models of long-term potentiation previously represented by differential equations which we have transformed into HFPN models: a phenomenological synapse model and a molecular-level model of the CaMKII regulation pathway. Through simulation, we obtained results similar to those of previous studies using these models. Our results open the way to a new type of modeling for systems biology where HFPNs are used to combine different levels of abstraction within one model. This approach can be useful in fully modeling a system at the molecular level when kinetic data is missing or when a full study of a system at the molecular level it is not within the scope of the research.

Bond-valence methods for pKa prediction. II. Bond-valence, electrostatic, molecular geometry, and solvation effects

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

Bickmore, Barry R.; Rosso, Kevin M.; Tadanier, Christopher J.

2006-08-15

In a previous contribution, we outlined a method for predicting (hydr)oxy-acid and oxide surface acidity constants based on three main factors: bond valence, Me?O bond ionicity, and molecular shape. Here electrostatics calculations and ab initio molecular dynamics simulations are used to qualitatively show that Me?O bond ionicity controls the extent to which the electrostatic work of proton removal departs from ideality, bond valence controls the extent of solvation of individual functional groups, and bond valence and molecular shape controls local dielectric response. These results are consistent with our model of acidity, but completely at odds with other methods of predictingmore » acidity constants for use in multisite complexation models. In particular, our ab initio molecular dynamics simulations of solvated monomers clearly indicate that hydrogen bonding between (hydr)oxo-groups and water molecules adjusts to obey the valence sum rule, rather than maintaining a fixed valence based on the coordination of the oxygen atom as predicted by the standard MUSIC model.« less

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.

Hydration of Li+ -ion in atom-bond electronegativity equalization method-7P water: a molecular dynamics simulation study.

PubMed

Li, Xin; Yang, Zhong-Zhi

2005-02-22

We have carried out molecular dynamics simulations of a Li(+) ion in water over a wide range of temperature (from 248 to 368 K). The simulations make use of the atom-bond electronegativity equalization method-7P water model, a seven-site flexible model with fluctuating charges, which has accurately reproduced many bulk water properties. The recently constructed Li(+)-water interaction potential through fitting to the experimental and ab initio gas-phase binding energies and to the measured structures for Li(+)-water clusters is adopted in the simulations. ABEEM was proposed and developed in terms of partitioning the electron density into atom and bond regions and using the electronegativity equalization method (EEM) and the density functional theory (DFT). Based on a combination of the atom-bond electronegativity equalization method and molecular mechanics (ABEEM/MM), a new set of water-water and Li(+)-water potentials, successfully applied to ionic clusters Li(+)(H(2)O)(n)(n=1-6,8), are further investigated in an aqueous solution of Li(+) in the present paper. Two points must be emphasized in the simulations: first, the model allows for the charges on the interacting sites fluctuating as a function of time; second, the ABEEM-7P model has applied the parameter k(lp,H)(R(lp,H)) to explicitly describe the short-range interaction of hydrogen bond in the hydrogen bond interaction region, and has a new description for the hydrogen bond. The static, dynamic, and thermodynamic properties have been studied in detail. In addition, at different temperatures, the structural properties such as radial distribution functions, and the dynamical properties such as diffusion coefficients and residence times of the water molecules in the first hydration shell of Li(+), are also simulated well. These simulation results show that the ABEEM/MM-based water-water and Li(+)-water potentials appear to be robust giving the overall characteristic hydration properties in excellent agreement with experiments and other molecular dynamics simulations on similar system.

Dynamic Structure of a Molecular Liquid S0.5Cl0.5: Ab initio Molecular-Dynamics Simulations

NASA Astrophysics Data System (ADS)

Ohmura, Satoshi; Shimakura, Hironori; Kawakita, Yukinobu; Shimojo, Fuyuki; Yao, Makoto

2013-07-01

The static and dynamic structures of a molecular liquid S0.5Cl0.5 consisting of Cl--S--S--Cl (S2Cl2) type molecules are studied by means of ab initio molecular dynamics simulations. Both the calculated static and dynamic structure factors are in good agreement with experimental results. The dynamic structures are discussed based on van-Hove distinct correlation functions, molecular translational mean-square displacements (TMSD) and rotational mean-square displacements (RMSD). In the TMSD and RMSD, there are ballistic and diffusive regimes in the sub-picosecond and picosecond time regions, respectively. These time scales are consistent with the decay time observed experimentally. The interaction between molecules in the liquid is also discussed in comparison with that in another liquid chalcogen--halogen system Se0.5Cl0.5.

A low Earth orbit molecular beam space simulation facility

NASA Technical Reports Server (NTRS)

Cross, J. B.

1984-01-01

A brief synopsis of the low Earth orbit (LEO) satellite environment is presented including neutral and ionic species. Two ground based atomic and molecular beam instruments are described which are capable of simulating the interaction of spacecraft surfaces with the LEO environment and detecting the results of these interactions. The first detects mass spectrometrically low level fluxes of reactively and nonreactively surface scattered species as a function of scattering angle and velocity while the second ultrahigh velocity (UHV) molecular beam, laser induced fluorescence apparatus is capable of measuring chemiluminescence produced by either gas phase or gas-surface interactions. A number of proposed experiments are described.

Energy Storage Analysis of a Mixed R161/MOF-5 Nanoparticle Nanofluid Based on Molecular Simulations

PubMed Central

Wang, Qiang; Tang, Shengli; Li, Leilei

2018-01-01

The thermal properties of refrigerants can be modified by adding porous nanoparticles into them. Here, molecular simulations, including molecular dynamics and grand canonical Monte Carlo, were employed to study the thermal energy storage properties of an R161/MOF-5 nanofluid. The results show that the thermodynamic energy change of MOF-5 nanoparticles is linear to the temperature. The adsorption heat calculated by grand canonical Monte Carlo is close to that calculated by the Clausius–Clapeyron equation. Additionally, a negative enhancement of the thermal energy storage capacity of the R161/MOF-5 nanofluid is found near the phase transition area. PMID:29783773

Energy Storage Analysis of a Mixed R161/MOF-5 Nanoparticle Nanofluid Based on Molecular Simulations.

PubMed

Wang, Qiang; Tang, Shengli; Li, Leilei

2018-05-20

The thermal properties of refrigerants can be modified by adding porous nanoparticles into them. Here, molecular simulations, including molecular dynamics and grand canonical Monte Carlo, were employed to study the thermal energy storage properties of an R161/MOF-5 nanofluid. The results show that the thermodynamic energy change of MOF-5 nanoparticles is linear to the temperature. The adsorption heat calculated by grand canonical Monte Carlo is close to that calculated by the Clausius⁻Clapeyron equation. Additionally, a negative enhancement of the thermal energy storage capacity of the R161/MOF-5 nanofluid is found near the phase transition area.

QMMMW: A wrapper for QM/MM simulations with QUANTUM ESPRESSO and LAMMPS

NASA Astrophysics Data System (ADS)

Ma, Changru; Martin-Samos, Layla; Fabris, Stefano; Laio, Alessandro; Piccinin, Simone

2015-10-01

We present QMMMW, a new program aimed at performing Quantum Mechanics/Molecular Mechanics (QM/MM) molecular dynamics. The package operates as a wrapper that patches PWscf code included in the QUANTUM ESPRESSO distribution and LAMMPS Molecular Dynamics Simulator. It is designed with a paradigm based on three guidelines: (i) minimal amount of modifications on the parent codes, (ii) flexibility and computational efficiency of the communication layer and (iii) accuracy of the Hamiltonian describing the interaction between the QM and MM subsystems. These three features are seldom present simultaneously in other implementations of QMMM. The QMMMW project is hosted by qe-forge at

Carbonic anhydrase inhibition of Schiff base derivative of imino-methyl-naphthalen-2-ol: Synthesis, structure elucidation, molecular docking, dynamic simulation and density functional theory calculations

NASA Astrophysics Data System (ADS)

Abbas, Saghir; Nasir, Hafiza Huma; Zaib, Sumera; Ali, Saqib; Mahmood, Tariq; Ayub, Khurshid; Tahir, Muhammad Nawaz; Iqbal, Jamshed

2018-03-01

In the present study, we have designed and synthesized a Schiff base derivative 3 and characterized by FT-IR, 1H and 13C NMR spectroscopy. Single crystal X-ray diffraction and NMR studies were also performed. The synthetic compound was screened for its inhibitory potential against carbonic anhydrase II. The experimental results were validated by molecular docking and dynamic simulations of compound 3 in the active pocket of enzyme. Important binding interactions with the key residues in the active site of the carbonic anhydrase enzyme were revealed. Moreover, supramolecular assembly of the title compound was analyzed by density functional theory (DFT) calculations. These studies rendered a more clear understanding for the demonstration of novel molecular mechanism involved in CA II inhibition by the synthesized compound.

Single-molecule quantum dot as a Kondo simulator

NASA Astrophysics Data System (ADS)

Hiraoka, R.; Minamitani, E.; Arafune, R.; Tsukahara, N.; Watanabe, S.; Kawai, M.; Takagi, N.

2017-06-01

Structural flexibility of molecule-based systems is key to realizing the novel functionalities. Tuning the structure in the atomic scale enables us to manipulate the quantum state in the molecule-based system. Here we present the reversible Hamiltonian manipulation in a single-molecule quantum dot consisting of an iron phthalocyanine molecule attached to an Au electrode and a scanning tunnelling microscope tip. We precisely controlled the position of Fe2+ ion in the molecular cage by using the tip, and tuned the Kondo coupling between the molecular spins and the Au electrode. Then, we realized the crossover between the strong-coupling Kondo regime and the weak-coupling regime governed by spin-orbit interaction in the molecule. The results open an avenue to simulate low-energy quantum many-body physics and quantum phase transition through the molecular flexibility.

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.

Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD4 inhibitors.

PubMed

Yan, Guoyi; Hou, Manzhou; Luo, Jiang; Pu, Chunlan; Hou, Xueyan; Lan, Suke; Li, Rui

2018-02-01

Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC 50 values against human cancer cell lines MV4-11, A375, and HeLa were 4.2, 7.1, and 11.6 μm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound-healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5. © 2017 John Wiley & Sons A/S.

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

PubMed

Chan, Eric J; Neumann, Marcus A

2018-04-10

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

Graphene symmetry-breaking with molecular adsorbates: modeling and experiment

NASA Astrophysics Data System (ADS)

Groce, M. A.; Hawkins, M. K.; Wang, Y. L.; Cullen, W. G.; Einstein, T. L.

2012-02-01

Graphene's structure and electronic properties provide a framework for understanding molecule-substrate interactions and developing techniques for band gap engineering. Controlled deposition of molecular adsorbates can create superlattices which break the degeneracy of graphene's two-atom unit cell, opening a band gap. We simulate scanning tunneling microscopy and spectroscopy measurements for a variety of organic molecule/graphene systems, including pyridine, trimesic acid, and isonicotinic acid, based on density functional theory calculations using VASP. We also compare our simulations to ultra-high vacuum STM and STS results.

Local structure in anisotropic systems determined by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Komolkin, Andrei V.; Maliniak, Arnold

In the present communication we describe the investigation of local structure using a new visualization technique. The approach is based on two-dimensional pair correlation functions derived from a molecular dynamics computer simulation. We have used this method to analyse a trajectory produced in a simulation of a nematic liquid crystal of 4-n-pentyl-4'-cyanobiphenyl (5CB) (Komolkin et al., 1994, J. chem. Phys., 101, 4103). The molecule is assumed to have cylindrical symmetry, and the liquid crystalline phase is treated as uniaxial. The pair correlation functions or cylindrical distribution functions (CDFs) are calculated in the molecular (m) and laboratory (l) frames, gm2(z1 2, d1 2) and g12(Z1 2, D1 2). Anisotropic molecular organization in the liquid crystal is reflected in laboratory frame CDFs. The molecular excluded volume is determined and the effect of the fast motion in the alkyl chain is observed. The intramolecular distributions are included in the CDFs and indicate the size of the motional amplitude in the chain. Absence of long range order was confirmed, a feature typical for a nematic liquid crystal.

Structure, Kinetics, and Thermodynamics of the Aqueous Uranyl(VI) Cation

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

Kerisit, Sebastien N.; Liu, Chongxuan

2013-08-20

Molecular simulation techniques are employed to gain insights into the structural, kinetic, and thermodynamic properties of the uranyl(VI) cation (UO22+) in aqueous solution. The simulations make use of an atomistic potential model (force field) derived in this work and based on the model of Guilbaud and Wipff (Guilbaud, P.; Wipff, G. J. Mol. Struct. (THEOCHEM) 1996, 366, 55-63). Reactive flux and thermodynamic integration calculations show that the derived potential model yields predictions for the water exchange rate and free energy of hydration, respectively, that are in agreement with experimental data. The water binding energies, hydration shell structure, and self-diffusion coefficientmore » are also calculated and discussed. Finally, a combination of metadynamics and transition path sampling simulations is employed to probe the mechanisms of water exchange reactions in the first hydration shell of the uranyl ion. These atomistic simulations indicate, based on two-dimensional free energy surfaces, that water exchanges follow an associative interchange mechanism. The nature and structure of the water exchange transition states are also determined. The improved potential model is expected to lead to more accurate predictions of uranyl adsorption energies at mineral surfaces using potential-based molecular dynamics simulations.« less

Accuracy of buffered-force QM/MM simulations of silica

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

Peguiron, Anke; Moras, Gianpietro; Colombi Ciacchi, Lucio

2015-02-14

We report comparisons between energy-based quantum mechanics/molecular mechanics (QM/MM) and buffered force-based QM/MM simulations in silica. Local quantities—such as density of states, charges, forces, and geometries—calculated with both QM/MM approaches are compared to the results of full QM simulations. We find the length scale over which forces computed using a finite QM region converge to reference values obtained in full quantum-mechanical calculations is ∼10 Å rather than the ∼5 Å previously reported for covalent materials such as silicon. Electrostatic embedding of the QM region in the surrounding classical point charges gives only a minor contribution to the force convergence. Whilemore » the energy-based approach provides accurate results in geometry optimizations of point defects, we find that the removal of large force errors at the QM/MM boundary provided by the buffered force-based scheme is necessary for accurate constrained geometry optimizations where Si–O bonds are elongated and for finite-temperature molecular dynamics simulations of crack propagation. Moreover, the buffered approach allows for more flexibility, since special-purpose QM/MM coupling terms that link QM and MM atoms are not required and the region that is treated at the QM level can be adaptively redefined during the course of a dynamical simulation.« less

Hybrid molecular dynamics simulation for plasma induced damage analysis

NASA Astrophysics Data System (ADS)

Matsukuma, Masaaki

2016-09-01

In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam experiments. This observed damage profile dependence on species and substrate cannot be reproduced using classical MD simulations. While the Moliere potential is convenient to describe the interactions between halogens and other atoms, more accurate interatomic modeling such as DFTB method which takes the molecular orbitals into account should be utilized to make the simulations more realistic. Based on the simulations results, the damage formation scenario will be discussed.

Convergence and reproducibility in molecular dynamics simulations of the DNA duplex d(GCACGAACGAACGAACGC)

PubMed Central

Galindo-Murillo, Rodrigo; Roe, Daniel R.; Cheatham, Thomas E.

2014-01-01

Background The structure and dynamics of DNA are critically related to its function. Molecular dynamics (MD) simulations augment experiment by providing detailed information about the atomic motions. However, to date the simulations have not been long enough for convergence of the dynamics and structural properties of DNA. Methods MD simulations performed with AMBER using the ff99SB force field with the parmbsc0 modifications, including ensembles of independent simulations, were compared to long timescale MD performed with the specialized Anton MD engine on the B-DNA structure d(GCACGAACGAACGAACGC). To assess convergence, the decay of the average RMSD values over longer and longer time intervals was evaluated in addition to assessing convergence of the dynamics via the Kullback-Leibler divergence of principal component projection histograms. Results These MD simulations —including one of the longest simulations of DNA published to date at ~44 μs—surprisingly suggest that the structure and dynamics of the DNA helix, neglecting the terminal base pairs, are essentially fully converged on the ~1–5 μs timescale. Conclusions We can now reproducibly converge the structure and dynamics of B-DNA helices, omitting the terminal base pairs, on the μs time scale with both the AMBER and CHARMM C36 nucleic acid force fields. Results from independent ensembles of simulations starting from different initial conditions, when aggregated, match the results from long timescale simulations on the specialized Anton MD engine. General Significance With access to large-scale GPU resources or the specialized MD engine “Anton” it is possibly for a variety of molecular systems to reproducibly and reliably converge the conformational ensemble of sampled structures. PMID:25219455

GENESIS: a hybrid-parallel and multi-scale molecular dynamics simulator with enhanced sampling algorithms for biomolecular and cellular simulations

PubMed Central

Jung, Jaewoon; Mori, Takaharu; Kobayashi, Chigusa; Matsunaga, Yasuhiro; Yoda, Takao; Feig, Michael; Sugita, Yuji

2015-01-01

GENESIS (Generalized-Ensemble Simulation System) is a new software package for molecular dynamics (MD) simulations of macromolecules. It has two MD simulators, called ATDYN and SPDYN. ATDYN is parallelized based on an atomic decomposition algorithm for the simulations of all-atom force-field models as well as coarse-grained Go-like models. SPDYN is highly parallelized based on a domain decomposition scheme, allowing large-scale MD simulations on supercomputers. Hybrid schemes combining OpenMP and MPI are used in both simulators to target modern multicore computer architectures. Key advantages of GENESIS are (1) the highly parallel performance of SPDYN for very large biological systems consisting of more than one million atoms and (2) the availability of various REMD algorithms (T-REMD, REUS, multi-dimensional REMD for both all-atom and Go-like models under the NVT, NPT, NPAT, and NPγT ensembles). The former is achieved by a combination of the midpoint cell method and the efficient three-dimensional Fast Fourier Transform algorithm, where the domain decomposition space is shared in real-space and reciprocal-space calculations. Other features in SPDYN, such as avoiding concurrent memory access, reducing communication times, and usage of parallel input/output files, also contribute to the performance. We show the REMD simulation results of a mixed (POPC/DMPC) lipid bilayer as a real application using GENESIS. GENESIS is released as free software under the GPLv2 licence and can be easily modified for the development of new algorithms and molecular models. WIREs Comput Mol Sci 2015, 5:310–323. doi: 10.1002/wcms.1220 PMID:26753008

Long range Debye-Hückel correction for computation of grid-based electrostatic forces between biomacromolecules

PubMed Central

2014-01-01

Background Brownian dynamics (BD) simulations can be used to study very large molecular systems, such as models of the intracellular environment, using atomic-detail structures. Such simulations require strategies to contain the computational costs, especially for the computation of interaction forces and energies. A common approach is to compute interaction forces between macromolecules by precomputing their interaction potentials on three-dimensional discretized grids. For long-range interactions, such as electrostatics, grid-based methods are subject to finite size errors. We describe here the implementation of a Debye-Hückel correction to the grid-based electrostatic potential used in the SDA BD simulation software that was applied to simulate solutions of bovine serum albumin and of hen egg white lysozyme. Results We found that the inclusion of the long-range electrostatic correction increased the accuracy of both the protein-protein interaction profiles and the protein diffusion coefficients at low ionic strength. Conclusions An advantage of this method is the low additional computational cost required to treat long-range electrostatic interactions in large biomacromolecular systems. Moreover, the implementation described here for BD simulations of protein solutions can also be applied in implicit solvent molecular dynamics simulations that make use of gridded interaction potentials. PMID:25045516

Study of Nanocomposites of Amino Acids and Organic Polyethers by Means of Mass Spectrometry and Molecular Dynamics Simulation

NASA Astrophysics Data System (ADS)

Zobnina, V. G.; Kosevich, M. V.; Chagovets, V. V.; Boryak, O. A.

A problem of elucidation of structure of nanomaterials based on combination of proteins and polyether polymers is addressed on the monomeric level of single amino acids and oligomers of PEG-400 and OEG-5 polyethers. Efficiency of application of combined approach involving experimental electrospray mass spectrometry and computer modeling by molecular dynamics simulation is demonstrated. It is shown that oligomers of polyethers form stable complexes with amino acids valine, proline, histidine, glutamic, and aspartic acids. Molecular dynamics simulation has shown that stabilization of amino acid-polyether complexes is achieved due to winding of the polymeric chain around charged groups of amino acids. Structural motives revealed for complexes of single amino acids with polyethers can be realized in structures of protein-polyether nanoparticles currently designed for drug delivery.

Application of molecular dynamics simulation to predict the compatability between water-insoluble drugs and self-associating poly(ethylene oxide)-b-poly(epsilon-caprolactone) block copolymers.

PubMed

Patel, Sarthak; Lavasanifar, Afsaneh; Choi, Phillip

2008-11-01

In the present work, molecular dynamics (MD) simulation was applied to study the solubility of two water-insoluble drugs, fenofibrate and nimodipine, in a series of micelle-forming PEO-b-PCL block copolymers with combinations of blocks having different molecular weights. The solubility predictions based on the MD results were then compared with those obtained from solubility experiments and by the commonly used group contribution method (GCM). The results showed that Flory-Huggins interaction parameters computed by the MD simulations are consistent with the solubility data of the drug/PEO-b-PCL systems, whereas those calculated by the GCM significantly deviate from the experimental observation. We have also accounted for the possibility of drug solubilization in the PEO block of PEO-b-PCL.

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics.

PubMed

Martínez, Enrique; Cawkwell, Marc J; Voter, Arthur F; Niklasson, Anders M N

2015-04-21

Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached at each time step. The thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.

Communication: Quantum molecular dynamics simulation of liquid para-hydrogen by nuclear and electron wave packet approach.

PubMed

Hyeon-Deuk, Kim; Ando, Koji

2014-05-07

Liquid para-hydrogen (p-H2) is a typical quantum liquid which exhibits strong nuclear quantum effects (NQEs) and thus anomalous static and dynamic properties. We propose a real-time simulation method of wave packet (WP) molecular dynamics (MD) based on non-empirical intra- and inter-molecular interactions of non-spherical hydrogen molecules, and apply it to condensed-phase p-H2. The NQEs, such as WP delocalization and zero-point energy, are taken into account without perturbative expansion of prepared model potential functions but with explicit interactions between nuclear and electron WPs. The developed MD simulation for 100 ps with 1200 hydrogen molecules is realized at feasible computational cost, by which basic experimental properties of p-H2 liquid such as radial distribution functions, self-diffusion coefficients, and shear viscosities are all well reproduced.

Electric Double-Layer Structure in Primitive Model Electrolytes. Comparing Molecular Dynamics with Local-Density Approximations

DOE PAGES

Giera, Brian; Lawrence Livermore National Lab.; Henson, Neil; ...

2015-02-27

We evaluate the accuracy of local-density approximations (LDAs) using explicit molecular dynamics simulations of binary electrolytes comprised of equisized ions in an implicit solvent. The Bikerman LDA, which considers ions to occupy a lattice, poorly captures excluded volume interactions between primitive model ions. Instead, LDAs based on the Carnahan–Starling (CS) hard-sphere equation of state capture simulated values of ideal and excess chemical potential profiles extremely well, as is the relationship between surface charge density and electrostatic potential. Excellent agreement between the EDL capacitances predicted by CS-LDAs and computed in molecular simulations is found even in systems where ion correlations drivemore » strong density and free charge oscillations within the EDL, despite the inability of LDAs to capture the oscillations in the detailed EDL profiles.« less

A model for self-diffusion of guanidinium-based ionic liquids: a molecular simulation study.

PubMed

Klähn, Marco; Seduraman, Abirami; Wu, Ping

2008-11-06

We propose a novel self-diffusion model for ionic liquids on an atomic level of detail. The model is derived from molecular dynamics simulations of guanidinium-based ionic liquids (GILs) as a model case. The simulations are based on an empirical molecular mechanical force field, which has been developed in our preceding work, and it relies on the charge distribution in the actual liquid. The simulated GILs consist of acyclic and cyclic cations that were paired with nitrate and perchlorate anions. Self-diffusion coefficients are calculated at different temperatures from which diffusive activation energies between 32-40 kJ/mol are derived. Vaporization enthalpies between 174-212 kJ/mol are calculated, and their strong connection with diffusive activation energies is demonstrated. An observed formation of cavities in GILs of up to 6.5% of the total volume does not facilitate self-diffusion. Instead, the diffusion of ions is found to be determined primarily by interactions with their immediate environment via electrostatic attraction between cation hydrogen and anion oxygen atoms. The calculated average time between single diffusive transitions varies between 58-107 ps and determines the speed of diffusion, in contrast to diffusive displacement distances, which were found to be similar in all simulated GILs. All simulations indicate that ions diffuse by using a brachiation type of movement: a diffusive transition is initiated by cleaving close contacts to a coordinated counterion, after which the ion diffuses only about 2 A until new close contacts are formed with another counterion in its vicinity. The proposed diffusion model links all calculated energetic and dynamic properties of GILs consistently and explains their molecular origin. The validity of the model is confirmed by providing an explanation for the variation of measured ratios of self-diffusion coefficients of cations and paired anions over a wide range of values, encompassing various ionic liquid classes as well as the simulated GILs. The proposed diffusion model facilitates the qualitative a priori prediction of the impact of ion modifications on the diffusive characteristics of new ionic liquids.

Using simulation to interpret experimental data in terms of protein conformational ensembles.

PubMed

Allison, Jane R

2017-04-01

In their biological environment, proteins are dynamic molecules, necessitating an ensemble structural description. Molecular dynamics simulations and solution-state experiments provide complimentary information in the form of atomically detailed coordinates and averaged or distributions of structural properties or related quantities. Recently, increases in the temporal and spatial scale of conformational sampling and comparison of the more diverse conformational ensembles thus generated have revealed the importance of sampling rare events. Excitingly, new methods based on maximum entropy and Bayesian inference are promising to provide a statistically sound mechanism for combining experimental data with molecular dynamics simulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular simulation of disjoining-pressure isotherms for free liquid , Lennard-Jones thin films

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

Bhatt, Divesh; Newman, John; Radke, C.J.

2001-10-01

We present canonical-ensemble molecular-dynamics simulations of disjoining-pressure isotherms in Lennard-Jones free liquid films. Thermodynamics demands that the disjoining pressure is determined uniquely as a function of the chemical potential purely from the phase diagram of the fluid. Our results from molecular dynamics validate this argument. The inverse-sixth-power distance term in the Lennard-Jones intermolecular potential represents van der Waals dispersion forces. Hence, we compare our results with classical Hamaker theory that is based on dispersion forces but assumes a slab geometry for the density profile and completely neglects fluid structure and entropy. We find that the Hamaker constant obtained from ourmore » simulations is about an order of magnitude larger than that from classical theory. To investigate the origin of this discrepancy, we calculate the disjoining-pressure isotherm using a density-functional theory relaxing the inherent assumptions in the Hamaker theory and imparting to the fluid an approximate structure. For disjoining pressure as a function of chemical potential, the results of density-functional theory and molecular dynamics are very close. Even for disjoining-pressure isotherms, and the subsequently calculated Hamaker constant, results of the density-functional theory are closer to the molecular-dynamics simulations by about a factor of 4 compared to Hamaker theory. [References: 44]« less

Molecular docking and molecular dynamics simulation analyses of urea with ammoniated and ammoxidized lignin.

PubMed

Li, Wenzhuo; Zhang, Song; Zhao, Yingying; Huang, Shuaiyu; Zhao, Jiangshan

2017-01-01

Ammoniated lignin, prepared through the Mannich reaction of lignin, has more advantages as a slow-release carrier of urea molecules than ammoxidized lignin and lignin. The advantages of the ammoniated lignin include its amine groups added and its high molecular mass kept as similar as that of lignin. Three organic molecules including guaiacyl, 2-hydroxybenzylamine and 5-carbamoylpentanoic acid are monomers respectively in lignin, ammoniated lignin and ammoxidized lignin. We studied the difference between the interactions of lignin, ammoniated lignin and ammoxidized lignin with respect to urea, based on radial distribution functions (RDFs) results from molecular dynamics (MD) simulations. Glass transition temperature (T g ) and solubility parameter (δ) of ammoniated and ammoxidized lignin have been calculated by MD simulations in the constant-temperature and constant-pressure ensemble (NPT). Molecular docking results showed the interaction sites of the urea onto the ammoniated and ammoxidized lignin and three different interaction modes were identified. Root mean square deviation (RMSD) values could indicate the mobilities of the urea molecule affected by the three different interaction modes. A series of MD simulations in the constant-temperature and constant-volume ensemble (NVT) helped us to calculate the diffusivity of urea which was affected by the content of urea in ammoniated and ammoxidized lignin. Copyright © 2016 Elsevier Inc. All rights reserved.

A multilevel-skin neighbor list algorithm for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Zhang, Chenglong; Zhao, Mingcan; Hou, Chaofeng; Ge, Wei

2018-01-01

Searching of the interaction pairs and organization of the interaction processes are important steps in molecular dynamics (MD) algorithms and are critical to the overall efficiency of the simulation. Neighbor lists are widely used for these steps, where thicker skin can reduce the frequency of list updating but is discounted by more computation in distance check for the particle pairs. In this paper, we propose a new neighbor-list-based algorithm with a precisely designed multilevel skin which can reduce unnecessary computation on inter-particle distances. The performance advantages over traditional methods are then analyzed against the main simulation parameters on Intel CPUs and MICs (many integrated cores), and are clearly demonstrated. The algorithm can be generalized for various discrete simulations using neighbor lists.

Conformational equilibria of alkanes in aqueous solution: relationship to water structure near hydrophobic solutes.

PubMed Central

Ashbaugh, H S; Garde, S; Hummer, G; Kaler, E W; Paulaitis, M E

1999-01-01

Conformational free energies of butane, pentane, and hexane in water are calculated from molecular simulations with explicit waters and from a simple molecular theory in which the local hydration structure is estimated based on a proximity approximation. This proximity approximation uses only the two nearest carbon atoms on the alkane to predict the local water density at a given point in space. Conformational free energies of hydration are subsequently calculated using a free energy perturbation method. Quantitative agreement is found between the free energies obtained from simulations and theory. Moreover, free energy calculations using this proximity approximation are approximately four orders of magnitude faster than those based on explicit water simulations. Our results demonstrate the accuracy and utility of the proximity approximation for predicting water structure as the basis for a quantitative description of n-alkane conformational equilibria in water. In addition, the proximity approximation provides a molecular foundation for extending predictions of water structure and hydration thermodynamic properties of simple hydrophobic solutes to larger clusters or assemblies of hydrophobic solutes. PMID:10423414

Capturing RNA Folding Free Energy with Coarse-Grained Molecular Dynamics Simulations

PubMed Central

Bell, David R.; Cheng, Sara Y.; Salazar, Heber; Ren, Pengyu

2017-01-01

We introduce a coarse-grained RNA model for molecular dynamics simulations, RACER (RnA CoarsE-gRained). RACER achieves accurate native structure prediction for a number of RNAs (average RMSD of 2.93 Å) and the sequence-specific variation of free energy is in excellent agreement with experimentally measured stabilities (R2 = 0.93). Using RACER, we identified hydrogen-bonding (or base pairing), base stacking, and electrostatic interactions as essential driving forces for RNA folding. Also, we found that separating pairing vs. stacking interactions allowed RACER to distinguish folded vs. unfolded states. In RACER, base pairing and stacking interactions each provide an approximate stability of 3–4 kcal/mol for an A-form helix. RACER was developed based on PDB structural statistics and experimental thermodynamic data. In contrast with previous work, RACER implements a novel effective vdW potential energy function, which led us to re-parameterize hydrogen bond and electrostatic potential energy functions. Further, RACER is validated and optimized using a simulated annealing protocol to generate potential energy vs. RMSD landscapes. Finally, RACER is tested using extensive equilibrium pulling simulations (0.86 ms total) on eleven RNA sequences (hairpins and duplexes). PMID:28393861

Multiscale QM/MM molecular dynamics study on the first steps of guanine damage by free hydroxyl radicals in solution.

PubMed

Abolfath, Ramin M; Biswas, P K; Rajnarayanam, R; Brabec, Thomas; Kodym, Reinhard; Papiez, Lech

2012-04-19

Understanding the damage of DNA bases from hydrogen abstraction by free OH radicals is of particular importance to understanding the indirect effect of ionizing radiation. Previous studies address the problem with truncated DNA bases as ab initio quantum simulations required to study such electronic-spin-dependent processes are computationally expensive. Here, for the first time, we employ a multiscale and hybrid quantum mechanical-molecular mechanical simulation to study the interaction of OH radicals with a guanine-deoxyribose-phosphate DNA molecular unit in the presence of water, where all of the water molecules and the deoxyribose-phosphate fragment are treated with the simplistic classical molecular mechanical scheme. Our result illustrates that the presence of water strongly alters the hydrogen-abstraction reaction as the hydrogen bonding of OH radicals with water restricts the relative orientation of the OH radicals with respect to the DNA base (here, guanine). This results in an angular anisotropy in the chemical pathway and a lower efficiency in the hydrogen-abstraction mechanisms than previously anticipated for identical systems in vacuum. The method can easily be extended to single- and double-stranded DNA without any appreciable computational cost as these molecular units can be treated in the classical subsystem, as has been demonstrated here. © 2012 American Chemical Society

Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.

PubMed

Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard

2017-04-07

Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular dynamics simulation study of the early stages of nucleation of iron oxyhydroxide nanoparticles in aqueous solutions

DOE PAGES

Zhang, Hengzhong; Waychunas, Glenn A.; Banfield, Jillian F.

2015-07-29

Nucleation is a fundamental step in crystal growth. Of environmental and materials relevance are reactions that lead to nucleation of iron oxyhydroxides in aqueous solutions. These reactions are difficult to study experimentally due to their rapid kinetics. Here, we used classical molecular dynamics simulations to investigate nucleation of iron hydroxide/oxyhydroxide nanoparticles in aqueous solutions. Results show that in a solution containing ferric ions and hydroxyl groups, iron–hydroxyl molecular clusters form by merging ferric monomers, dimers, and other oligomers, driven by strong affinity of ferric ions to hydroxyls. When deprotonation reactions are not considered in the simulations, these clusters aggregate tomore » form small iron hydroxide nanocrystals with a six-membered ring-like layered structure allomeric to gibbsite. By comparison, in a solution containing iron chloride and sodium hydroxide, the presence of chlorine drives cluster assembly along a different direction to form long molecular chains (rather than rings) composed of Fe–O octahedra linked by edge sharing. Further, in chlorine-free solutions, when deprotonation reactions are considered, the simulations predict ultimate formation of amorphous iron oxyhydroxide nanoparticles with local atomic structure similar to that of ferrihydrite nanoparticles. Overall, our simulation results reveal that nucleation of iron oxyhydroxide nanoparticles proceeds via a cluster aggregation-based nonclassical pathway.« less

Avoiding fractional electrons in subsystem DFT based ab-initio molecular dynamics yields accurate models for liquid water and solvated OH radical

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

Genova, Alessandro, E-mail: alessandro.genova@rutgers.edu; Pavanello, Michele, E-mail: m.pavanello@rutgers.edu; Ceresoli, Davide, E-mail: davide.ceresoli@cnr.it

2016-06-21

In this work we achieve three milestones: (1) we present a subsystem DFT method capable of running ab-initio molecular dynamics simulations accurately and efficiently. (2) In order to rid the simulations of inter-molecular self-interaction error, we exploit the ability of semilocal frozen density embedding formulation of subsystem DFT to represent the total electron density as a sum of localized subsystem electron densities that are constrained to integrate to a preset, constant number of electrons; the success of the method relies on the fact that employed semilocal nonadditive kinetic energy functionals effectively cancel out errors in semilocal exchange–correlation potentials that aremore » linked to static correlation effects and self-interaction. (3) We demonstrate this concept by simulating liquid water and solvated OH{sup •} radical. While the bulk of our simulations have been performed on a periodic box containing 64 independent water molecules for 52 ps, we also simulated a box containing 256 water molecules for 22 ps. The results show that, provided one employs an accurate nonadditive kinetic energy functional, the dynamics of liquid water and OH{sup •} radical are in semiquantitative agreement with experimental results or higher-level electronic structure calculations. Our assessments are based upon comparisons of radial and angular distribution functions as well as the diffusion coefficient of the liquid.« less

Avoiding fractional electrons in subsystem DFT based ab-initio molecular dynamics yields accurate models for liquid water and solvated OH radical.

PubMed

Genova, Alessandro; Ceresoli, Davide; Pavanello, Michele

2016-06-21

In this work we achieve three milestones: (1) we present a subsystem DFT method capable of running ab-initio molecular dynamics simulations accurately and efficiently. (2) In order to rid the simulations of inter-molecular self-interaction error, we exploit the ability of semilocal frozen density embedding formulation of subsystem DFT to represent the total electron density as a sum of localized subsystem electron densities that are constrained to integrate to a preset, constant number of electrons; the success of the method relies on the fact that employed semilocal nonadditive kinetic energy functionals effectively cancel out errors in semilocal exchange-correlation potentials that are linked to static correlation effects and self-interaction. (3) We demonstrate this concept by simulating liquid water and solvated OH(•) radical. While the bulk of our simulations have been performed on a periodic box containing 64 independent water molecules for 52 ps, we also simulated a box containing 256 water molecules for 22 ps. The results show that, provided one employs an accurate nonadditive kinetic energy functional, the dynamics of liquid water and OH(•) radical are in semiquantitative agreement with experimental results or higher-level electronic structure calculations. Our assessments are based upon comparisons of radial and angular distribution functions as well as the diffusion coefficient of the liquid.

Systematic Validation of Protein Force Fields against Experimental Data

PubMed Central

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

2012-01-01

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

Conformational Transition Pathways of Epidermal Growth Factor Receptor Kinase Domain from Multiple Molecular Dynamics Simulations and Bayesian Clustering.

PubMed

Li, Yan; Li, Xiang; Ma, Weiya; Dong, Zigang

2014-08-12

The epidermal growth factor receptor (EGFR) is aberrantly activated in various cancer cells and an important target for cancer treatment. Deep understanding of EGFR conformational changes between the active and inactive states is of pharmaceutical interest. Here we present a strategy combining multiply targeted molecular dynamics simulations, unbiased molecular dynamics simulations, and Bayesian clustering to investigate transition pathways during the activation/inactivation process of EGFR kinase domain. Two distinct pathways between the active and inactive forms are designed, explored, and compared. Based on Bayesian clustering and rough two-dimensional free energy surfaces, the energy-favorable pathway is recognized, though DFG-flip happens in both pathways. In addition, another pathway with different intermediate states appears in our simulations. Comparison of distinct pathways also indicates that disruption of the Lys745-Glu762 interaction is critically important in DFG-flip while movement of the A-loop significantly facilitates the conformational change. Our simulations yield new insights into EGFR conformational transitions. Moreover, our results verify that this approach is valid and efficient in sampling of protein conformational changes and comparison of distinct pathways.

Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations.

PubMed

Wu, Jie; Feng, Yu; Han, Chao; Huang, Wu; Shen, Zhibin; Yang, Mengdie; Chen, Weiqiang; Ye, Lianbao

2017-02-28

Germacrone is one of the major bioactive components in the Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria Roscoe, known as zedoary. The present study designed some novel germacrone derivatives based on combination principles, synthesized these compounds, and investigated their inhibitions on Bel-7402, HepG2, A549 and HeLa cells. Meanwhile, the study evaluated inhibitions of these derivatives on c-Met kinase, which has been detected in a number of cancers. The results suggested that the majority of the compounds showed stronger inhibitory effect on cancers and c-Met kinase than germacrone. Furthermore, our docking experiments analyzed the results and explained the molecular mechanism. Molecular dynamics simulations were then applied to perform further evaluation of the binding stabilities between compounds and their receptors.

Computer simulation of surface and film processes

NASA Technical Reports Server (NTRS)

Tiller, W. A.; Halicioglu, M. T.

1984-01-01

All the investigations which were performed employed in one way or another a computer simulation technique based on atomistic level considerations. In general, three types of simulation methods were used for modeling systems with discrete particles that interact via well defined potential functions: molecular dynamics (a general method for solving the classical equations of motion of a model system); Monte Carlo (the use of Markov chain ensemble averaging technique to model equilibrium properties of a system); and molecular statics (provides properties of a system at T = 0 K). The effects of three-body forces on the vibrational frequencies of triatomic cluster were investigated. The multilayer relaxation phenomena for low index planes of an fcc crystal was analyzed also as a function of the three-body interactions. Various surface properties for Si and SiC system were calculated. Results obtained from static simulation calculations for slip formation were presented. The more elaborate molecular dynamics calculations on the propagation of cracks in two-dimensional systems were outlined.

Molecular Dynamics Simulation Study of the Selectivity of a Silica Polymer for Ibuprofen

PubMed Central

Concu, Riccardo; Cordeiro, M. Natalia D. S.

2016-01-01

In the past few years, the sol-gel polycondensation technique has been increasingly employed with great success as an alternative approach to the preparation of molecularly imprinted materials (MIMs). The main aim of this study was to study, through a series of molecular dynamics (MD) simulations, the selectivity of an imprinted silica xerogel towards a new template—the (±)-2-(P-Isobutylphenyl) propionic acid (Ibuprofen, IBU). We have previously demonstrated the affinity of this silica xerogel toward a similar molecule. In the present study, we simulated the imprinting process occurring in a sol-gel mixture using the Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA) force field, in order to evaluate the selectivity of this xerogel for a template molecule. In addition, for the first time, we have developed and verified a new parameterisation for the Ibuprofen® based on the OPLS-AA framework. To evaluate the selectivity of the polymer, we have employed both the radial distribution functions, interaction energies and cluster analyses. PMID:27399685

Molecular Dynamics Simulation Study of the Selectivity of a Silica Polymer for Ibuprofen.

PubMed

Concu, Riccardo; Cordeiro, M Natalia D S

2016-07-07

In the past few years, the sol-gel polycondensation technique has been increasingly employed with great success as an alternative approach to the preparation of molecularly imprinted materials (MIMs). The main aim of this study was to study, through a series of molecular dynamics (MD) simulations, the selectivity of an imprinted silica xerogel towards a new template-the (±)-2-(P-Isobutylphenyl) propionic acid (Ibuprofen, IBU). We have previously demonstrated the affinity of this silica xerogel toward a similar molecule. In the present study, we simulated the imprinting process occurring in a sol-gel mixture using the Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA) force field, in order to evaluate the selectivity of this xerogel for a template molecule. In addition, for the first time, we have developed and verified a new parameterisation for the Ibuprofen(®) based on the OPLS-AA framework. To evaluate the selectivity of the polymer, we have employed both the radial distribution functions, interaction energies and cluster analyses.

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.

MDWiZ: a platform for the automated translation of molecular dynamics simulations.

PubMed

Rusu, Victor H; Horta, Vitor A C; Horta, Bruno A C; Lins, Roberto D; Baron, Riccardo

2014-03-01

A variety of popular molecular dynamics (MD) simulation packages were independently developed in the last decades to reach diverse scientific goals. However, such non-coordinated development of software, force fields, and analysis tools for molecular simulations gave rise to an array of software formats and arbitrary conventions for routine preparation and analysis of simulation input and output data. Different formats and/or parameter definitions are used at each stage of the modeling process despite largely contain redundant information between alternative software tools. Such Babel of languages that cannot be easily and univocally translated one into another poses one of the major technical obstacles to the preparation, translation, and comparison of molecular simulation data that users face on a daily basis. Here, we present the MDWiZ platform, a freely accessed online portal designed to aid the fast and reliable preparation and conversion of file formats that allows researchers to reproduce or generate data from MD simulations using different setups, including force fields and models with different underlying potential forms. The general structure of MDWiZ is presented, the features of version 1.0 are detailed, and an extensive validation based on GROMACS to LAMMPS conversion is presented. We believe that MDWiZ will be largely useful to the molecular dynamics community. Such fast format and force field exchange for a given system allows tailoring the chosen system to a given computer platform and/or taking advantage of a specific capabilities offered by different software engines. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Discrete diffusion models to study the effects of Mg2+ concentration on the PhoPQ signal transduction system

PubMed Central

2010-01-01

Background The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead. This objective motivates the use of new methods that can transform the problem from energy and affinity based modeling to information theory based modeling. To achieve this, we transform all dynamics within the cell into a random event time, which is specified through an information domain measure like probability distribution. This allows us to use the “in silico” stochastic event based modeling approach to find the molecular dynamics of the system. Results In this paper, we present the discrete event simulation concept using the example of the signal transduction cascade triggered by extra-cellular Mg2+ concentration in the two component PhoPQ regulatory system of Salmonella Typhimurium. We also present a model to compute the information domain measure of the molecular transport process by estimating the statistical parameters of inter-arrival time between molecules/ions coming to a cell receptor as external signal. This model transforms the diffusion process into the information theory measure of stochastic event completion time to get the distribution of the Mg2+ departure events. Using these molecular transport models, we next study the in-silico effects of this external trigger on the PhoPQ system. Conclusions Our results illustrate the accuracy of the proposed diffusion models in explaining the molecular/ionic transport processes inside the cell. Also, the proposed simulation framework can incorporate the stochasticity in cellular environments to a certain degree of accuracy. We expect that this scalable simulation platform will be able to model more complex biological systems with reasonable accuracy to understand their temporal dynamics. PMID:21143785

Discrete diffusion models to study the effects of Mg2+ concentration on the PhoPQ signal transduction system.

PubMed

Ghosh, Preetam; Ghosh, Samik; Basu, Kalyan; Das, Sajal K; Zhang, Chaoyang

2010-12-01

The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead. This objective motivates the use of new methods that can transform the problem from energy and affinity based modeling to information theory based modeling. To achieve this, we transform all dynamics within the cell into a random event time, which is specified through an information domain measure like probability distribution. This allows us to use the "in silico" stochastic event based modeling approach to find the molecular dynamics of the system. In this paper, we present the discrete event simulation concept using the example of the signal transduction cascade triggered by extra-cellular Mg2+ concentration in the two component PhoPQ regulatory system of Salmonella Typhimurium. We also present a model to compute the information domain measure of the molecular transport process by estimating the statistical parameters of inter-arrival time between molecules/ions coming to a cell receptor as external signal. This model transforms the diffusion process into the information theory measure of stochastic event completion time to get the distribution of the Mg2+ departure events. Using these molecular transport models, we next study the in-silico effects of this external trigger on the PhoPQ system. Our results illustrate the accuracy of the proposed diffusion models in explaining the molecular/ionic transport processes inside the cell. Also, the proposed simulation framework can incorporate the stochasticity in cellular environments to a certain degree of accuracy. We expect that this scalable simulation platform will be able to model more complex biological systems with reasonable accuracy to understand their temporal dynamics.

Misclassification Errors in Unsupervised Classification Methods. Comparison Based on the Simulation of Targeted Proteomics Data

PubMed Central

Andreev, Victor P; Gillespie, Brenda W; Helfand, Brian T; Merion, Robert M

2016-01-01

Unsupervised classification methods are gaining acceptance in omics studies of complex common diseases, which are often vaguely defined and are likely the collections of disease subtypes. Unsupervised classification based on the molecular signatures identified in omics studies have the potential to reflect molecular mechanisms of the subtypes of the disease and to lead to more targeted and successful interventions for the identified subtypes. Multiple classification algorithms exist but none is ideal for all types of data. Importantly, there are no established methods to estimate sample size in unsupervised classification (unlike power analysis in hypothesis testing). Therefore, we developed a simulation approach allowing comparison of misclassification errors and estimating the required sample size for a given effect size, number, and correlation matrix of the differentially abundant proteins in targeted proteomics studies. All the experiments were performed in silico. The simulated data imitated the expected one from the study of the plasma of patients with lower urinary tract dysfunction with the aptamer proteomics assay Somascan (SomaLogic Inc, Boulder, CO), which targeted 1129 proteins, including 330 involved in inflammation, 180 in stress response, 80 in aging, etc. Three popular clustering methods (hierarchical, k-means, and k-medoids) were compared. K-means clustering performed much better for the simulated data than the other two methods and enabled classification with misclassification error below 5% in the simulated cohort of 100 patients based on the molecular signatures of 40 differentially abundant proteins (effect size 1.5) from among the 1129-protein panel. PMID:27524871

Nanotechnology Review: Molecular Electronics to Molecular Motors

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Saini, Subhash (Technical Monitor)

1998-01-01

Reviewing the status of current approaches and future projections, as already published in scientific journals and books, the talk will summarize the direction in which computational and experimental nanotechnologies are progressing. Examples of nanotechnological approaches to the concepts of design and simulation of carbon nanotube based molecular electronic and mechanical devices will be presented. The concepts of nanotube based gears and motors will be discussed. The above is a non-technical review talk which covers long term precompetitive basic research in already published material that has been presented before many US scientific meeting audiences.

Electric potential calculation in molecular simulation of electric double layer capacitors

NASA Astrophysics Data System (ADS)

Wang, Zhenxing; Olmsted, David L.; Asta, Mark; Laird, Brian B.

2016-11-01

For the molecular simulation of electric double layer capacitors (EDLCs), a number of methods have been proposed and implemented to determine the one-dimensional electric potential profile between the two electrodes at a fixed potential difference. In this work, we compare several of these methods for a model LiClO4-acetonitrile/graphite EDLC simulated using both the traditional fixed-charged method (FCM), in which a fixed charge is assigned a priori to the electrode atoms, or the recently developed constant potential method (CPM) (2007 J. Chem. Phys. 126 084704), where the electrode charges are allowed to fluctuate to keep the potential fixed. Based on an analysis of the full three-dimensional electric potential field, we suggest a method for determining the averaged one-dimensional electric potential profile that can be applied to both the FCM and CPM simulations. Compared to traditional methods based on numerically solving the one-dimensional Poisson’s equation, this method yields better accuracy and no supplemental assumptions.

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.

Interaction of three new tetradentates Schiff bases containing N2O2 donor atoms with calf thymus DNA.

PubMed

Ajloo, Davood; Shabanpanah, Sajede; Shafaatian, Bita; Ghadamgahi, Maryam; Alipour, Yasin; Lashgarbolouki, Taghi; Saboury, Ali Akbar

2015-01-01

Interaction of 1,3-bis(2-hydroxy-benzylidene)-urea (H2L1), 1,3-bis(2-hydroxy-3-methoxy-benzylidene)-urea (H2L2) and 1,3-bis(2-hydroxy-3-methoxy-benzylidene)-urea nickel(II) (NiL2) with calf-thymus DNA were investigated by UV-vis absorption, fluorescence emission and circular dichroism (CD) spectroscopy as well as cyclic voltammetry, viscosity measurements, molecular docking and molecular dynamics simulation. Binding constants were determined using UV-vis absorption and fluorescence spectra. The results indicated that studied Schiff-bases bind to DNA in the intercalative mode in which the metal derivative is more effective than non metals. Their interaction trend is further determined by molecular dynamics (MD) simulation. MD results showed that Ni derivative reduces oligonucleotide intermolecular hydrogen bond and increases solvent accessible surface area more than other compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies.

PubMed

Soler, Miguel A; de Marco, Ario; Fortuna, Sara

2016-10-10

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies

NASA Astrophysics Data System (ADS)

Soler, Miguel A.; De Marco, Ario; Fortuna, Sara

2016-10-01

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

NMR spectroscopy and molecular modelling studies of nitrosylcobalamin: further evidence that the deprotonated, base-off form is important for nitrosylcobalamin in solution†

PubMed Central

Hassanin, Hanaa A.; Hannibal, Luciana; Jacobsen, Donald W.; Brown, Kenneth L.

2009-01-01

The structure of nitrosylcobalamin (NOCbl) in solution has been studied by NMR spectroscopy and the 1H and 13C NMR spectra have been assigned. 13C and 31P NMR chemical shifts, the UV-vis spectrum of NOCbl and the observed pK base-off value of ~5.1 for NOCbl provide evidence that a significant fraction of NOCbl is present in the base-off, 5,6-dimethylbenzimidazole (DMB) deprotonated, form in solution. NOE-restrained molecular mechanics modelling of base-on NOCbl gave annealed structures with minor conformational differences in the flexible side chains and the nucleotide loop position compared with the X-ray structure. A molecular dynamics simulation at 300 K showed that DMB remains in close proximity to the α face of the corrin in the base-off form of NOCbl. Simulated annealing calculations produced two major conformations of base-off NOCbl. In the first, the DMB is perpendicular to the corrin and its B3 nitrogen is about 3.1 Å away from and pointing directly at the metal ion; in the second the DMB is parallel to and tucked beneath the D ring of the corrin. PMID:19122899

Statistical inference on censored data for targeted clinical trials under enrichment design.

PubMed

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Tensile Strength of Carbon Nanotubes Under Realistic Temperature and Strain Rate

NASA Technical Reports Server (NTRS)

Wei, Chen-Yu; Cho, Kyeong-Jae; Srivastava, Deepak; Biegel, Bryan (Technical Monitor)

2002-01-01

Strain rate and temperature dependence of the tensile strength of single-wall carbon nanotubes has been investigated with molecular dynamics simulations. The tensile failure or yield strain is found to be strongly dependent on the temperature and strain rate. A transition state theory based predictive model is developed for the tensile failure of nanotubes. Based on the parameters fitted from high-strain rate and temperature dependent molecular dynamics simulations, the model predicts that a defect free micrometer long single-wall nanotube at 300 K, stretched with a strain rate of 1%/hour, fails at about 9 plus or minus 1% tensile strain. This is in good agreement with recent experimental findings.

Atomistic simulations of TeO₂-based glasses: interatomic potentials and molecular dynamics.

PubMed

Gulenko, Anastasia; Masson, Olivier; Berghout, Abid; Hamani, David; Thomas, Philippe

2014-07-21

In this work we present for the first time empirical interatomic potentials that are able to reproduce TeO2-based systems. Using these potentials in classical molecular dynamics simulations, we obtained first results for the pure TeO2 glass structure model. The calculated pair distribution function is in good agreement with the experimental one, which indicates a realistic glass structure model. We investigated the short- and medium-range TeO2 glass structures. The local environment of the Te atom strongly varies, so that the glass structure model has a broad Q polyhedral distribution. The glass network is described as weakly connected with a large number of terminal oxygen atoms.

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2015-01-01

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

Prediction of solubility parameters and miscibility of pharmaceutical compounds by molecular dynamics simulations.

PubMed

Gupta, Jasmine; Nunes, Cletus; Vyas, Shyam; Jonnalagadda, Sriramakamal

2011-03-10

The objectives of this study were (i) to develop a computational model based on molecular dynamics technique to predict the miscibility of indomethacin in carriers (polyethylene oxide, glucose, and sucrose) and (ii) to experimentally verify the in silico predictions by characterizing the drug-carrier mixtures using thermoanalytical techniques. Molecular dynamics (MD) simulations were performed using the COMPASS force field, and the cohesive energy density and the solubility parameters were determined for the model compounds. The magnitude of difference in the solubility parameters of drug and carrier is indicative of their miscibility. The MD simulations predicted indomethacin to be miscible with polyethylene oxide and to be borderline miscible with sucrose and immiscible with glucose. The solubility parameter values obtained using the MD simulations values were in reasonable agreement with those calculated using group contribution methods. Differential scanning calorimetry showed melting point depression of polyethylene oxide with increasing levels of indomethacin accompanied by peak broadening, confirming miscibility. In contrast, thermal analysis of blends of indomethacin with sucrose and glucose verified general immiscibility. The findings demonstrate that molecular modeling is a powerful technique for determining the solubility parameters and predicting miscibility of pharmaceutical compounds. © 2011 American Chemical Society

Improved Density Functional Tight Binding Potentials for Metalloid Aluminum Clusters

DTIC Science & Technology

2016-06-01

simulations of the oxidation of Al4Cp * 4 show reasonable comparison with a DFT-based Car -Parrinello method, including correct prediction of hydride transfers...comparison with a DFT-based Car -Parrinello method, including correct prediction of hydride transfers from Cp* to the metal centers during the...initio molecular dynamics of the oxidation of Al4Cp * 4 using a DFT-based Car -Parrinello method. This simulation, which 43 several months on the

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

de Hatten, Xavier; Cournia, Zoe; Huc, Ivan

The increasing importance of hydrogenase enzymes in the new energy research field has led us to examine the structure and dynamics of potential hydrogenase mimics, based on a ferrocene-peptide scaffold, using molecular dynamics (MD) simulations. To enable this MD study, a molecular mechanics force field for ferrocene-bearing peptides was developed and implemented in the CHARMM simulation package, thus extending the usefulness of the package into peptide-bioorganometallic chemistry. Using the automated frequency-matching method (AFMM), optimized intramolecular force-field parameters were generated through quantum chemical reference normal modes. The partial charges for ferrocene were derived by fitting point charges to quantum-chemically computed electrostaticmore » potentials. The force field was tested against experimental X-ray crystal structures of dipeptide derivatives of ferrocene-1,1'-dicarboxylic acid. The calculations reproduce accurately the molecular geometries, including the characteristic C{sub 2}-symmetrical intramolecular hydrogen-bonding pattern, that were stable over 0.1 {micro}s MD simulations. The crystal packing properties of ferrocene-1-(D)alanine-(D)proline-1'-(D)alanine-(D)proline were also accurately reproduced. The lattice parameters of this crystal were conserved during a 0.1 {micro}s MD simulation and match the experimental values almost exactly. Simulations of the peptides in dichloromethane are also in good agreement with experimental NMR and circular dichroism (CD) data in solution. The developed force field was used to perform MD simulations on novel, as yet unsynthesized peptide fragments that surround the active site of [Ni-Fe] hydrogenase. The results of this simulation lead us to propose an improved design for synthetic peptide-based hydrogenase models. The presented MD simulation results of metallocenes thereby provide a convincing validation of our proposal to use ferrocene-peptides as minimal enzyme mimics.« less

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

De Hatten, Xavier; Cournia, Zoe; Smith, Jeremy C

The increasing importance of hydrogenase enzymes in the new energy research field has led us to examine the structure and dynamics of potential hydrogenase mimics, based on a ferrocene-peptide scaffold, using molecular dynamics (MD) simulations. To enable this MD study, a molecular mechanics force field for ferrocene-bearing peptides was developed and implemented in the CHARMM simulation package, thus extending the usefulness of the package into peptide-bioorganometallic chemistry. Using the automated frequency-matching method (AFMM), optimized intramolecular force-field parameters were generated through quantum chemical reference normal modes. The partial charges for ferrocene were derived by fitting point charges to quantum-chemically computed electrostaticmore » potentials. The force field was tested against experimental X-ray crystal structures of dipeptide derivatives of ferrocene-1,1{prime}-dicarboxylic acid. The calculations reproduce accurately the molecular geometries, including the characteristic C2-symmetrical intramolecular hydrogen-bonding pattern, that were stable over 0.1{micro}s MD simulations. The crystal packing properties of ferrocene-1-(D)alanine-(D)proline{prime}-1-(D)alanine-(D)proline were also accurately reproduced. The lattice parameters of this crystal were conserved during a 0.1 s MD simulation and match the experimental values almost exactly. Simulations of the peptides in dichloromethane are also in good agreement with experimental NMR and circular dichroism (CD) data in solution. The developed force field was used to perform MD simulations on novel, as yet unsynthesized peptide fragments that surround the active site of [Ni-Fe] hydrogenase. The results of this simulation lead us to propose an improved design for synthetic peptide-based hydrogenase models. The presented MD simulation results of metallocenes thereby provide a convincing validation of our proposal to use ferrocene-peptides as minimal enzyme mimics.« less

Sequence-dependent DNA deformability studied using molecular dynamics simulations.

PubMed

Fujii, Satoshi; Kono, Hidetoshi; Takenaka, Shigeori; Go, Nobuhiro; Sarai, Akinori

2007-01-01

Proteins recognize specific DNA sequences not only through direct contact between amino acids and bases, but also indirectly based on the sequence-dependent conformation and deformability of the DNA (indirect readout). We used molecular dynamics simulations to analyze the sequence-dependent DNA conformations of all 136 possible tetrameric sequences sandwiched between CGCG sequences. The deformability of dimeric steps obtained by the simulations is consistent with that by the crystal structures. The simulation results further showed that the conformation and deformability of the tetramers can highly depend on the flanking base pairs. The conformations of xATx tetramers show the most rigidity and are not affected by the flanking base pairs and the xYRx show by contrast the greatest flexibility and change their conformations depending on the base pairs at both ends, suggesting tetramers with the same central dimer can show different deformabilities. These results suggest that analysis of dimeric steps alone may overlook some conformational features of DNA and provide insight into the mechanism of indirect readout during protein-DNA recognition. Moreover, the sequence dependence of DNA conformation and deformability may be used to estimate the contribution of indirect readout to the specificity of protein-DNA recognition as well as nucleosome positioning and large-scale behavior of nucleic acids.

Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase.

PubMed

Iman, Maryam; Khansefid, Zeynab; Davood, Asghar

2016-01-01

Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of hydroxyurea in RNR inhibition as anticancer agent. The binding affinity of hydroxyurea and compound III to RNR was studied by docking method. The docking study was performed for the crystal structure of human RNR with the radical scavenger Hydroxyurea and its oxidized form to inhibit the human RNR. hydroxyurea and compound III bind at the active site with Tyr-176, which are essential for free radical formation. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2. To confirm the binding mode of inhibitors, the molecular dynamics (MD) simulations were performed using GROMACS 4.5.5, based upon the docked conformation of inhibitors. Both of the studied compounds stayed in the active site. The results of MD simulations confirmed the binding mode of ligands, accuracy of docking and the reliability of active conformations which were obtained by AutoDock. MD studies confirm our proposed mechanism in which compound III reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme.

Molecular Dynamics based on a Generalized Born solvation model: application to protein folding

NASA Astrophysics Data System (ADS)

Onufriev, Alexey

2004-03-01

An accurate description of the aqueous environment is essential for realistic biomolecular simulations, but may become very expensive computationally. We have developed a version of the Generalized Born model suitable for describing large conformational changes in macromolecules. The model represents the solvent implicitly as continuum with the dielectric properties of water, and include charge screening effects of salt. The computational cost associated with the use of this model in Molecular Dynamics simulations is generally considerably smaller than the cost of representing water explicitly. Also, compared to traditional Molecular Dynamics simulations based on explicit water representation, conformational changes occur much faster in implicit solvation environment due to the absence of viscosity. The combined speed-up allow one to probe conformational changes that occur on much longer effective time-scales. We apply the model to folding of a 46-residue three helix bundle protein (residues 10-55 of protein A, PDB ID 1BDD). Starting from an unfolded structure at 450 K, the protein folds to the lowest energy state in 6 ns of simulation time, which takes about a day on a 16 processor SGI machine. The predicted structure differs from the native one by 2.4 A (backbone RMSD). Analysis of the structures seen on the folding pathway reveals details of the folding process unavailable form experiment.

Computational Nanotechnology at NASA Ames Research Center, 1996

NASA Technical Reports Server (NTRS)

Globus, Al; Bailey, David; Langhoff, Steve; Pohorille, Andrew; Levit, Creon; Chancellor, Marisa K. (Technical Monitor)

1996-01-01

Some forms of nanotechnology appear to have enormous potential to improve aerospace and computer systems; computational nanotechnology, the design and simulation of programmable molecular machines, is crucial to progress. NASA Ames Research Center has begun a computational nanotechnology program including in-house work, external research grants, and grants of supercomputer time. Four goals have been established: (1) Simulate a hypothetical programmable molecular machine replicating itself and building other products. (2) Develop molecular manufacturing CAD (computer aided design) software and use it to design molecular manufacturing systems and products of aerospace interest, including computer components. (3) Characterize nanotechnologically accessible materials of aerospace interest. Such materials may have excellent strength and thermal properties. (4) Collaborate with experimentalists. Current in-house activities include: (1) Development of NanoDesign, software to design and simulate a nanotechnology based on functionalized fullerenes. Early work focuses on gears. (2) A design for high density atomically precise memory. (3) Design of nanotechnology systems based on biology. (4) Characterization of diamonoid mechanosynthetic pathways. (5) Studies of the laplacian of the electronic charge density to understand molecular structure and reactivity. (6) Studies of entropic effects during self-assembly. Characterization of properties of matter for clusters up to sizes exhibiting bulk properties. In addition, the NAS (NASA Advanced Supercomputing) supercomputer division sponsored a workshop on computational molecular nanotechnology on March 4-5, 1996 held at NASA Ames Research Center. Finally, collaborations with Bill Goddard at CalTech, Ralph Merkle at Xerox Parc, Don Brenner at NCSU (North Carolina State University), Tom McKendree at Hughes, and Todd Wipke at UCSC are underway.

Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.

PubMed

Chen, Kai; Duan, Wenxiu; Han, Qianqian; Sun, Xuan; Li, Wenqian; Hu, Shuangyun; Wan, Jiajia; Wu, Jiang; Ge, Yushu; Liu, Dan

2018-03-08

Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures. The reported orally bioavailable 1 h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the catalytic site, while natural substrate ATP could not stay. Comparative study of stability and flexibility of three systems reveals position shifting of β-sheet region within the catalytic site, which indicates inhibition mechanism was through stabilizing the β-sheet region. Binding free energies calculated with MM-GB/PBSA method shows different binding affinity for inhibitor and ATP. Finally, interactions between protein and inhibitor during molecular dynamic simulations were measured and counted. Residue Gly605 and Leu654 were suggested as important hot spots for stable binding of inhibitor by molecular dynamic simulation. Our results reveal an important position shifting within catalytic site for non-inhibited proteins. Together with hot spots found by molecular dynamic simulation, the results provide important information of inhibition mechanism and will be referenced for designing novel inhibitors.

Structured water in polyelectrolyte dendrimers: Understanding small angle neutron scattering results through atomistic simulation

NASA Astrophysics Data System (ADS)

Wu, Bin; Kerkeni, Boutheïna; Egami, Takeshi; Do, Changwoo; Liu, Yun; Wang, Yongmei; Porcar, Lionel; Hong, Kunlun; Smith, Sean C.; Liu, Emily L.; Smith, Gregory S.; Chen, Wei-Ren

2012-04-01

Based on atomistic molecular dynamics (MD) simulations, the small angle neutron scattering (SANS) intensity behavior of a single generation-4 polyelectrolyte polyamidoamine starburst dendrimer is investigated at different levels of molecular protonation. The SANS form factor, P(Q), and Debye autocorrelation function, γ(r), are calculated from the equilibrium MD trajectory based on a mathematical approach proposed in this work. The consistency found in comparison against previously published experimental findings (W.-R. Chen, L. Porcar, Y. Liu, P. D. Butler, and L. J. Magid, Macromolecules 40, 5887 (2007)) leads to a link between the neutron scattering experiment and MD computation, and fresh perspectives. The simulations enable scattering calculations of not only the hydrocarbons but also the contribution from the scattering length density fluctuations caused by structured, confined water within the dendrimer. Based on our computational results, we explore the validity of using radius of gyration RG for microstructure characterization of a polyelectrolyte dendrimer from the scattering perspective.

Active food packaging based on molecularly imprinted polymers: study of the release kinetics of ferulic acid.

PubMed

Otero-Pazos, Pablo; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Benito-Peña, Elena; González-Vallejo, Victoria; Moreno-Bondi, M Cruz; Angulo, Immaculada; Paseiro-Losada, Perfecto

2014-11-19

A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples.

Cation solvation with quantum chemical effects modeled by a size-consistent multi-partitioning quantum mechanics/molecular mechanics method.

PubMed

Watanabe, Hiroshi C; Kubillus, Maximilian; Kubař, Tomáš; Stach, Robert; Mizaikoff, Boris; Ishikita, Hiroshi

2017-07-21

In the condensed phase, quantum chemical properties such as many-body effects and intermolecular charge fluctuations are critical determinants of the solvation structure and dynamics. Thus, a quantum mechanical (QM) molecular description is required for both solute and solvent to incorporate these properties. However, it is challenging to conduct molecular dynamics (MD) simulations for condensed systems of sufficient scale when adapting QM potentials. To overcome this problem, we recently developed the size-consistent multi-partitioning (SCMP) quantum mechanics/molecular mechanics (QM/MM) method and realized stable and accurate MD simulations, using the QM potential to a benchmark system. In the present study, as the first application of the SCMP method, we have investigated the structures and dynamics of Na + , K + , and Ca 2+ solutions based on nanosecond-scale sampling, a sampling 100-times longer than that of conventional QM-based samplings. Furthermore, we have evaluated two dynamic properties, the diffusion coefficient and difference spectra, with high statistical certainty. Furthermore the calculation of these properties has not previously been possible within the conventional QM/MM framework. Based on our analysis, we have quantitatively evaluated the quantum chemical solvation effects, which show distinct differences between the cations.

Molecular dynamic simulations on TKX-50/RDX cocrystal.

PubMed

Xiong, Shuling; Chen, Shusen; Jin, Shaohua

2017-06-01

Dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) is a newly synthesized energetic material with excellent comprehensive properties. Cyclotrimethylenetrinitramine (RDX) is currently one of the most widely used energetic materials in the world. TKX-50 and RDX supercell models and TKX-50/RDX cocrystal model were constructed based on their crystal cell parameters and the formation mechanism of cocrystal, respectively, then they were simulated by molecular dynamics (MD) simulations. The maximum trigger bond (NNO 2 ) length(L max ), binding energy (E bind ), radial distribution function (RDF), cohesive energy density(CED) and mechanical properties were simulated at different temperatures based on the simulated equilibrium structures of the models. The simulated results indicate that hydrogen bond and van der Waals force interactions exist in the cocrystal system and the hydrogen bonds are mainly derived from the hydrogen atom of TKX-50 with the oxygen or nitrogen atom of RDX. Moreover, TKX-50/RDX cocrystal structure significantly reduces the sensitivity and improves the thermodynamic stability of RDX, and it also shows better mechanical properties than pure TKX-50 and RDX, indicating that it will vastly expand the application scope of the single compound explosives. Copyright © 2017 Elsevier Inc. All rights reserved.

Amphiphilic interactions of ionic liquids with lipid biomembranes: a molecular simulation study.

PubMed

Yoo, Brian; Shah, Jindal K; Zhu, Yingxi; Maginn, Edward J

2014-11-21

Current bottlenecks in the large-scale commercial use of many ionic liquids (ILs) include their high costs, low biodegradability, and often unknown toxicities. As a proactive effort to better understand the molecular mechanisms of ionic liquid toxicities, the work herein presents a comprehensive molecular simulation study on the interactions of 1-n-alkyl-3-methylimidazolium-based ILs with a phosphatidylcholine (PC) lipid bilayer. We explore the effects of increasing alkyl chain length (n = 4, 8, and 12) in the cation and anion hydrophobicity on the interactions with the lipid bilayer. Bulk atomistic molecular dynamics (MD) simulations performed at millimolar (mM) IL concentrations show spontaneous insertion of cations into the lipid bilayer regardless of the alkyl chain length and a favorable orientational preference once a cation is inserted. Cations also exhibit the ability to "flip" inside the lipid bilayer (as is common for amphiphiles) if partially inserted with an unfavorable orientation. Moreover, structural analysis of the lipid bilayer show that cationic insertion induces roughening of the bilayer surface, which may be a precursor to bilayer disruption. To overcome the limitation in the timescale of our simulations, free energies for a single IL cation and anion insertion have been determined based on potential of mean force calculations. These results show a decrease in free energy in response to both short and long alkyl chain IL cation insertion, and likewise for a single hydrophobic anion insertion, but an increase in free energy for the insertion of a hydrophilic chloride anion. Both bulk MD simulations and free energy calculations suggest that toxicity mechanisms toward biological systems are likely caused by ILs behaving as ionic surfactants. [Yoo et al., Soft Matter, 2014].

Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors.

PubMed

Rastija, Vesna; Agić, Dejan; Tomiš, Sanja; Nikolič, Sonja; Hranjec, Marijana; Grace, Karminski-Zamola; Abramić, Marija

2015-01-01

A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure-Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III.

GPU-enabled molecular dynamics simulations of ankyrin kinase complex

NASA Astrophysics Data System (ADS)

Gautam, Vertika; Chong, Wei Lim; Wisitponchai, Tanchanok; Nimmanpipug, Piyarat; Zain, Sharifuddin M.; Rahman, Noorsaadah Abd.; Tayapiwatana, Chatchai; Lee, Vannajan Sanghiran

2014-10-01

The ankyrin repeat (AR) protein can be used as a versatile scaffold for protein-protein interactions. It has been found that the heterotrimeric complex between integrin-linked kinase (ILK), PINCH, and parvin is an essential signaling platform, serving as a convergence point for integrin and growth-factor signaling and regulating cell adhesion, spreading, and migration. Using ILK-AR with high affinity for the PINCH1 as our model system, we explored a structure-based computational protocol to probe and characterize binding affinity hot spots at protein-protein interfaces. In this study, the long time scale dynamics simulations with GPU accelerated molecular dynamics (MD) simulations in AMBER12 have been performed to locate the hot spots of protein-protein interaction by the analysis of the Molecular Mechanics-Poisson-Boltzmann Surface Area/Generalized Born Solvent Area (MM-PBSA/GBSA) of the MD trajectories. Our calculations suggest good binding affinity of the complex and also the residues critical in the binding.

Atomic concentration effect on thermal properties during solidification of Pt-Rh alloy: A molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Yildiz, A. K.; Celik, F. A.

2017-04-01

The solidification process of Platinum-Rhodium alloy from liquid phase to solid state is investigated at the nano-scale by using Molecular Dynamics Simulation (MDS) for different atomic concentration ratios of Pt. The critical nucleus radius, the bond order parameter, interfacial free energies and total energy based on nucleation theory of the alloy are examined with respect to the temperature changes. The heat of fusion from high temperatures to low temperatures during solidification of the alloy system is determined from molecular dynamics simulation. The structural development is determined from the radial distribution function. It is observed from the results that the melting point of the alloy system decreases with increasing concentration of Pt and that variation of Pt ratio in the alloy shows a remarkable effect on solidification to understand the cooling process of thermal effects.

A Review of Enhanced Sampling Approaches for Accelerated Molecular Dynamics

NASA Astrophysics Data System (ADS)

Tiwary, Pratyush; van de Walle, Axel

Molecular dynamics (MD) simulations have become a tool of immense use and popularity for simulating a variety of systems. With the advent of massively parallel computer resources, one now routinely sees applications of MD to systems as large as hundreds of thousands to even several million atoms, which is almost the size of most nanomaterials. However, it is not yet possible to reach laboratory timescales of milliseconds and beyond with MD simulations. Due to the essentially sequential nature of time, parallel computers have been of limited use in solving this so-called timescale problem. Instead, over the years a large range of statistical mechanics based enhanced sampling approaches have been proposed for accelerating molecular dynamics, and accessing timescales that are well beyond the reach of the fastest computers. In this review we provide an overview of these approaches, including the underlying theory, typical applications, and publicly available software resources to implement them.

Self-Assembly of Molecular Threads into Reversible Gels

NASA Astrophysics Data System (ADS)

Sayar, Mehmet; Stupp, Samuel I.

2001-03-01

Reversible gels formed by low concentrations of molecular gelators that self-assemble into fibers with molecular width and extremely long length have been studied via Monte Carlo simulations. The gelators of interest have two kinds of interactions, one governs self-assembly into fibers and the other provides inter-fiber connectivity to drive the formation of a network. The off-lattice Monte Carlo simulation presented here is based on a point particle representation of gelators. In this model each particle can form only two strong bonds, that enable linear fiber formation, but a variable number of weak bonds which provide inter-fiber connectivity. The gel formation has been studied as a function of concentration of monomers, the strength of interactions, number of bonding sites per particle for weak interactions, and the stiffness of the fibers. The simulation results are compared with two experimental systems synthesized in our group in order to understand gelation mechanisms.

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics

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

Martínez, Enrique; Cawkwell, Marc J.; Voter, Arthur F.

Here, Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached atmore » each time step. Lastly, the thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.« less

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics

DOE PAGES

Martínez, Enrique; Cawkwell, Marc J.; Voter, Arthur F.; ...

2015-04-21

Here, Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached atmore » each time step. Lastly, the thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.« less

MM/PBSA analysis of molecular dynamics simulations of bovine beta-lactoglobulin: free energy gradients in conformational transitions?

PubMed

Fogolari, Federico; Moroni, Elisabetta; Wojciechowski, Marcin; Baginski, Maciej; Ragona, Laura; Molinari, Henriette

2005-04-01

The pH-driven opening and closure of beta-lactoglobulin EF loop, acting as a lid and closing the internal cavity of the protein, has been studied by molecular dynamics (MD) simulations and free energy calculations based on molecular mechanics/Poisson-Boltzmann (PB) solvent-accessible surface area (MM/PBSA) methodology. The forms above and below the transition pH differ presumably only in the protonation state of residue Glu89. MM/PBSA calculations are able to reproduce qualitatively the thermodynamics of the transition. The analysis of MD simulations using a combination of MM/PBSA methodology and the colony energy approach is able to highlight the driving forces implied in the transition. The analysis suggests that global rearrangements take place before the equilibrium local conformation is reached. This conclusion may bear general relevance to conformational transitions in all lipocalins and proteins in general. (c) 2005 Wiley-Liss, Inc.

Mixed quantum-classical simulations of the vibrational relaxation of photolyzed carbon monoxide in a hemoprotein

NASA Astrophysics Data System (ADS)

Schubert, Alexander; Falvo, Cyril; Meier, Christoph

2016-08-01

We present mixed quantum-classical simulations on relaxation and dephasing of vibrationally excited carbon monoxide within a protein environment. The methodology is based on a vibrational surface hopping approach treating the vibrational states of CO quantum mechanically, while all remaining degrees of freedom are described by means of classical molecular dynamics. The CO vibrational states form the "surfaces" for the classical trajectories of protein and solvent atoms. In return, environmentally induced non-adiabatic couplings between these states cause transitions describing the vibrational relaxation from first principles. The molecular dynamics simulation yields a detailed atomistic picture of the energy relaxation pathways, taking the molecular structure and dynamics of the protein and its solvent fully into account. Using the ultrafast photolysis of CO in the hemoprotein FixL as an example, we study the relaxation of vibrationally excited CO and evaluate the role of each of the FixL residues forming the heme pocket.

Weighted Distance Functions Improve Analysis of High-Dimensional Data: Application to Molecular Dynamics Simulations.

PubMed

Blöchliger, Nicolas; Caflisch, Amedeo; Vitalis, Andreas

2015-11-10

Data mining techniques depend strongly on how the data are represented and how distance between samples is measured. High-dimensional data often contain a large number of irrelevant dimensions (features) for a given query. These features act as noise and obfuscate relevant information. Unsupervised approaches to mine such data require distance measures that can account for feature relevance. Molecular dynamics simulations produce high-dimensional data sets describing molecules observed in time. Here, we propose to globally or locally weight simulation features based on effective rates. This emphasizes, in a data-driven manner, slow degrees of freedom that often report on the metastable states sampled by the molecular system. We couple this idea to several unsupervised learning protocols. Our approach unmasks slow side chain dynamics within the native state of a miniprotein and reveals additional metastable conformations of a protein. The approach can be combined with most algorithms for clustering or dimensionality reduction.

Communication: Quantum molecular dynamics simulation of liquid para-hydrogen by nuclear and electron wave packet approach

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

Hyeon-Deuk, Kim, E-mail: kim@kuchem.kyoto-u.ac.jp; Japan Science and Technology Agency, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012; Ando, Koji

2014-05-07

Liquid para-hydrogen (p-H{sub 2}) is a typical quantum liquid which exhibits strong nuclear quantum effects (NQEs) and thus anomalous static and dynamic properties. We propose a real-time simulation method of wave packet (WP) molecular dynamics (MD) based on non-empirical intra- and inter-molecular interactions of non-spherical hydrogen molecules, and apply it to condensed-phase p-H{sub 2}. The NQEs, such as WP delocalization and zero-point energy, are taken into account without perturbative expansion of prepared model potential functions but with explicit interactions between nuclear and electron WPs. The developed MD simulation for 100 ps with 1200 hydrogen molecules is realized at feasible computationalmore » cost, by which basic experimental properties of p-H{sub 2} liquid such as radial distribution functions, self-diffusion coefficients, and shear viscosities are all well reproduced.« less

A parallel algorithm for step- and chain-growth polymerization in molecular dynamics.

PubMed

de Buyl, Pierre; Nies, Erik

2015-04-07

Classical Molecular Dynamics (MD) simulations provide insight into the properties of many soft-matter systems. In some situations, it is interesting to model the creation of chemical bonds, a process that is not part of the MD framework. In this context, we propose a parallel algorithm for step- and chain-growth polymerization that is based on a generic reaction scheme, works at a given intrinsic rate and produces continuous trajectories. We present an implementation in the ESPResSo++ simulation software and compare it with the corresponding feature in LAMMPS. For chain growth, our results are compared to the existing simulation literature. For step growth, a rate equation is proposed for the evolution of the crosslinker population that compares well to the simulations for low crosslinker functionality or for short times.

A parallel algorithm for step- and chain-growth polymerization in molecular dynamics

NASA Astrophysics Data System (ADS)

de Buyl, Pierre; Nies, Erik

2015-04-01

Classical Molecular Dynamics (MD) simulations provide insight into the properties of many soft-matter systems. In some situations, it is interesting to model the creation of chemical bonds, a process that is not part of the MD framework. In this context, we propose a parallel algorithm for step- and chain-growth polymerization that is based on a generic reaction scheme, works at a given intrinsic rate and produces continuous trajectories. We present an implementation in the ESPResSo++ simulation software and compare it with the corresponding feature in LAMMPS. For chain growth, our results are compared to the existing simulation literature. For step growth, a rate equation is proposed for the evolution of the crosslinker population that compares well to the simulations for low crosslinker functionality or for short times.

Mesoscale energy deposition footprint model for kiloelectronvolt cluster bombardment of solids.

PubMed

Russo, Michael F; Garrison, Barbara J

2006-10-15

Molecular dynamics simulations have been performed to model 5-keV C60 and Au3 projectile bombardment of an amorphous water substrate. The goal is to obtain detailed insights into the dynamics of motion in order to develop a straightforward and less computationally demanding model of the process of ejection. The molecular dynamics results provide the basis for the mesoscale energy deposition footprint model. This model provides a method for predicting relative yields based on information from less than 1 ps of simulation time.

Reactive molecular simulation on the calcium silicate hydrates/polyethylene glycol composites

NASA Astrophysics Data System (ADS)

Zhou, Yang; Hou, Dongshuai; Jiang, Jinyang; She, Wei; Yu, Jiao

2017-11-01

Calcium silicate hydrates (C-S-H) may potentially exhibit extraordinary performance when modified by polymers, in which way the properties of cement-based materials can be improved from the genetic level. In this molecular dynamics simulation of the interaction between C-S-H and polyethylene glycol, apart from the H bond network connection in the interface, another chemical adsorption was observed. Calcium of C-S-H broke the Csbnd O bond of PEG and formed a new Casbnd C connection, which created a stronger link between the organic and inorganic phases.

Comment on "Comment on 'Constant temperature molecular dynamics simulations by means of a stochastic collision model. II. The harmonic oscillator' [J. Chem. Phys. 104, 3732 (1996)]" [J. Chem. Phys. 106, 1646 (1997)].

PubMed

Kast, Stefan M

2004-03-08

An argument brought forward by Sholl and Fichthorn against the stochastic collision-based constant temperature algorithm for molecular dynamics simulations developed by Kast et al. is refuted. It is demonstrated that the large temperature fluctuations noted by Sholl and Fichthorn are due to improperly chosen initial conditions within their formulation of the algorithm. With the original form or by suitable initialization of their variant no deficient behavior is observed.

Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations

PubMed Central

Okazaki, Kei-ichi; Koga, Nobuyasu; Takada, Shoji; Onuchic, Jose N.; Wolynes, Peter G.

2006-01-01

Biomolecules often undergo large-amplitude motions when they bind or release other molecules. Unlike macroscopic machines, these biomolecular machines can partially disassemble (unfold) and then reassemble (fold) during such transitions. Here we put forward a minimal structure-based model, the “multiple-basin model,” that can directly be used for molecular dynamics simulation of even very large biomolecular systems so long as the endpoints of the conformational change are known. We investigate the model by simulating large-scale motions of four proteins: glutamine-binding protein, S100A6, dihydrofolate reductase, and HIV-1 protease. The mechanisms of conformational transition depend on the protein basin topologies and change with temperature near the folding transition. The conformational transition rate varies linearly with driving force over a fairly large range. This linearity appears to be a consequence of partial unfolding during the conformational transition. PMID:16877541

Optimization and performance evaluation of a conical mirror based fluorescence molecular tomography imaging system

NASA Astrophysics Data System (ADS)

Zhao, Yue; Zhang, Wei; Zhu, Dianwen; Li, Changqing

2016-03-01

We performed numerical simulations and phantom experiments with a conical mirror based fluorescence molecular tomography (FMT) imaging system to optimize its performance. With phantom experiments, we have compared three measurement modes in FMT: the whole surface measurement mode, the transmission mode, and the reflection mode. Our results indicated that the whole surface measurement mode performed the best. Then, we applied two different neutral density (ND) filters to improve the measurement's dynamic range. The benefits from ND filters are not as much as predicted. Finally, with numerical simulations, we have compared two laser excitation patterns: line and point. With the same excitation position number, we found that the line laser excitation had slightly better FMT reconstruction results than the point laser excitation. In the future, we will implement Monte Carlo ray tracing simulations to calculate multiple reflection photons, and create a look-up table accordingly for calibration.

Computing the Absorption and Emission Spectra of 5-Methylcytidine in Different Solvents: A Test-Case for Different Solvation Models.

PubMed

Martínez-Fernández, L; Pepino, A J; Segarra-Martí, J; Banyasz, A; Garavelli, M; Improta, R

2016-09-13

The optical spectra of 5-methylcytidine in three different solvents (tetrahydrofuran, acetonitrile, and water) is measured, showing that both the absorption and the emission maximum in water are significantly blue-shifted (0.08 eV). The absorption spectra are simulated based on CAM-B3LYP/TD-DFT calculations but including solvent effects with three different approaches: (i) a hybrid implicit/explicit full quantum mechanical approach, (ii) a mixed QM/MM static approach, and (iii) a QM/MM method exploiting the structures issuing from molecular dynamics classical simulations. Ab-initio Molecular dynamics simulations based on CAM-B3LYP functionals have also been performed. The adopted approaches all reproduce the main features of the experimental spectra, giving insights on the chemical-physical effects responsible for the solvent shifts in the spectra of 5-methylcytidine and providing the basis for discussing advantages and limitations of the adopted solvation models.

Molecular dynamics simulation of premelting and melting phase transitions in stoichiometric uranium dioxide

NASA Astrophysics Data System (ADS)

Yakub, Eugene; Ronchi, Claudio; Staicu, Dragos

2007-09-01

Results of molecular dynamics (MD) simulation of UO2 in a wide temperature range are presented and discussed. A new approach to the calibration of a partly ionic Busing-Ida-type model is proposed. A potential parameter set is obtained reproducing the experimental density of solid UO2 in a wide range of temperatures. A conventional simulation of the high-temperature stoichiometric UO2 on large MD cells, based on a novel fast method of computation of Coulomb forces, reveals characteristic features of a premelting λ transition at a temperature near to that experimentally observed (Tλ=2670K ). A strong deviation from the Arrhenius behavior of the oxygen self-diffusion coefficient was found in the vicinity of the transition point. Predictions for liquid UO2, based on the same potential parameter set, are in good agreement with existing experimental data and theoretical calculations.

Dissipative particle dynamics simulations of polymersomes.

PubMed

Ortiz, Vanessa; Nielsen, Steven O; Discher, Dennis E; Klein, Michael L; Lipowsky, Reinhard; Shillcock, Julian

2005-09-22

A DPD model of PEO-based block copolymer vesicles in water is developed by introducing a new density based coarse graining and by using experimental data for interfacial tension. Simulated as a membrane patch, the DPD model is in excellent agreement with experimental data for both the area expansion modulus and the scaling of hydrophobic core thickness with molecular weight. Rupture simulations of polymer vesicles, or "polymersomes", are presented to illustrate the system sizes feasible with DPD. The results should provide guidance for theoretical derivations of scaling laws and also illustrate how spherical polymer vesicles might be studied in simulation.

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

Molecular dynamics study on the evolution of interfacial dislocation network and mechanical properties of Ni-based single crystal superalloys

NASA Astrophysics Data System (ADS)

Li, Nan-Lin; Wu, Wen-Ping; Nie, Kai

2018-05-01

The evolution of misfit dislocation network at γ /γ‧ phase interface and tensile mechanical properties of Ni-based single crystal superalloys at various temperatures and strain rates are studied by using molecular dynamics (MD) simulations. From the simulations, it is found that with the increase of loading, the dislocation network effectively inhibits dislocations emitted in the γ matrix cutting into the γ‧ phase and absorbs the matrix dislocations to strengthen itself which increases the stability of structure. Under the influence of the temperature, the initial mosaic structure of dislocation network gradually becomes irregular, and the initial misfit stress and the elastic modulus slowly decline as temperature increasing. On the other hand, with the increase of the strain rate, it almost has no effect on the elastic modulus and the way of evolution of dislocation network, but contributes to the increases of the yield stress and tensile strength. Moreover, tension-compression asymmetry of Ni-based single crystal superalloys is also presented based on MD simulations.

Scaling Atomic Partial Charges of Carbonate Solvents for Lithium Ion Solvation and Diffusion

DOE PAGES

Chaudhari, Mangesh I.; Nair, Jijeesh R.; Pratt, Lawrence R.; ...

2016-10-21

Lithium-ion solvation and diffusion properties in ethylene carbonate (EC) and propylene carbonate (PC) were studied by molecular simulation, experiments, and electronic structure calculations. Studies carried out in water provide a reference for interpretation. Classical molecular dynamics simulation results are compared to ab initio molecular dynamics to assess nonpolarizable force field parameters for solvation structure of the carbonate solvents. Quasi-chemical theory (QCT) was adapted to take advantage of fourfold occupancy of the near-neighbor solvation structure observed in simulations and used to calculate solvation free energies. The computed free energy for transfer of Li + to PC from water, based on electronicmore » structure calculations with cluster-QCT, agrees with the experimental value. The simulation-based direct-QCT results with scaled partial charges agree with the electronic structure-based QCT values. The computed Li +/PF 6 - transference numbers of 0.35/0.65 (EC) and 0.31/0.69 (PC) agree well with NMR experimental values of 0.31/0.69 (EC) and 0.34/0.66 (PC) and similar values obtained here with impedance spectroscopy. These combined results demonstrate that solvent partial charges can be scaled in systems dominated by strong electrostatic interactions to achieve trends in ion solvation and transport properties that are comparable to ab initio and experimental results. Thus, the results support the use of scaled partial charges in simple, nonpolarizable force fields in future studies of these electrolyte solutions.« less

Selectivity trend of gas separation through nanoporous graphene

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

Liu, Hongjun; Chen, Zhongfang; Dai, Sheng

2014-01-29

We demonstrate that porous graphene can efficiently separate gases according to their molecular sizes using molecular dynamic (MD) simulations,. The flux sequence from the classical MD simulation is H 2>CO 2>>N 2>Ar>CH 4, which generally follows the trend in the kinetic diameters. Moreover, this trend is also confirmed from the fluxes based on the computed free energy barriers for gas permeation using the umbrella sampling method and kinetic theory of gases. Both brute-force MD simulations and free-energy calcualtions lead to the flux trend consistent with experiments. Case studies of two compositions of CO 2/N 2 mixtures further demonstrate the separationmore » capability of nanoporous graphene.« less

Investigating Small-Molecule Ligand Binding to G Protein-Coupled Receptors with Biased or Unbiased Molecular Dynamics Simulations

PubMed Central

Marino, Kristen A.; Filizola, Marta

2017-01-01

An increasing number of G protein-coupled receptor (GPCR) crystal structures provide important—albeit static—pictures of how small molecules or peptides interact with their receptors. These high-resolution structures represent a tremendous opportunity to apply molecular dynamics (MD) simulations to capture atomic-level dynamical information that is not easy to obtain experimentally. Understanding ligand binding and unbinding processes, as well as the related responses of the receptor, is crucial to the design of better drugs targeting GPCRs. Here, we discuss possible ways to study the dynamics involved in the binding of small molecules to GPCRs, using long timescale MD simulations or metadynamics-based approaches. PMID:29188572

Investigating Small-Molecule Ligand Binding to G Protein-Coupled Receptors with Biased or Unbiased Molecular Dynamics Simulations.

PubMed

Marino, Kristen A; Filizola, Marta

2018-01-01

An increasing number of G protein-coupled receptor (GPCR) crystal structures provide important-albeit static-pictures of how small molecules or peptides interact with their receptors. These high-resolution structures represent a tremendous opportunity to apply molecular dynamics (MD) simulations to capture atomic-level dynamical information that is not easy to obtain experimentally. Understanding ligand binding and unbinding processes, as well as the related responses of the receptor, is crucial to the design of better drugs targeting GPCRs. Here, we discuss possible ways to study the dynamics involved in the binding of small molecules to GPCRs, using long timescale MD simulations or metadynamics-based approaches.

Isosteric And Non-Isosteric Base Pairs In RNA Motifs: Molecular Dynamics And Bioinformatics Study Of The Sarcin-Ricin Internal Loop

PubMed Central

Havrila, Marek; Réblová, Kamila; Zirbel, Craig L.; Leontis, Neocles B.; Šponer, Jiří

2013-01-01

The Sarcin-Ricin RNA motif (SR motif) is one of the most prominent recurrent RNA building blocks that occurs in many different RNA contexts and folds autonomously, i.e., in a context-independent manner. In this study, we combined bioinformatics analysis with explicit-solvent molecular dynamics (MD) simulations to better understand the relation between the RNA sequence and the evolutionary patterns of SR motif. SHAPE probing experiment was also performed to confirm fidelity of MD simulations. We identified 57 instances of the SR motif in a non-redundant subset of the RNA X-ray structure database and analyzed their basepairing, base-phosphate, and backbone-backbone interactions. We extracted sequences aligned to these instances from large ribosomal RNA alignments to determine frequency of occurrence for different sequence variants. We then used a simple scoring scheme based on isostericity to suggest 10 sequence variants with highly variable expected degree of compatibility with the SR motif 3D structure. We carried out MD simulations of SR motifs with these base substitutions. Non isosteric base substitutions led to unstable structures, but so did isosteric substitutions which were unable to make key base-phosphate interactions. MD technique explains why some potentially isosteric SR motifs are not realized during evolution. We also found that inability to form stable cWW geometry is an important factor in case of the first base pair of the flexible region of the SR motif. Comparison of structural, bioinformatics, SHAPE probing and MD simulation data reveals that explicit solvent MD simulations neatly reflect viability of different sequence variants of the SR motif. Thus, MD simulations can efficiently complement bioinformatics tools in studies of conservation patterns of RNA motifs and provide atomistic insight into the role of their different signature interactions. PMID:24144333

Modeling charge transport in organic photovoltaic materials.

PubMed

Nelson, Jenny; Kwiatkowski, Joe J; Kirkpatrick, James; Frost, Jarvist M

2009-11-17

The performance of an organic photovoltaic cell depends critically on the mobility of charge carriers within the constituent molecular semiconductor materials. However, a complex combination of phenomena that span a range of length and time scales control charge transport in disordered organic semiconductors. As a result, it is difficult to rationalize charge transport properties in terms of material parameters. Until now, efforts to improve charge mobilities in molecular semiconductors have proceeded largely by trial and error rather than through systematic design. However, recent developments have enabled the first predictive simulation studies of charge transport in disordered organic semiconductors. This Account describes a set of computational methods, specifically molecular modeling methods, to simulate molecular packing, quantum chemical calculations of charge transfer rates, and Monte Carlo simulations of charge transport. Using case studies, we show how this combination of methods can reproduce experimental mobilities with few or no fitting parameters. Although currently applied to material systems of high symmetry or well-defined structure, further developments of this approach could address more complex systems such anisotropic or multicomponent solids and conjugated polymers. Even with an approximate treatment of packing disorder, these computational methods simulate experimental mobilities within an order of magnitude at high electric fields. We can both reproduce the relative values of electron and hole mobility in a conjugated small molecule and rationalize those values based on the symmetry of frontier orbitals. Using fully atomistic molecular dynamics simulations of molecular packing, we can quantitatively replicate vertical charge transport along stacks of discotic liquid crystals which vary only in the structure of their side chains. We can reproduce the trends in mobility with molecular weight for self-organizing polymers using a cheap, coarse-grained structural simulation method. Finally, we quantitatively reproduce the field-effect mobility in disordered C60 films. On the basis of these results, we conclude that all of the necessary building blocks are in place for the predictive simulation of charge transport in macromolecular electronic materials and that such methods can be used as a tool toward the future rational design of functional organic electronic materials.

A software platform for continuum modeling of ion channels based on unstructured mesh

NASA Astrophysics Data System (ADS)

Tu, B.; Bai, S. Y.; Chen, M. X.; Xie, Y.; Zhang, L. B.; Lu, B. Z.

2014-01-01

Most traditional continuum molecular modeling adopted finite difference or finite volume methods which were based on a structured mesh (grid). Unstructured meshes were only occasionally used, but an increased number of applications emerge in molecular simulations. To facilitate the continuum modeling of biomolecular systems based on unstructured meshes, we are developing a software platform with tools which are particularly beneficial to those approaches. This work describes the software system specifically for the simulation of a typical, complex molecular procedure: ion transport through a three-dimensional channel system that consists of a protein and a membrane. The platform contains three parts: a meshing tool chain for ion channel systems, a parallel finite element solver for the Poisson-Nernst-Planck equations describing the electrodiffusion process of ion transport, and a visualization program for continuum molecular modeling. The meshing tool chain in the platform, which consists of a set of mesh generation tools, is able to generate high-quality surface and volume meshes for ion channel systems. The parallel finite element solver in our platform is based on the parallel adaptive finite element package PHG which wass developed by one of the authors [1]. As a featured component of the platform, a new visualization program, VCMM, has specifically been developed for continuum molecular modeling with an emphasis on providing useful facilities for unstructured mesh-based methods and for their output analysis and visualization. VCMM provides a graphic user interface and consists of three modules: a molecular module, a meshing module and a numerical module. A demonstration of the platform is provided with a study of two real proteins, the connexin 26 and hemolysin ion channels.

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

Development of a potent 2-oxoamide inhibitor of secreted phospholipase A2 guided by molecular docking calculations and molecular dynamics simulations

PubMed Central

Vasilakaki, Sofia; Barbayianni, Efrosini; Leonis, Georgios; Papadopoulos, Manthos G.; Mavromoustakos, Thomas; Gelb, Michael H.; Kokotos, George

2016-01-01

Inhibition of group IIA secreted phospholipase A2 (GIIA sPLA2) has been an important objective for medicinal chemists. We have previously shown that inhibitors incorporating the 2-oxoamide functionality may inhibit human and mouse GIIA sPLA2s. Herein, the development of new potent inhibitors by molecular docking calculations using the structure of the known inhibitor 7 as scaffold, are described. Synthesis and biological evaluation of the new compounds revealed that the long chain 2-oxoamide based on (S)-valine GK241 led to improved activity (IC50 = 143 nM and 68 nM against human and mouse GIIA sPLA2, respectively). In addition, molecular dynamics simulations were employed to shed light on GK241 potent and selective inhibitory activity. PMID:26970660

How effective are simulated molecular-level experiments for teaching diffusion and osmosis?

PubMed

Meir, Eli; Perry, Judith; Stal, Derek; Maruca, Susan; Klopfer, Eric

2005-01-01

Diffusion and osmosis are central concepts in biology, both at the cellular and organ levels. They are presented several times throughout most introductory biology textbooks (e.g., Freeman, 2002), yet both processes are often difficult for students to understand (Odom, 1995; Zuckerman, 1994; Sanger et al., 2001; and results herein). Students have deep-rooted misconceptions about how diffusion and osmosis work, especially at the molecular level. We hypothesized that this might be in part due to the inability to see and explore these processes at the molecular level. In order to investigate this, we developed new software, OsmoBeaker, which allows students to perform inquiry-based experiments at the molecular level. Here we show that these simulated laboratories do indeed teach diffusion and osmosis and help overcome some, but not all, student misconceptions.

How Effective Are Simulated Molecular-level Experiments for Teaching Diffusion and Osmosis?

PubMed Central

2005-01-01

Diffusion and osmosis are central concepts in biology, both at the cellular and organ levels. They are presented several times throughout most introductory biology textbooks (e.g., Freeman, 2002), yet both processes are often difficult for students to understand (Odom, 1995; Zuckerman, 1994; Sanger et al., 2001; and results herein). Students have deep-rooted misconceptions about how diffusion and osmosis work, especially at the molecular level. We hypothesized that this might be in part due to the inability to see and explore these processes at the molecular level. In order to investigate this, we developed new software, OsmoBeaker, which allows students to perform inquiry-based experiments at the molecular level. Here we show that these simulated laboratories do indeed teach diffusion and osmosis and help overcome some, but not all, student misconceptions. PMID:16220144

Force-field parameters from the SAFT-γ equation of state for use in coarse-grained molecular simulations.

PubMed

Müller, Erich A; Jackson, George

2014-01-01

A description of fluid systems with molecular-based algebraic equations of state (EoSs) and by direct molecular simulation is common practice in chemical engineering and the physical sciences, but the two approaches are rarely closely coupled. The key for an integrated representation is through a well-defined force field and Hamiltonian at the molecular level. In developing coarse-grained intermolecular potential functions for the fluid state, one typically starts with a detailed, bottom-up quantum-mechanical or atomic-level description and then integrates out the unwanted degrees of freedom using a variety of techniques; an iterative heuristic simulation procedure is then used to refine the parameters of the model. By contrast, with a top-down technique, one can use an accurate EoS to link the macroscopic properties of the fluid and the force-field parameters. We discuss the latest developments in a top-down representation of fluids, with a particular focus on a group-contribution formulation of the statistical associating fluid theory (SAFT-γ). The accurate SAFT-γ EoS is used to estimate the parameters of the Mie force field, which can then be used with confidence in direct molecular simulations to obtain thermodynamic, structural, interfacial, and dynamical properties that are otherwise inaccessible from the EoS. This is exemplified for several prototypical fluids and mixtures, including carbon dioxide, hydrocarbons, perfluorohydrocarbons, and aqueous surfactants.

The Virtual Liver Project: Modeling Tissue Response To Chemicals Through Multiscale Simulation

EPA Science Inventory

The US EPA Virtual Liver Project is aimed at simulating the risk of toxic effects from environmental chemicals in silico. The computational systems model of organ injury due to chronic chemical exposure is based on: (i) the dynamics of perturbed molecular pathways, (ii) their lin...

Simbios: an NIH national center for physics-based simulation of biological structures.

PubMed

Delp, Scott L; Ku, Joy P; Pande, Vijay S; Sherman, Michael A; Altman, Russ B

2012-01-01

Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations can be used by biologists to study macromolecular assemblies and by clinicians to design treatments for diseases. Simulations help biomedical researchers understand the physical constraints on biological systems as they engineer novel drugs, synthetic tissues, medical devices, and surgical interventions. Although individual biomedical investigators make outstanding contributions to physics-based simulation, the field has been fragmented. Applications are typically limited to a single physical scale, and individual investigators usually must create their own software. These conditions created a major barrier to advancing simulation capabilities. In 2004, we established a National Center for Physics-Based Simulation of Biological Structures (Simbios) to help integrate the field and accelerate biomedical research. In 6 years, Simbios has become a vibrant national center, with collaborators in 16 states and eight countries. Simbios focuses on problems at both the molecular scale and the organismal level, with a long-term goal of uniting these in accurate multiscale simulations.

Simbios: an NIH national center for physics-based simulation of biological structures

PubMed Central

Delp, Scott L; Ku, Joy P; Pande, Vijay S; Sherman, Michael A

2011-01-01

Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations can be used by biologists to study macromolecular assemblies and by clinicians to design treatments for diseases. Simulations help biomedical researchers understand the physical constraints on biological systems as they engineer novel drugs, synthetic tissues, medical devices, and surgical interventions. Although individual biomedical investigators make outstanding contributions to physics-based simulation, the field has been fragmented. Applications are typically limited to a single physical scale, and individual investigators usually must create their own software. These conditions created a major barrier to advancing simulation capabilities. In 2004, we established a National Center for Physics-Based Simulation of Biological Structures (Simbios) to help integrate the field and accelerate biomedical research. In 6 years, Simbios has become a vibrant national center, with collaborators in 16 states and eight countries. Simbios focuses on problems at both the molecular scale and the organismal level, with a long-term goal of uniting these in accurate multiscale simulations. PMID:22081222

The Development and Comparison of Molecular Dynamics Simulation and Monte Carlo Simulation

NASA Astrophysics Data System (ADS)

Chen, Jundong

2018-03-01

Molecular dynamics is an integrated technology that combines physics, mathematics and chemistry. Molecular dynamics method is a computer simulation experimental method, which is a powerful tool for studying condensed matter system. This technique not only can get the trajectory of the atom, but can also observe the microscopic details of the atomic motion. By studying the numerical integration algorithm in molecular dynamics simulation, we can not only analyze the microstructure, the motion of particles and the image of macroscopic relationship between them and the material, but can also study the relationship between the interaction and the macroscopic properties more conveniently. The Monte Carlo Simulation, similar to the molecular dynamics, is a tool for studying the micro-molecular and particle nature. In this paper, the theoretical background of computer numerical simulation is introduced, and the specific methods of numerical integration are summarized, including Verlet method, Leap-frog method and Velocity Verlet method. At the same time, the method and principle of Monte Carlo Simulation are introduced. Finally, similarities and differences of Monte Carlo Simulation and the molecular dynamics simulation are discussed.

Mixing model with multi-particle interactions for Lagrangian simulations of turbulent mixing

NASA Astrophysics Data System (ADS)

Watanabe, T.; Nagata, K.

2016-08-01

We report on the numerical study of the mixing volume model (MVM) for molecular diffusion in Lagrangian simulations of turbulent mixing problems. The MVM is based on the multi-particle interaction in a finite volume (mixing volume). A priori test of the MVM, based on the direct numerical simulations of planar jets, is conducted in the turbulent region and the interfacial layer between the turbulent and non-turbulent fluids. The results show that the MVM predicts well the mean effects of the molecular diffusion under various numerical and flow parameters. The number of the mixing particles should be large for predicting a value of the molecular diffusion term positively correlated to the exact value. The size of the mixing volume relative to the Kolmogorov scale η is important in the performance of the MVM. The scalar transfer across the turbulent/non-turbulent interface is well captured by the MVM especially with the small mixing volume. Furthermore, the MVM with multiple mixing particles is tested in the hybrid implicit large-eddy-simulation/Lagrangian-particle-simulation (LES-LPS) of the planar jet with the characteristic length of the mixing volume of O(100η). Despite the large mixing volume, the MVM works well and decays the scalar variance in a rate close to the reference LES. The statistics in the LPS are very robust to the number of the particles used in the simulations and the computational grid size of the LES. Both in the turbulent core region and the intermittent region, the LPS predicts a scalar field well correlated to the LES.

Mixing model with multi-particle interactions for Lagrangian simulations of turbulent mixing

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

Watanabe, T., E-mail: watanabe.tomoaki@c.nagoya-u.jp; Nagata, K.

We report on the numerical study of the mixing volume model (MVM) for molecular diffusion in Lagrangian simulations of turbulent mixing problems. The MVM is based on the multi-particle interaction in a finite volume (mixing volume). A priori test of the MVM, based on the direct numerical simulations of planar jets, is conducted in the turbulent region and the interfacial layer between the turbulent and non-turbulent fluids. The results show that the MVM predicts well the mean effects of the molecular diffusion under various numerical and flow parameters. The number of the mixing particles should be large for predicting amore » value of the molecular diffusion term positively correlated to the exact value. The size of the mixing volume relative to the Kolmogorov scale η is important in the performance of the MVM. The scalar transfer across the turbulent/non-turbulent interface is well captured by the MVM especially with the small mixing volume. Furthermore, the MVM with multiple mixing particles is tested in the hybrid implicit large-eddy-simulation/Lagrangian-particle-simulation (LES–LPS) of the planar jet with the characteristic length of the mixing volume of O(100η). Despite the large mixing volume, the MVM works well and decays the scalar variance in a rate close to the reference LES. The statistics in the LPS are very robust to the number of the particles used in the simulations and the computational grid size of the LES. Both in the turbulent core region and the intermittent region, the LPS predicts a scalar field well correlated to the LES.« less

Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

PubMed

Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J

2017-11-01

Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J.

2017-11-01

Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

Charge Behaviors around Oxide Device/Pseudo-Physiological Solution Interface with Molecular Dynamic Simulations

NASA Astrophysics Data System (ADS)

Maekawa, Yuki; Shibuta, Yasushi; Sakata, Toshiya

2013-12-01

In this study, we investigated the charge behaviors of ions and water molecules at the oxide device/pseudo-physiological solution interface by use of molecular dynamics (MD) simulations because the detection principle of semiconductor-based biosensors is based on the detection of charge density changes at the oxide sensing surface in physiological environments. In particular, we designed an alpha-quartz (100) surface with some charges corresponding to pH=5.5 so that the ionic behaviors for 500 mM each of Na+ and Cl- around the interface were calculated under the surface condition with charges, considering a real system. As a result of the simulation, we defined the region of Debye length from the calculated potential distribution, in which some parameters such as diffusion coefficient and the vibration of water molecules around the interface differed from those of the bulk solution. The elucidation of the solid/liquid interfacial behaviors by the simulation technique should deepen our understanding of the detection principle of semiconductor-based biosensors and will give guidelines for the design of a bio-interface in the field of biosensing technology, because they cannot be demonstrated experimentally.

A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA

PubMed Central

Lavery, Richard; Zakrzewska, Krystyna; Beveridge, David; Bishop, Thomas C.; Case, David A.; Cheatham, Thomas; Dixit, Surjit; Jayaram, B.; Lankas, Filip; Laughton, Charles; Maddocks, John H.; Michon, Alexis; Osman, Roman; Orozco, Modesto; Perez, Alberto; Singh, Tanya; Spackova, Nada; Sponer, Jiri

2010-01-01

It is well recognized that base sequence exerts a significant influence on the properties of DNA and plays a significant role in protein–DNA interactions vital for cellular processes. Understanding and predicting base sequence effects requires an extensive structural and dynamic dataset which is currently unavailable from experiment. A consortium of laboratories was consequently formed to obtain this information using molecular simulations. This article describes results providing information not only on all 10 unique base pair steps, but also on all possible nearest-neighbor effects on these steps. These results are derived from simulations of 50–100 ns on 39 different DNA oligomers in explicit solvent and using a physiological salt concentration. We demonstrate that the simulations are converged in terms of helical and backbone parameters. The results show that nearest-neighbor effects on base pair steps are very significant, implying that dinucleotide models are insufficient for predicting sequence-dependent behavior. Flanking base sequences can notably lead to base pair step parameters in dynamic equilibrium between two conformational sub-states. Although this study only provides limited data on next-nearest-neighbor effects, we suggest that such effects should be analyzed before attempting to predict the sequence-dependent behavior of DNA. PMID:19850719

Quantitative Analysis of the Molecular Dynamics of P3HT:PCBM Bulk Heterojunction.

PubMed

Guilbert, Anne A Y; Zbiri, Mohamed; Dunbar, Alan D F; Nelson, Jenny

2017-09-28

The optoelectronic properties of blends of conjugated polymers and small molecules are likely to be affected by the molecular dynamics of the active layer components. We study the dynamics of regioregular poly(3-hexylthiophene) (P3HT):phenyl-C61-butyric acid methyl ester (PCBM) blends using molecular dynamics (MD) simulation on time scales up to 50 ns and in a temperature range of 250-360 K. First, we compare the MD results with quasi-elastic neutron-scattering (QENS) measurements. Experiment and simulation give evidence of the vitrification of P3HT upon blending and the plasticization of PCBM by P3HT. Second, we reconstruct the QENS signal based on the independent simulations of the three phases constituting the complex microstructure of such blends. Finally, we found that P3HT chains tend to wrap around PCBM molecules in the amorphous mixture of P3HT and PCBM; this molecular interaction between P3HT and PCBM is likely to be responsible for the observed frustration of P3HT, the plasticization of PCBM, and the partial miscibility of P3HT and PCBM.

Molecular design of anticancer drug leads based on three-dimensional quantitative structure-activity relationship.

PubMed

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

2011-08-22

Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure-activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.

Modelling and enhanced molecular dynamics to steer structure-based drug discovery.

PubMed

Kalyaanamoorthy, Subha; Chen, Yi-Ping Phoebe

2014-05-01

The ever-increasing gap between the availabilities of the genome sequences and the crystal structures of proteins remains one of the significant challenges to the modern drug discovery efforts. The knowledge of structure-dynamics-functionalities of proteins is important in order to understand several key aspects of structure-based drug discovery, such as drug-protein interactions, drug binding and unbinding mechanisms and protein-protein interactions. This review presents a brief overview on the different state of the art computational approaches that are applied for protein structure modelling and molecular dynamics simulations of biological systems. We give an essence of how different enhanced sampling molecular dynamics approaches, together with regular molecular dynamics methods, assist in steering the structure based drug discovery processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Molecular Docking, Molecular Dynamics Simulations, Computational Screening to Design Quorum Sensing Inhibitors Targeting LuxP of Vibrio harveyi and Its Biological Evaluation.

PubMed

Rajamanikandan, Sundaraj; Jeyakanthan, Jeyaraman; Srinivasan, Pappu

2017-01-01

Quorum sensing (QS) plays an important role in the biofilm formation, production of virulence factors and stress responses in Vibrio harveyi. Therefore, interrupting QS is a possible approach to modulate bacterial behavior. In the present study, three docking protocols, such as Rigid Receptor Docking (RRD), Induced Fit Docking (IFD), and Quantum Polarized Ligand Docking (QPLD) were used to elucidate the binding mode of boronic acid derivatives into the binding pocket of LuxP protein in V. harveyi. Among the three docking protocols, IFD accurately predicted the correct binding mode of the studied inhibitors. Molecular dynamics (MD) simulations of the protein-ligand complexes indicates that the inter-molecular hydrogen bonds formed between the protein and ligand complex remains stable during the simulation time. Pharmacophore and shape-based virtual screening were performed to find selective and potent compounds from ChemBridge database. Five hit compounds were selected and subjected to IFD and MD simulations to validate the binding mode. In addition, enrichment calculation was performed to discriminate and separate active compounds from the inactive compounds. Based on the computational studies, the potent Bicyclo [2.2.1] hept-5-ene-2,3-dicarboxylic acid-2,6-dimethylpyridine 1-oxide (ChemBridge_5144368) was selected for in vitro assays. The compound exhibited dose dependent inhibition in bioluminescence and also inhibits biofilm formation in V. harveyi to the level of 64.25 %. The result from the study suggests that ChemBridge_5144368 could serve as an anti-quorum sensing molecule for V. harveyi.

Assessment of Real-Time Time-Dependent Density Functional Theory (RT-TDDFT) in Radiation Chemistry: Ionized Water Dimer.

PubMed

Chalabala, Jan; Uhlig, Frank; Slavíček, Petr

2018-03-29

Ionization in the condensed phase and molecular clusters leads to a complicated chain of processes with coupled electron-nuclear dynamics. It is difficult to describe such dynamics with conventional nonadiabatic molecular dynamics schemes since the number of states swiftly increases as the molecular system grows. It is therefore attractive to use a direct electron and nuclear propagation such as the real-time time-dependent density functional theory (RT-TDDFT). Here we report a RT-TDDFT benchmark study on simulations of singly and doubly ionized states of a water monomer and dimer as a prototype for more complex processes in a condensed phase. We employed the RT-TDDFT based Ehrenfest molecular dynamics with a generalized gradient approximate (GGA) functional and compared it with wave-function-based surface hopping (SH) simulations. We found that the initial dynamics of a singly HOMO ionized water dimer is similar for both the RT-TDDFT/GGA and the SH simulations but leads to completely different reaction channels on a longer time scale. This failure is attributed to the self-interaction error in the GGA functionals and it can be avoided by using hybrid functionals with large fraction of exact exchange (represented here by the BHandHLYP functional). The simulations of doubly ionized states are reasonably described already at the GGA level. This suggests that the RT-TDDFT/GGA method could describe processes following the autoionization processes such as Auger emission, while its applicability to more complex processes such as intermolecular Coulombic decay remains limited.

Molecular Docking and Molecular Dynamics to Identify a Novel Human Immunodeficiency Virus Inhibitor from Alkaloids of Toddalia asiatica.

PubMed

Priya, R; Sumitha, Rajendrarao; Doss, C George Priya; Rajasekaran, C; Babu, S; Seenivasan, R; Siva, R

2015-10-01

Acquired immunodeficiency syndrome caused by human immunodeficiency virus (HIV) is an immunosuppressive disease. Over the past decades, it has plagued human health due to the grave consequences in its harness. For this reason, anti-HIV agents are imperative, and the search for the same from natural resources would assure the safety. In this investigation we have performed molecular docking, molecular property prediction, drug-likeness score, and molecular dynamics (MD) simulation to develop a novel anti-HIV drug. We have screened 12 alkaloids from a medicinal plant Toddalia asiatica for its probabilistic binding with the active site of the HIV-1-reverse transcriptase (HIV-1-RT) domain (the major contributor to the onset of the disease). The docking results were evaluated based on free energies of binding (ΔG), and the results suggested toddanol, toddanone, and toddalenone to be potent inhibitors of HIV-1-RT. In addition, the alkaloids were subjected to molecular property prediction analysis. Toddanol and toddanone with more rotatable bonds were found to have a drug-likeness score of 0.23 and 0.11, respectively. These scores were comparable with the standard anti-HIV drug zidovudine with a model score 0.28. Finally, two characteristic protein-ligand complexes were exposed to MD simulation to determine the stability of the predicted conformations. The toddanol-RT complex showed higher stability and stronger H-bonds than toddanone-RT complex. Based on these observations, we firmly believe that the alkaloid toddanol could aid in efficient HIV-1 drug discovery. In the present study, the molecular docking and MD simulations are performed to explore the possible binding mode of HIV 1 RT with 12 alkaloids of T. asiatica. Molecular docking by AutoDock4 revealed three alkaloids toddanol, toddanone, and toddalenone with highest binding affinity towards HIV 1 RT. The drug likeness model score revealed a positive score for toddanol and toddanone which is comparable to the drug likeness score of the standard anti HIV drug zidovudine. Results from simulation analysis revealed that toddanol RT complex is more stable than toddanone RT complex inferring toddanol as a potential anti HIV drug molecule. Abbreviations used: HIV: Human immunodeficiency virus, HIV 1 RT: HIV 1 reverse transcriptase, RNase H: Ribonuclease H, MD: Molecular dynamics, PDB: Protein databank, RMSD: Root mean square deviation, RMSF: Root mean square fluctuation.

Measurement of contact-angle hysteresis for droplets on nanopillared surface and in the Cassie and Wenzel states: a molecular dynamics simulation study.

PubMed

Koishi, Takahiro; Yasuoka, Kenji; Fujikawa, Shigenori; Zeng, Xiao Cheng

2011-09-27

We perform large-scale molecular dynamics simulations to measure the contact-angle hysteresis for a nanodroplet of water placed on a nanopillared surface. The water droplet can be in either the Cassie state (droplet being on top of the nanopillared surface) or the Wenzel state (droplet being in contact with the bottom of nanopillar grooves). To measure the contact-angle hysteresis in a quantitative fashion, the molecular dynamics simulation is designed such that the number of water molecules in the droplets can be systematically varied, but the number of base nanopillars that are in direct contact with the droplets is fixed. We find that the contact-angle hysteresis for the droplet in the Cassie state is weaker than that in the Wenzel state. This conclusion is consistent with the experimental observation. We also test a different definition of the contact-angle hysteresis, which can be extended to estimate hysteresis between the Cassie and Wenzel state. The idea is motivated from the appearance of the hysteresis loop typically seen in computer simulation of the first-order phase transition, which stems from the metastability of a system in different thermodynamic states. Since the initial shape of the droplet can be controlled arbitrarily in the computer simulation, the number of base nanopillars that are in contact with the droplet can be controlled as well. We show that the measured contact-angle hysteresis according to the second definition is indeed very sensitive to the initial shape of the droplet. Nevertheless, the contact-angle hystereses measured based on the conventional and new definition seem converging in the large droplet limit. © 2011 American Chemical Society

Towards data warehousing and mining of protein unfolding simulation data.

PubMed

Berrar, Daniel; Stahl, Frederic; Silva, Candida; Rodrigues, J Rui; Brito, Rui M M; Dubitzky, Werner

2005-10-01

The prediction of protein structure and the precise understanding of protein folding and unfolding processes remains one of the greatest challenges in structural biology and bioinformatics. Computer simulations based on molecular dynamics (MD) are at the forefront of the effort to gain a deeper understanding of these complex processes. Currently, these MD simulations are usually on the order of tens of nanoseconds, generate a large amount of conformational data and are computationally expensive. More and more groups run such simulations and generate a myriad of data, which raises new challenges in managing and analyzing these data. Because the vast range of proteins researchers want to study and simulate, the computational effort needed to generate data, the large data volumes involved, and the different types of analyses scientists need to perform, it is desirable to provide a public repository allowing researchers to pool and share protein unfolding data. To adequately organize, manage, and analyze the data generated by unfolding simulation studies, we designed a data warehouse system that is embedded in a grid environment to facilitate the seamless sharing of available computer resources and thus enable many groups to share complex molecular dynamics simulations on a more regular basis. To gain insight into the conformational fluctuations and stability of the monomeric forms of the amyloidogenic protein transthyretin (TTR), molecular dynamics unfolding simulations of the monomer of human TTR have been conducted. Trajectory data and meta-data of the wild-type (WT) protein and the highly amyloidogenic variant L55P-TTR represent the test case for the data warehouse. Web and grid services, especially pre-defined data mining services that can run on or 'near' the data repository of the data warehouse, are likely to play a pivotal role in the analysis of molecular dynamics unfolding data.

Combined quantum mechanics and molecular mechanics simulation of Ca2+/ammonia solution based on the ONIOM-XS method: Octahedral coordination and implication to biology

NASA Astrophysics Data System (ADS)

Kerdcharoen, Teerakiat; Morokuma, Keiji

2003-05-01

An extension of the ONIOM (Own N-layered Integrated molecular Orbital and molecular Mechanics) method [M. Svensson, S. Humbel, R. D. J. Froese, T. Mutsubara, S. Sieber, and K. Morokuma, J. Phys. Chem. 100, 19357 (1996)] for simulation in the condensed phase, called ONIOM-XS (XS=eXtension to Solvation) [T. Kerdcharoen and K. Morokuma, Chem. Phys. Lett. 355, 257 (2002)], was applied to investigate the coordination of Ca2+ in liquid ammonia. A coordination number of 6 is found. Previous simulations based on pair potential or pair potential plus three-body correction gave values of 9 and 8.2, respectively. The new value is the same as the coordination number most frequently listed in the Cambridge Structural Database (CSD) and Protein Data Bank (PDB). N-Ca-N angular distribution reveals a near-octahedral coordination structure. Inclusion of many-body interactions (which amounts to 25% of the pair interactions) into the potential energy surface is essential for obtaining reasonable coordination number. Analyses of the metal coordination in water, water-ammonia mixture, and in proteins reveals that cation/ammonia solution can be used to approximate the coordination environment in proteins.

Diffusion-Based Model for Synaptic Molecular Communication Channel.

PubMed

Khan, Tooba; Bilgin, Bilgesu A; Akan, Ozgur B

2017-06-01

Computational methods have been extensively used to understand the underlying dynamics of molecular communication methods employed by nature. One very effective and popular approach is to utilize a Monte Carlo simulation. Although it is very reliable, this method can have a very high computational cost, which in some cases renders the simulation impractical. Therefore, in this paper, for the special case of an excitatory synaptic molecular communication channel, we present a novel mathematical model for the diffusion and binding of neurotransmitters that takes into account the effects of synaptic geometry in 3-D space and re-absorption of neurotransmitters by the transmitting neuron. Based on this model we develop a fast deterministic algorithm, which calculates expected value of the output of this channel, namely, the amplitude of excitatory postsynaptic potential (EPSP), for given synaptic parameters. We validate our algorithm by a Monte Carlo simulation, which shows total agreement between the results of the two methods. Finally, we utilize our model to quantify the effects of variation in synaptic parameters, such as position of release site, receptor density, size of postsynaptic density, diffusion coefficient, uptake probability, and number of neurotransmitters in a vesicle, on maximum number of bound receptors that directly affect the peak amplitude of EPSP.

Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide into a Membrane Bilayer

DTIC Science & Technology

2008-07-01

Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide into a Membrane Bilayer Mark A. Olson1, In...presents replica-exchange molecular dynamics simulations of the folding and insertion of a 16- residue Ebola virus fusion peptide into a membrane...separate calculated structures into conformational basins. 2.1 Simulation models Molecular dynamics simulations were performed using the all-atom

MSM/RD: Coupling Markov state models of molecular kinetics with reaction-diffusion simulations

NASA Astrophysics Data System (ADS)

Dibak, Manuel; del Razo, Mauricio J.; De Sancho, David; Schütte, Christof; Noé, Frank

2018-06-01

Molecular dynamics (MD) simulations can model the interactions between macromolecules with high spatiotemporal resolution but at a high computational cost. By combining high-throughput MD with Markov state models (MSMs), it is now possible to obtain long time-scale behavior of small to intermediate biomolecules and complexes. To model the interactions of many molecules at large length scales, particle-based reaction-diffusion (RD) simulations are more suitable but lack molecular detail. Thus, coupling MSMs and RD simulations (MSM/RD) would be highly desirable, as they could efficiently produce simulations at large time and length scales, while still conserving the characteristic features of the interactions observed at atomic detail. While such a coupling seems straightforward, fundamental questions are still open: Which definition of MSM states is suitable? Which protocol to merge and split RD particles in an association/dissociation reaction will conserve the correct bimolecular kinetics and thermodynamics? In this paper, we make the first step toward MSM/RD by laying out a general theory of coupling and proposing a first implementation for association/dissociation of a protein with a small ligand (A + B ⇌ C). Applications on a toy model and CO diffusion into the heme cavity of myoglobin are reported.

Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior, electrostatic and energetic analysis.

PubMed

Golebiowski, Jérôme; Antonczak, Serge; Di-Giorgio, Audrey; Condom, Roger; Cabrol-Bass, Daniel

2004-02-01

The dynamic behavior of the HCV IRES IIId domain is analyzed by means of a 2.6-ns molecular dynamics simulation, starting from an NMR structure. The simulation is carried out in explicit water with Na+ counterions, and particle-mesh Ewald summation is used for the electrostatic interactions. In this work, we analyze selected patterns of the helix that are crucial for IRES activity and that could be considered as targets for the intervention of inhibitors, such as the hexanucleotide terminal loop (more particularly its three consecutive guanines) and the loop-E motif. The simulation has allowed us to analyze the dynamics of the loop substructure and has revealed a behavior among the guanine bases that might explain the different role of the third guanine of the GGG triplet upon molecular recognition. The accessibility of the loop-E motif and the loop major and minor groove is also examined, as well as the effect of Na+ or Mg2+ counterion within the simulation. The electrostatic analysis reveals several ion pockets, not discussed in the experimental structure. The positions of these ions are useful for locating specific electrostatic recognition sites for potential inhibitor binding.

Estimation of Nanodiamond Surface Charge Density from Zeta Potential and Molecular Dynamics Simulations.

PubMed

Ge, Zhenpeng; Wang, Yi

2017-04-20

Molecular dynamics simulations of nanoparticles (NPs) are increasingly used to study their interactions with various biological macromolecules. Such simulations generally require detailed knowledge of the surface composition of the NP under investigation. Even for some well-characterized nanoparticles, however, this knowledge is not always available. An example is nanodiamond, a nanoscale diamond particle with surface dominated by oxygen-containing functional groups. In this work, we explore using the harmonic restraint method developed by Venable et al., to estimate the surface charge density (σ) of nanodiamonds. Based on the Gouy-Chapman theory, we convert the experimentally determined zeta potential of a nanodiamond to an effective charge density (σ eff ), and then use the latter to estimate σ via molecular dynamics simulations. Through scanning a series of nanodiamond models, we show that the above method provides a straightforward protocol to determine the surface charge density of relatively large (> ∼100 nm) NPs. Overall, our results suggest that despite certain limitation, the above protocol can be readily employed to guide the model construction for MD simulations, which is particularly useful when only limited experimental information on the NP surface composition is available to a modeler.

Ultra-Low Threshold Vertical-Cavity Surface-Emitting Lasers for USAF Applications

DTIC Science & Technology

2005-01-01

molecular beam epitaxy , semiconductors, finite element method, modeling and simulation, oxidation furnace 16. SECURITY CLASSIFICATION OF: 19a. NAME OF...Patterson Air Force Base). Device material growth was accomplished by means of molecular beam epitaxy (MBE) using a Varian GENII MBE system owned by the...grown by molecular beam epitaxy on a GaAs substrate. Vertical posts, with square and circular cross sections ranging in size from 5 to 40 microns

MDWeb and MDMoby: an integrated web-based platform for molecular dynamics simulations.

PubMed

Hospital, Adam; Andrio, Pau; Fenollosa, Carles; Cicin-Sain, Damjan; Orozco, Modesto; Gelpí, Josep Lluís

2012-05-01

MDWeb and MDMoby constitute a web-based platform to help access to molecular dynamics (MD) in the standard and high-throughput regime. The platform provides tools to prepare systems from PDB structures mimicking the procedures followed by human experts. It provides inputs and can send simulations for three of the most popular MD packages (Amber, NAMD and Gromacs). Tools for analysis of trajectories, either provided by the user or retrieved from our MoDEL database (http://mmb.pcb.ub.es/MoDEL) are also incorporated. The platform has two ways of access, a set of web-services based on the BioMoby framework (MDMoby), programmatically accessible and a web portal (MDWeb). http://mmb.irbbarcelona.org/MDWeb; additional information and methodology details can be found at the web site ( http://mmb.irbbarcelona.org/MDWeb/help.php)

Discovery of novel inhibitors of Mycobacterium tuberculosis MurG: homology modelling, structure based pharmacophore, molecular docking, and molecular dynamics simulations.

PubMed

Saxena, Shalini; Abdullah, Maaged; Sriram, Dharmarajan; Guruprasad, Lalitha

2017-10-17

MurG (Rv2153c) is a key player in the biosynthesis of the peptidoglycan layer in Mycobacterium tuberculosis (Mtb). This work is an attempt to highlight the structural and functional relationship of Mtb MurG, the three-dimensional (3D) structure of protein was constructed by homology modelling using Discovery Studio 3.5 software. The quality and consistency of generated model was assessed by PROCHECK, ProSA and ERRAT. Later, the model was optimized by molecular dynamics (MD) simulations and the optimized model complex with substrate Uridine-diphosphate-N-acetylglucosamine (UD1) facilitated us to employ structure-based virtual screening approach to obtain new hits from Asinex database using energy-optimized pharmacophore modelling (e-pharmacophore). The pharmacophore model was validated using enrichment calculations, and finally, validated model was employed for high-throughput virtual screening and molecular docking to identify novel Mtb MurG inhibitors. This study led to the identification of 10 potential compounds with good fitness, docking score, which make important interactions with the protein active site. The 25 ns MD simulations of three potential lead compounds with protein confirmed that the structure was stable and make several non-bonding interactions with amino acids, such as Leu290, Met310 and Asn167. Hence, we concluded that the identified compounds may act as new leads for the design of Mtb MurG inhibitors.

Multimillion atom simulations of dynamics of oxidation of an aluminum nanoparticle and nanoindentation on ceramics.

PubMed

Vashishta, Priya; Kalia, Rajiv K; Nakano, Aiichiro

2006-03-02

We have developed a first-principles-based hierarchical simulation framework, which seamlessly integrates (1) a quantum mechanical description based on the density functional theory (DFT), (2) multilevel molecular dynamics (MD) simulations based on a reactive force field (ReaxFF) that describes chemical reactions and polarization, a nonreactive force field that employs dynamic atomic charges, and an effective force field (EFF), and (3) an atomistically informed continuum model to reach macroscopic length scales. For scalable hierarchical simulations, we have developed parallel linear-scaling algorithms for (1) DFT calculation based on a divide-and-conquer algorithm on adaptive multigrids, (2) chemically reactive MD based on a fast ReaxFF (F-ReaxFF) algorithm, and (3) EFF-MD based on a space-time multiresolution MD (MRMD) algorithm. On 1920 Intel Itanium2 processors, we have demonstrated 1.4 million atom (0.12 trillion grid points) DFT, 0.56 billion atom F-ReaxFF, and 18.9 billion atom MRMD calculations, with parallel efficiency as high as 0.953. Through the use of these algorithms, multimillion atom MD simulations have been performed to study the oxidation of an aluminum nanoparticle. Structural and dynamic correlations in the oxide region are calculated as well as the evolution of charges, surface oxide thickness, diffusivities of atoms, and local stresses. In the microcanonical ensemble, the oxidizing reaction becomes explosive in both molecular and atomic oxygen environments, due to the enormous energy release associated with Al-O bonding. In the canonical ensemble, an amorphous oxide layer of a thickness of approximately 40 angstroms is formed after 466 ps, in good agreement with experiments. Simulations have been performed to study nanoindentation on crystalline, amorphous, and nanocrystalline silicon nitride and silicon carbide. Simulation on nanocrystalline silicon carbide reveals unusual deformation mechanisms in brittle nanophase materials, due to coexistence of brittle grains and soft amorphous-like grain boundary phases. Simulations predict a crossover from intergranular continuous deformation to intragrain discrete deformation at a critical indentation depth.

Molecular-dynamics Simulation-based Cohesive Zone Representation of Intergranular Fracture Processes in Aluminum

NASA Technical Reports Server (NTRS)

Yamakov, Vesselin I.; Saether, Erik; Phillips, Dawn R.; Glaessgen, Edward H.

2006-01-01

A traction-displacement relationship that may be embedded into a cohesive zone model for microscale problems of intergranular fracture is extracted from atomistic molecular-dynamics simulations. A molecular-dynamics model for crack propagation under steady-state conditions is developed to analyze intergranular fracture along a flat 99 [1 1 0] symmetric tilt grain boundary in aluminum. Under hydrostatic tensile load, the simulation reveals asymmetric crack propagation in the two opposite directions along the grain boundary. In one direction, the crack propagates in a brittle manner by cleavage with very little or no dislocation emission, and in the other direction, the propagation is ductile through the mechanism of deformation twinning. This behavior is consistent with the Rice criterion for cleavage vs. dislocation blunting transition at the crack tip. The preference for twinning to dislocation slip is in agreement with the predictions of the Tadmor and Hai criterion. A comparison with finite element calculations shows that while the stress field around the brittle crack tip follows the expected elastic solution for the given boundary conditions of the model, the stress field around the twinning crack tip has a strong plastic contribution. Through the definition of a Cohesive-Zone-Volume-Element an atomistic analog to a continuum cohesive zone model element - the results from the molecular-dynamics simulation are recast to obtain an average continuum traction-displacement relationship to represent cohesive zone interaction along a characteristic length of the grain boundary interface for the cases of ductile and brittle decohesion. Keywords: Crack-tip plasticity; Cohesive zone model; Grain boundary decohesion; Intergranular fracture; Molecular-dynamics simulation

Multiscale investigation of chemical interference in proteins

NASA Astrophysics Data System (ADS)

Samiotakis, Antonios; Homouz, Dirar; Cheung, Margaret S.

2010-05-01

We developed a multiscale approach (MultiSCAAL) that integrates the potential of mean force obtained from all-atomistic molecular dynamics simulations with a knowledge-based energy function for coarse-grained molecular simulations in better exploring the energy landscape of a small protein under chemical interference such as chemical denaturation. An excessive amount of water molecules in all-atomistic molecular dynamics simulations often negatively impacts the sampling efficiency of some advanced sampling techniques such as the replica exchange method and it makes the investigation of chemical interferences on protein dynamics difficult. Thus, there is a need to develop an effective strategy that focuses on sampling structural changes in protein conformations rather than solvent molecule fluctuations. In this work, we address this issue by devising a multiscale simulation scheme (MultiSCAAL) that bridges the gap between all-atomistic molecular dynamics simulation and coarse-grained molecular simulation. The two key features of this scheme are the Boltzmann inversion and a protein atomistic reconstruction method we previously developed (SCAAL). Using MultiSCAAL, we were able to enhance the sampling efficiency of proteins solvated by explicit water molecules. Our method has been tested on the folding energy landscape of a small protein Trp-cage with explicit solvent under 8M urea using both the all-atomistic replica exchange molecular dynamics and MultiSCAAL. We compared computational analyses on ensemble conformations of Trp-cage with its available experimental NOE distances. The analysis demonstrated that conformations explored by MultiSCAAL better agree with the ones probed in the experiments because it can effectively capture the changes in side-chain orientations that can flip out of the hydrophobic pocket in the presence of urea and water molecules. In this regard, MultiSCAAL is a promising and effective sampling scheme for investigating chemical interference which presents a great challenge when modeling protein interactions in vivo.

Validation of Molecular Dynamics Simulations for Prediction of Three-Dimensional Structures of Small Proteins.

PubMed

Kato, Koichi; Nakayoshi, Tomoki; Fukuyoshi, Shuichi; Kurimoto, Eiji; Oda, Akifumi

2017-10-12

Although various higher-order protein structure prediction methods have been developed, almost all of them were developed based on the three-dimensional (3D) structure information of known proteins. Here we predicted the short protein structures by molecular dynamics (MD) simulations in which only Newton's equations of motion were used and 3D structural information of known proteins was not required. To evaluate the ability of MD simulationto predict protein structures, we calculated seven short test protein (10-46 residues) in the denatured state and compared their predicted and experimental structures. The predicted structure for Trp-cage (20 residues) was close to the experimental structure by 200-ns MD simulation. For proteins shorter or longer than Trp-cage, root-mean square deviation values were larger than those for Trp-cage. However, secondary structures could be reproduced by MD simulations for proteins with 10-34 residues. Simulations by replica exchange MD were performed, but the results were similar to those from normal MD simulations. These results suggest that normal MD simulations can roughly predict short protein structures and 200-ns simulations are frequently sufficient for estimating the secondary structures of protein (approximately 20 residues). Structural prediction method using only fundamental physical laws are useful for investigating non-natural proteins, such as primitive proteins and artificial proteins for peptide-based drug delivery systems.

3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer.

PubMed

Chaube, Udit; Chhatbar, Dhara; Bhatt, Hardik

2016-02-01

According to WHO statistics, lung cancer is one of the leading causes of death among all other types of cancer. Many genes get mutated in lung cancer but involvement of EGFR and KRAS are more common. Unavailability of drugs or resistance to the available drugs is the major problem in the treatment of lung cancer. In the present research, mTOR was selected as an alternative target for the treatment of lung cancer which involves PI3K/AKT/mTOR pathway. 28 synthetic mTOR inhibitors were selected from the literature. Ligand based approach (CoMFA and CoMSIA) and structure based approach (molecular dynamics simulations assisted molecular docking study) were applied for the identification of important features of benzoxazepine moiety, responsible for mTOR inhibition. Three different alignments were tried to obtain best QSAR model, of which, distil was found to be the best method, as it gave good statistical results. In CoMFA, Leave One Out (LOO) cross validated coefficients (q(2)), conventional coefficient (r(2)) and predicted correlation coefficient (r(2)pred) values were found to be 0.615, 0.990 and 0.930, respectively. Similarly in CoMSIA, q(2), r(2)ncv and r(2)pred values were found to be 0.748, 0.986 and 0.933, respectively. Molecular dynamics and simulations study revealed that B-chain of mTOR protein was stable at and above 500 FS with respect to temperature (at and above 298 K), Potential energy (at and above 7669.72 kJ/mol) and kinetic energy (at and above 4009.77 kJ/mol). Molecular docking study was performed on simulated protein of mTOR which helped to correlate interactions of amino acids surrounded to the ligand with contour maps generated by QSAR method. Important features of benzoxazepine were identified by contour maps and molecular docking study which would be useful to design novel molecules as mTOR inhibitors for the treatment of lung cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

gRINN: a tool for calculation of residue interaction energies and protein energy network analysis of molecular dynamics simulations.

PubMed

Serçinoglu, Onur; Ozbek, Pemra

2018-05-25

Atomistic molecular dynamics (MD) simulations generate a wealth of information related to the dynamics of proteins. If properly analyzed, this information can lead to new insights regarding protein function and assist wet-lab experiments. Aiming to identify interactions between individual amino acid residues and the role played by each in the context of MD simulations, we present a stand-alone software called gRINN (get Residue Interaction eNergies and Networks). gRINN features graphical user interfaces (GUIs) and a command-line interface for generating and analyzing pairwise residue interaction energies and energy correlations from protein MD simulation trajectories. gRINN utilizes the features of NAMD or GROMACS MD simulation packages and automatizes the steps necessary to extract residue-residue interaction energies from user-supplied simulation trajectories, greatly simplifying the analysis for the end-user. A GUI, including an embedded molecular viewer, is provided for visualization of interaction energy time-series, distributions, an interaction energy matrix, interaction energy correlations and a residue correlation matrix. gRINN additionally offers construction and analysis of Protein Energy Networks, providing residue-based metrics such as degrees, betweenness-centralities, closeness centralities as well as shortest path analysis. gRINN is free and open to all users without login requirement at http://grinn.readthedocs.io.

Reduced Order Models for Reactions of Energetic Materials

NASA Astrophysics Data System (ADS)

Kober, Edward

The formulation of reduced order models for the reaction chemistry of energetic materials under high pressures is needed for the development of mesoscale models in the areas of initiation, deflagration and detonation. Phenomenologically, 4-8 step models have been formulated from the analysis of cook-off data by analyzing the temperature rise of heated samples. Reactive molecular dynamics simulations have been used to simulate many of these processes, but reducing the results of those simulations to simple models has not been achieved. Typically, these efforts have focused on identifying molecular species and detailing specific chemical reactions. An alternative approach is presented here that is based on identifying the coordination geometries of each atom in the simulation and tracking classes of reactions by correlated changes in these geometries. Here, every atom and type of reaction is documented for every time step; no information is lost from unsuccessful molecular identification. Principal Component Analysis methods can then be used to map out the effective chemical reaction steps. For HMX and TATB decompositions simulated with ReaxFF, 90% of the data can be explained by 4-6 steps, generating models similar to those from the cook-off analysis. By performing these simulations at a variety of temperatures and pressures, both the activation and reaction energies and volumes can then be extracted.

A Force Balanced Fragmentation Method for ab Initio Molecular Dynamic Simulation of Protein.

PubMed

Xu, Mingyuan; Zhu, Tong; Zhang, John Z H

2018-01-01

A force balanced generalized molecular fractionation with conjugate caps (FB-GMFCC) method is proposed for ab initio molecular dynamic simulation of proteins. In this approach, the energy of the protein is computed by a linear combination of the QM energies of individual residues and molecular fragments that account for the two-body interaction of hydrogen bond between backbone peptides. The atomic forces on the caped H atoms were corrected to conserve the total force of the protein. Using this approach, ab initio molecular dynamic simulation of an Ace-(ALA) 9 -NME linear peptide showed the conservation of the total energy of the system throughout the simulation. Further a more robust 110 ps ab initio molecular dynamic simulation was performed for a protein with 56 residues and 862 atoms in explicit water. Compared with the classical force field, the ab initio molecular dynamic simulations gave better description of the geometry of peptide bonds. Although further development is still needed, the current approach is highly efficient, trivially parallel, and can be applied to ab initio molecular dynamic simulation study of large proteins.

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

PubMed

Riniker, Sereina

2018-03-26

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

Hybrid particle-field molecular dynamics simulation for polyelectrolyte systems.

PubMed

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

2016-04-14

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

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.

Organization of the 1993 Optical Remote Sensing Topical Meeteing held in Salt Lake City, UT, 8-12 Mar 1993

DTIC Science & Technology

1994-06-01

S.C. 1992. Simulated Retrieval of Atmospheric Ozone from Aircraft ,A Interferometer Observations. Masters 7.5 thesis . University of Wisconsin...laser-based sensor system for long-path ab- presented. (p. 72) sorption measurements of atmospheric concentration and near-ir molecular spectral...performance of satellite- borne lidar-based wind sensors. (p. 247) 2:30 pm-3:00 pm COFFEE BREAK 11:20 am WB5 Simulation of space-based Doppler lidar wind SALON

Excess electron localization in solvated DNA bases.

PubMed

Smyth, Maeve; Kohanoff, Jorge

2011-06-10

We present a first-principles molecular dynamics study of an excess electron in condensed phase models of solvated DNA bases. Calculations on increasingly large microsolvated clusters taken from liquid phase simulations show that adiabatic electron affinities increase systematically upon solvation, as for optimized gas-phase geometries. Dynamical simulations after vertical attachment indicate that the excess electron, which is initially found delocalized, localizes around the nucleobases within a 15 fs time scale. This transition requires small rearrangements in the geometry of the bases.

Excess Electron Localization in Solvated DNA Bases

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

Smyth, Maeve; Kohanoff, Jorge

2011-06-10

We present a first-principles molecular dynamics study of an excess electron in condensed phase models of solvated DNA bases. Calculations on increasingly large microsolvated clusters taken from liquid phase simulations show that adiabatic electron affinities increase systematically upon solvation, as for optimized gas-phase geometries. Dynamical simulations after vertical attachment indicate that the excess electron, which is initially found delocalized, localizes around the nucleobases within a 15 fs time scale. This transition requires small rearrangements in the geometry of the bases.

An atomistic simulation scheme for modeling crystal formation from solution.

PubMed

Kawska, Agnieszka; Brickmann, Jürgen; Kniep, Rüdiger; Hochrein, Oliver; Zahn, Dirk

2006-01-14

We present an atomistic simulation scheme for investigating crystal growth from solution. Molecular-dynamics simulation studies of such processes typically suffer from considerable limitations concerning both system size and simulation times. In our method this time-length scale problem is circumvented by an iterative scheme which combines a Monte Carlo-type approach for the identification of ion adsorption sites and, after each growth step, structural optimization of the ion cluster and the solvent by means of molecular-dynamics simulation runs. An important approximation of our method is based on assuming full structural relaxation of the aggregates between each of the growth steps. This concept only holds for compounds of low solubility. To illustrate our method we studied CaF2 aggregate growth from aqueous solution, which may be taken as prototypes for compounds of very low solubility. The limitations of our simulation scheme are illustrated by the example of NaCl aggregation from aqueous solution, which corresponds to a solute/solvent combination of very high salt solubility.

Cooling rate effects in sodium silicate glasses: Bridging the gap between molecular dynamics simulations and experiments

NASA Astrophysics Data System (ADS)

Li, Xin; Song, Weiying; Yang, Kai; Krishnan, N. M. Anoop; Wang, Bu; Smedskjaer, Morten M.; Mauro, John C.; Sant, Gaurav; Balonis, Magdalena; Bauchy, Mathieu

2017-08-01

Although molecular dynamics (MD) simulations are commonly used to predict the structure and properties of glasses, they are intrinsically limited to short time scales, necessitating the use of fast cooling rates. It is therefore challenging to compare results from MD simulations to experimental results for glasses cooled on typical laboratory time scales. Based on MD simulations of a sodium silicate glass with varying cooling rate (from 0.01 to 100 K/ps), here we show that thermal history primarily affects the medium-range order structure, while the short-range order is largely unaffected over the range of cooling rates simulated. This results in a decoupling between the enthalpy and volume relaxation functions, where the enthalpy quickly plateaus as the cooling rate decreases, whereas density exhibits a slower relaxation. Finally, we show that, using the proper extrapolation method, the outcomes of MD simulations can be meaningfully compared to experimental values when extrapolated to slower cooling rates.

Next generation extended Lagrangian first principles molecular dynamics

NASA Astrophysics Data System (ADS)

Niklasson, Anders M. N.

2017-08-01

Extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] is formulated for general Hohenberg-Kohn density-functional theory and compared with the extended Lagrangian framework of first principles molecular dynamics by Car and Parrinello [Phys. Rev. Lett. 55, 2471 (1985)]. It is shown how extended Lagrangian Born-Oppenheimer molecular dynamics overcomes several shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while improving or maintaining important features of Car-Parrinello simulations. The accuracy of the electronic degrees of freedom in extended Lagrangian Born-Oppenheimer molecular dynamics, with respect to the exact Born-Oppenheimer solution, is of second-order in the size of the integration time step and of fourth order in the potential energy surface. Improved stability over recent formulations of extended Lagrangian Born-Oppenheimer molecular dynamics is achieved by generalizing the theory to finite temperature ensembles, using fractional occupation numbers in the calculation of the inner-product kernel of the extended harmonic oscillator that appears as a preconditioner in the electronic equations of motion. Material systems that normally exhibit slow self-consistent field convergence can be simulated using integration time steps of the same order as in direct Born-Oppenheimer molecular dynamics, but without the requirement of an iterative, non-linear electronic ground-state optimization prior to the force evaluations and without a systematic drift in the total energy. In combination with proposed low-rank and on the fly updates of the kernel, this formulation provides an efficient and general framework for quantum-based Born-Oppenheimer molecular dynamics simulations.

Next generation extended Lagrangian first principles molecular dynamics.

PubMed

Niklasson, Anders M N

2017-08-07

Extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] is formulated for general Hohenberg-Kohn density-functional theory and compared with the extended Lagrangian framework of first principles molecular dynamics by Car and Parrinello [Phys. Rev. Lett. 55, 2471 (1985)]. It is shown how extended Lagrangian Born-Oppenheimer molecular dynamics overcomes several shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while improving or maintaining important features of Car-Parrinello simulations. The accuracy of the electronic degrees of freedom in extended Lagrangian Born-Oppenheimer molecular dynamics, with respect to the exact Born-Oppenheimer solution, is of second-order in the size of the integration time step and of fourth order in the potential energy surface. Improved stability over recent formulations of extended Lagrangian Born-Oppenheimer molecular dynamics is achieved by generalizing the theory to finite temperature ensembles, using fractional occupation numbers in the calculation of the inner-product kernel of the extended harmonic oscillator that appears as a preconditioner in the electronic equations of motion. Material systems that normally exhibit slow self-consistent field convergence can be simulated using integration time steps of the same order as in direct Born-Oppenheimer molecular dynamics, but without the requirement of an iterative, non-linear electronic ground-state optimization prior to the force evaluations and without a systematic drift in the total energy. In combination with proposed low-rank and on the fly updates of the kernel, this formulation provides an efficient and general framework for quantum-based Born-Oppenheimer molecular dynamics simulations.

Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations

PubMed Central

Fogolari, Federico; Corazza, Alessandra; Fortuna, Sara; Soler, Miguel Angel; VanSchouwen, Bryan; Brancolini, Giorgia; Corni, Stefano; Melacini, Giuseppe; Esposito, Gennaro

2015-01-01

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy);the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic. PMID:26177039

Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations.

PubMed

Fogolari, Federico; Corazza, Alessandra; Fortuna, Sara; Soler, Miguel Angel; VanSchouwen, Bryan; Brancolini, Giorgia; Corni, Stefano; Melacini, Giuseppe; Esposito, Gennaro

2015-01-01

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy);the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic.

POLYVIEW-MM: web-based platform for animation and analysis of molecular simulations

PubMed Central

Porollo, Aleksey; Meller, Jaroslaw

2010-01-01

Molecular simulations offer important mechanistic and functional clues in studies of proteins and other macromolecules. However, interpreting the results of such simulations increasingly requires tools that can combine information from multiple structural databases and other web resources, and provide highly integrated and versatile analysis tools. Here, we present a new web server that integrates high-quality animation of molecular motion (MM) with structural and functional analysis of macromolecules. The new tool, dubbed POLYVIEW-MM, enables animation of trajectories generated by molecular dynamics and related simulation techniques, as well as visualization of alternative conformers, e.g. obtained as a result of protein structure prediction methods or small molecule docking. To facilitate structural analysis, POLYVIEW-MM combines interactive view and analysis of conformational changes using Jmol and its tailored extensions, publication quality animation using PyMol, and customizable 2D summary plots that provide an overview of MM, e.g. in terms of changes in secondary structure states and relative solvent accessibility of individual residues in proteins. Furthermore, POLYVIEW-MM integrates visualization with various structural annotations, including automated mapping of known inter-action sites from structural homologs, mapping of cavities and ligand binding sites, transmembrane regions and protein domains. URL: http://polyview.cchmc.org/conform.html. PMID:20504857

Hamiltonian replica exchange combined with elastic network analysis to enhance global domain motions in atomistic molecular dynamics simulations.

PubMed

Ostermeir, Katja; Zacharias, Martin

2014-12-01

Coarse-grained elastic network models (ENM) of proteins offer a low-resolution representation of protein dynamics and directions of global mobility. A Hamiltonian-replica exchange molecular dynamics (H-REMD) approach has been developed that combines information extracted from an ENM analysis with atomistic explicit solvent MD simulations. Based on a set of centers representing rigid segments (centroids) of a protein, a distance-dependent biasing potential is constructed by means of an ENM analysis to promote and guide centroid/domain rearrangements. The biasing potentials are added with different magnitude to the force field description of the MD simulation along the replicas with one reference replica under the control of the original force field. The magnitude and the form of the biasing potentials are adapted during the simulation based on the average sampled conformation to reach a near constant biasing in each replica after equilibration. This allows for canonical sampling of conformational states in each replica. The application of the methodology to a two-domain segment of the glycoprotein 130 and to the protein cyanovirin-N indicates significantly enhanced global domain motions and improved conformational sampling compared with conventional MD simulations. © 2014 Wiley Periodicals, Inc.

Revisiting imidazolium based ionic liquids: Effect of the conformation bias of the [NTf2] anion studied by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Neumann, Jan; Golub, Benjamin; Odebrecht, Lisa-Marie; Ludwig, Ralf; Paschek, Dietmar

2018-05-01

We study ionic liquids composed of 1-alkyl-3-methylimidazolium cations and bis(trifluoromethyl-sulfonyl)imide anions ([CnMIm][NTf2]) with varying chain-length n = 2, 4, 6, 8 by using molecular dynamics simulations. We show that a reparametrization of the dihedral potentials as well as charges of the [NTf2] anion leads to an improvement of the force field model introduced by Köddermann, Paschek, and Ludwig [ChemPhysChem 8, 2464 (2007)] (KPL-force field). A crucial advantage of the new parameter set is that the minimum energy conformations of the anion (trans and gauche), as deduced from ab initio calculations and Raman experiments, are now both well represented by our model. In addition, the results for [CnMIm][NTf2] show that this modification leads to an even better agreement between experiment and molecular dynamics simulation as demonstrated for densities, diffusion coefficients, vaporization enthalpies, reorientational correlation times, and viscosities. Even though we focused on a better representation of the anion conformation, also the alkyl chain-length dependence of the cation behaves closer to the experiment. We strongly encourage to use the new NGOLP (Neumann, Golub, Odebrecht, Ludwig, Paschek) force field for the [NTf2] anion instead of the earlier KPL parameter set for computer simulations aiming to describe the thermodynamics, dynamics, and also structure of imidazolium-based ionic liquids.

Investigation of arc repressor DNA-binding specificity by comparative molecular dynamics simulations.

PubMed

Song, Wei; Guo, Jun-Tao

2015-01-01

Transcription factors regulate gene expression through binding to specific DNA sequences. How transcription factors achieve high binding specificity is still not well understood. In this paper, we investigated the role of protein flexibility in protein-DNA-binding specificity by comparative molecular dynamics (MD) simulations. Protein flexibility has been considered as a key factor in molecular recognition, which is intrinsically a dynamic process involving fine structural fitting between binding components. In this study, we performed comparative MD simulations on wild-type and F10V mutant P22 Arc repressor in both free and complex conformations. The F10V mutant has lower DNA-binding specificity though both the bound and unbound main-chain structures between the wild-type and F10V mutant Arc are highly similar. We found that the DNA-binding motif of wild-type Arc is structurally more flexible than the F10V mutant in the unbound state, especially for the six DNA base-contacting residues in each dimer. We demonstrated that the flexible side chains of wild-type Arc lead to a higher DNA-binding specificity through forming more hydrogen bonds with DNA bases upon binding. Our simulations also showed a possible conformational selection mechanism for Arc-DNA binding. These results indicate the important roles of protein flexibility and dynamic properties in protein-DNA-binding specificity.

Structure, thermodynamic and transport properties of imidazolium-based bis(trifluoromethylsulfonyl)imide ionic liquids from molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Androulaki, Eleni; Vergadou, Niki; Ramos, Javier; Economou, Ioannis G.

2012-06-01

Molecular dynamics (MD) simulations have been performed in order to investigate the properties of [C n mim+][Tf2N-] (n = 4, 8, 12) ionic liquids (ILs) in a wide temperature range (298.15-498.15 K) and at atmospheric pressure (1 bar). A previously developed methodology for the calculation of the charge distribution that incorporates ab initio quantum mechanical calculations based on density functional theory (DFT) was used to calculate the partial charges for the classical molecular simulations. The wide range of time scales that characterize the segmental dynamics of these ILs, especially at low temperatures, required very long MD simulations, on the order of several tens of nanoseconds, to calculate the thermodynamic (density, thermal expansion, isothermal compressibility), structural (radial distribution functions between the centers of mass of ions and between individual sites, radial-angular distribution functions) and dynamic (relaxation times of the reorientation of the bonds and the torsion angles, self-diffusion coefficients, shear viscosity) properties. The influence of the temperature and the cation's alkyl chain length on the above-mentioned properties was thoroughly investigated. The calculated thermodynamic (primary and derivative) and structural properties are in good agreement with the experimental data, while the extremely sluggish dynamics of the ILs under study renders the calculation of their transport properties a very complicated and challenging task, especially at low temperatures.

The Influence of 150-Cavity Binders on the Dynamics of Influenza A Neuraminidases as Revealed by Molecular Dynamics Simulations and Combined Clustering

PubMed Central

Greenway, Kyle T.; LeGresley, Eric B.; Pinto, B. Mario

2013-01-01

Neuraminidase inhibitors are the main pharmaceutical agents employed for treatments of influenza infections. The neuraminidase structures typically exhibit a 150-cavity, an exposed pocket that is adjacent to the catalytic site. This site offers promising additional contact points for improving potency of existing pharmaceuticals, as well as generating entirely new candidate inhibitors. Several inhibitors based on known compounds and designed to interact with 150-cavity residues have been reported. However, the dynamics of any of these inhibitors remains unstudied and their viability remains unknown. This work reports the outcome of long-term, all-atom molecular dynamics simulations of four such inhibitors, along with three standard inhibitors for comparison. Each is studied in complex with four representative neuraminidase structures, which are also simulated in the absence of ligands for comparison, resulting in a total simulation time of 9.6µs. Our results demonstrate that standard inhibitors characteristically reduce the mobility of these dynamic proteins, while the 150-binders do not, instead giving rise to many unique conformations. We further describe an improved RMSD-based clustering technique that isolates these conformations – the structures of which are provided to facilitate future molecular docking studies – and reveals their interdependence. We find that this approach confers many advantages over previously described techniques, and the implications for rational drug design are discussed. PMID:23544106

The influence of 150-cavity binders on the dynamics of influenza A neuraminidases as revealed by molecular dynamics simulations and combined clustering.

PubMed

Greenway, Kyle T; LeGresley, Eric B; Pinto, B Mario

2013-01-01

Neuraminidase inhibitors are the main pharmaceutical agents employed for treatments of influenza infections. The neuraminidase structures typically exhibit a 150-cavity, an exposed pocket that is adjacent to the catalytic site. This site offers promising additional contact points for improving potency of existing pharmaceuticals, as well as generating entirely new candidate inhibitors. Several inhibitors based on known compounds and designed to interact with 150-cavity residues have been reported. However, the dynamics of any of these inhibitors remains unstudied and their viability remains unknown. This work reports the outcome of long-term, all-atom molecular dynamics simulations of four such inhibitors, along with three standard inhibitors for comparison. Each is studied in complex with four representative neuraminidase structures, which are also simulated in the absence of ligands for comparison, resulting in a total simulation time of 9.6 µs. Our results demonstrate that standard inhibitors characteristically reduce the mobility of these dynamic proteins, while the 150-binders do not, instead giving rise to many unique conformations. We further describe an improved RMSD-based clustering technique that isolates these conformations--the structures of which are provided to facilitate future molecular docking studies--and reveals their interdependence. We find that this approach confers many advantages over previously described techniques, and the implications for rational drug design are discussed.

Carbon Nanotube Based Molecular Electronics and Motors: A View from Classical and Quantum Dynamics Simulations

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Saini, Subhash (Technical Monitor)

1998-01-01

The tubular forms of fullerenes popularly known as carbon nanotubes are experimentally produced as single-, multiwall, and rope configurations. The nanotubes and nanoropes have shown to exhibit unusual mechanical and electronic properties. The single wall nanotubes exhibit both semiconducting and metallic behavior. In short undefected lengths they are the known strongest fibers which are unbreakable even when bent in half. Grown in ropes their tensile strength is approximately 100 times greater than steel at only one sixth the weight. Employing large scale classical and quantum molecular dynamics simulations we will explore the use of carbon nanotubes and carbon nanotube junctions in 2-, 3-, and 4-point molecular electronic device components, dynamic strength characterization for compressive, bending and torsional strains, and chemical functionalization for possible use in a nanoscale molecular motor. The above is an unclassified material produced for non-competitive basic research in the nanotechnology area.

Thermodynamic properties for applications in chemical industry via classical force fields.

PubMed

Guevara-Carrion, Gabriela; Hasse, Hans; Vrabec, Jadran

2012-01-01

Thermodynamic properties of fluids are of key importance for the chemical industry. Presently, the fluid property models used in process design and optimization are mostly equations of state or G (E) models, which are parameterized using experimental data. Molecular modeling and simulation based on classical force fields is a promising alternative route, which in many cases reasonably complements the well established methods. This chapter gives an introduction to the state-of-the-art in this field regarding molecular models, simulation methods, and tools. Attention is given to the way modeling and simulation on the scale of molecular force fields interact with other scales, which is mainly by parameter inheritance. Parameters for molecular force fields are determined both bottom-up from quantum chemistry and top-down from experimental data. Commonly used functional forms for describing the intra- and intermolecular interactions are presented. Several approaches for ab initio to empirical force field parameterization are discussed. Some transferable force field families, which are frequently used in chemical engineering applications, are described. Furthermore, some examples of force fields that were parameterized for specific molecules are given. Molecular dynamics and Monte Carlo methods for the calculation of transport properties and vapor-liquid equilibria are introduced. Two case studies are presented. First, using liquid ammonia as an example, the capabilities of semi-empirical force fields, parameterized on the basis of quantum chemical information and experimental data, are discussed with respect to thermodynamic properties that are relevant for the chemical industry. Second, the ability of molecular simulation methods to describe accurately vapor-liquid equilibrium properties of binary mixtures containing CO(2) is shown.

Virtual Transgenics: Using a Molecular Biology Simulation to Impact Student Academic Achievement and Attitudes

ERIC Educational Resources Information Center

Shegog, Ross; Lazarus, Melanie M.; Murray, Nancy G.; Diamond, Pamela M.; Sessions, Nathalie; Zsigmond, Eva

2012-01-01

The transgenic mouse model is useful for studying the causes and potential cures for human genetic diseases. Exposing high school biology students to laboratory experience in developing transgenic animal models is logistically prohibitive. Computer-based simulation, however, offers this potential in addition to advantages of fidelity and reach.…

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations

PubMed Central

Ahlstrom, Logan S.; Vorontsov, Ivan I.; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations. PMID:28107510

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations.

PubMed

Ahlstrom, Logan S; Vorontsov, Ivan I; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.

Fixman compensating potential for general branched molecules

NASA Astrophysics Data System (ADS)

Jain, Abhinandan; Kandel, Saugat; Wagner, Jeffrey; Larsen, Adrien; Vaidehi, Nagarajan

2013-12-01

The technique of constraining high frequency modes of molecular motion is an effective way to increase simulation time scale and improve conformational sampling in molecular dynamics simulations. However, it has been shown that constraints on higher frequency modes such as bond lengths and bond angles stiffen the molecular model, thereby introducing systematic biases in the statistical behavior of the simulations. Fixman proposed a compensating potential to remove such biases in the thermodynamic and kinetic properties calculated from dynamics simulations. Previous implementations of the Fixman potential have been limited to only short serial chain systems. In this paper, we present a spatial operator algebra based algorithm to calculate the Fixman potential and its gradient within constrained dynamics simulations for branched topology molecules of any size. Our numerical studies on molecules of increasing complexity validate our algorithm by demonstrating recovery of the dihedral angle probability distribution function for systems that range in complexity from serial chains to protein molecules. We observe that the Fixman compensating potential recovers the free energy surface of a serial chain polymer, thus annulling the biases caused by constraining the bond lengths and bond angles. The inclusion of Fixman potential entails only a modest increase in the computational cost in these simulations. We believe that this work represents the first instance where the Fixman potential has been used for general branched systems, and establishes the viability for its use in constrained dynamics simulations of proteins and other macromolecules.

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

NanoDesign: Concepts and Software for a Nanotechnology Based on Functionalized Fullerenes

NASA Technical Reports Server (NTRS)

Globus, Al; Jaffe, Richard; Chancellor, Marisa K. (Technical Monitor)

1996-01-01

Eric Drexler has proposed a hypothetical nanotechnology based on diamond and investigated the properties of such molecular systems. While attractive, diamonoid nanotechnology is not physically accessible with straightforward extensions of current laboratory techniques. We propose a nanotechnology based on functionalized fullerenes and investigate carbon nanotube based gears with teeth added via a benzyne reaction known to occur with C60. The gears are single-walled carbon nanotubes with appended coenzyme groups for teeth. Fullerenes are in widespread laboratory use and can be functionalized in many ways. Companion papers computationally demonstrate the properties of these gears (they appear to work) and the accessibility of the benzyne/nanotube reaction. This paper describes the molecular design techniques and rationale as well as the software that implements these design techniques. The software is a set of persistent C++ objects controlled by TCL command scripts. The c++/tcl interface is automatically generated by a software system called tcl_c++ developed by the author and described here. The objects keep track of different portions of the molecular machinery to allow different simulation techniques and boundary conditions to be applied as appropriate. This capability has been required to demonstrate (computationally) our gear's feasibility. A new distributed software architecture featuring a WWW universal client, CORBA distributed objects, and agent software is under consideration. The software architecture is intended to eventually enable a widely disbursed group to develop complex simulated molecular machines.

Monte Carlo Analysis of Molecule Absorption Probabilities in Diffusion-Based Nanoscale Communication Systems with Multiple Receivers.

PubMed

Arifler, Dogu; Arifler, Dizem

2017-04-01

For biomedical applications of nanonetworks, employing molecular communication for information transport is advantageous over nano-electromagnetic communication: molecular communication is potentially biocompatible and inherently energy-efficient. Recently, several studies have modeled receivers in diffusion-based molecular communication systems as "perfectly monitoring" or "perfectly absorbing" spheres based on idealized descriptions of chemoreception. In this paper, we focus on perfectly absorbing receivers and present methods to improve the accuracy of simulation procedures that are used to analyze these receivers. We employ schemes available from the chemical physics and biophysics literature and outline a Monte Carlo simulation algorithm that accounts for the possibility of molecule absorption during discrete time steps, leading to a more accurate analysis of absorption probabilities. Unlike most existing studies that consider a single receiver, this paper analyzes absorption probabilities for multiple receivers deterministically or randomly deployed in a region. For random deployments, the ultimate absorption probabilities as a function of transmitter-receiver distance are shown to fit well to power laws; the exponents derived become more negative as the number of receivers increases up to a limit beyond which no additional receivers can be "packed" in the deployment region. This paper is expected to impact the design of molecular nanonetworks with multiple absorbing receivers.

3D-QSAR, homology modeling, and molecular docking studies on spiropiperidines analogues as agonists of nociceptin/orphanin FQ receptor.

PubMed

Liu, Ming; He, Lin; Hu, Xiaopeng; Liu, Peiqing; Luo, Hai-Bin

2010-12-01

The nociceptin/orphanin FQ receptor (NOP) has been implicated in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have a great potential to be developed into anxiolytics. However, the crystal structure of NOP is still not available. In the present work, both structure-based and ligand-based modeling methods have been used to achieve a comprehensive understanding on 67N-substituted spiropiperidine analogues as NOP agonists. The comparative molecular-field analysis method was performed to formulate a reasonable 3D-QSAR model (cross-validated coefficient q(2)=0.819 and conventional r(2)=0.950), whose robustness and predictability were further verified by leave-eight-out, Y-randomization, and external test-set validations. The excellent performance of CoMFA to the affinity differences among these compounds was attributed to the contributions of electrostatic/hydrogen-bonding and steric/hydrophobic interactions, which was supported by the Surflex-Dock and CDOCKER molecular-docking simulations based on the 3D model of NOP built by the homology modeling method. The CoMFA contour maps and the molecular docking simulations were integrated to propose a binding mode for the spiropiperidine analogues at the binding site of NOP. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of mechanical load on the shuttling operation of molecular muscles

NASA Astrophysics Data System (ADS)

Lee, Seungjun; Lu, Wei

2009-06-01

We use molecular dynamics simulations to investigate the effect of mechanical force on stimulus-induced deformation of rotaxane-based artificial molecular muscles. The study shows that a small external force slows down the shuttling motion and leads to longer actuation time for a muscle to reach its full extension. Further increase in the force can significantly reduce the traveling distance of the ring, leading to reduced strain output. A force larger than 28 pN can completely suppress the shuttling motion, suggesting a limit of force output of molecular muscles.

Rapid communication: Computational simulation and analysis of a candidate for the design of a novel silk-based biopolymer.

PubMed

Golas, Ewa I; Czaplewski, Cezary

2014-09-01

This work theoretically investigates the mechanical properties of a novel silk-derived biopolymer as polymerized in silico from sericin and elastin-like monomers. Molecular Dynamics simulations and Steered Molecular Dynamics were the principal computational methods used, the latter of which applies an external force onto the system and thereby enables an observation of its response to stress. The models explored herein are single-molecule approximations, and primarily serve as tools in a rational design process for the preliminary assessment of properties in a new material candidate. © 2014 Wiley Periodicals, Inc.

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.

Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations.

PubMed

Liu, Kai; Watanabe, Etsurou; Kokubo, Hironori

2017-02-01

The binding mode prediction is of great importance to structure-based drug design. The discrimination of various binding poses of ligand generated by docking is a great challenge not only to docking score functions but also to the relatively expensive free energy calculation methods. Here we systematically analyzed the stability of various ligand poses under molecular dynamics (MD) simulation. First, a data set of 120 complexes was built based on the typical physicochemical properties of drug-like ligands. Three potential binding poses (one correct pose and two decoys) were selected for each ligand from self-docking in addition to the experimental pose. Then, five independent MD simulations for each pose were performed with different initial velocities for the statistical analysis. Finally, the stabilities of ligand poses under MD were evaluated and compared with the native one from crystal structure. We found that about 94% of the native poses were maintained stable during the simulations, which suggests that MD simulations are accurate enough to judge most experimental binding poses as stable properly. Interestingly, incorrect decoy poses were maintained much less and 38-44% of decoys could be excluded just by performing equilibrium MD simulations, though 56-62% of decoys were stable. The computationally-heavy binding free energy calculation can be performed only for these survived poses.

Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) Simulations of the Molecular Crystal alphaRDX

DTIC Science & Technology

2013-08-01

potential for HMX / RDX (3, 9). ...................................................................................8 1 1. Purpose This work...6 dispersion and electrostatic interactions. Constants for the SB potential are given in table 1. 8 Table 1. SB potential for HMX / RDX (3, 9...modeling dislocations in the energetic molecular crystal RDX using the Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) molecular

Large scale atomistic simulation of single-layer graphene growth on Ni(111) surface: molecular dynamics simulation based on a new generation of carbon-metal potential

NASA Astrophysics Data System (ADS)

Xu, Ziwei; Yan, Tianying; Liu, Guiwu; Qiao, Guanjun; Ding, Feng

2015-12-01

To explore the mechanism of graphene chemical vapor deposition (CVD) growth on a catalyst surface, a molecular dynamics (MD) simulation of carbon atom self-assembly on a Ni(111) surface based on a well-designed empirical reactive bond order potential was performed. We simulated single layer graphene with recorded size (up to 300 atoms per super-cell) and reasonably good quality by MD trajectories up to 15 ns. Detailed processes of graphene CVD growth, such as carbon atom dissolution and precipitation, formation of carbon chains of various lengths, polygons and small graphene domains were observed during the initial process of the MD simulation. The atomistic processes of typical defect healing, such as the transformation from a pentagon into a hexagon and from a pentagon-heptagon pair (5|7) to two adjacent hexagons (6|6), were revealed as well. The study also showed that higher temperature and longer annealing time are essential to form high quality graphene layers, which is in agreement with experimental reports and previous theoretical results.To explore the mechanism of graphene chemical vapor deposition (CVD) growth on a catalyst surface, a molecular dynamics (MD) simulation of carbon atom self-assembly on a Ni(111) surface based on a well-designed empirical reactive bond order potential was performed. We simulated single layer graphene with recorded size (up to 300 atoms per super-cell) and reasonably good quality by MD trajectories up to 15 ns. Detailed processes of graphene CVD growth, such as carbon atom dissolution and precipitation, formation of carbon chains of various lengths, polygons and small graphene domains were observed during the initial process of the MD simulation. The atomistic processes of typical defect healing, such as the transformation from a pentagon into a hexagon and from a pentagon-heptagon pair (5|7) to two adjacent hexagons (6|6), were revealed as well. The study also showed that higher temperature and longer annealing time are essential to form high quality graphene layers, which is in agreement with experimental reports and previous theoretical results. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06016h

Molecular dynamics study of oil adsorption on the rock surface in presence of silica nanoparticles

NASA Astrophysics Data System (ADS)

Salehzadeh, Jamal; Tohidi, Zahra; Jafari, Arezou

2018-01-01

Despite the increasing applications of nanoparticles in enhanced oil recovery (EOR), there is not enough information about the mechanisms and microscopic aspects of nanoparticles' effects. Therefore, in this research, molecular dynamics simulation is used to provide the molecular-scale insight for investigation of the silica nanoparticles effects on the oil adsorption on calcite surface for the first time. The surface interacts with the mixture of heptane and decane as the oil phase with mole ratio of 1/2 and silica nanoparticles are dispersed in distilled water with concentration of 7000 ppm. Based on the simulation results, by using nanoparticles surface adsorption behavior have been changed to hydrophilic and the oil molecules departed from the calcite. This result is based on the oil-calcite binding energy calculation which is decreased from 5224 kcal/mol to 3278 kcal/mol by using silica nanoparticles. In addition, calculation of radial distribution functions showed that after adding silica nanoparticles, the picks fall which means increasing in average distance between oil and calcite surface.

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

Molecular dynamics growth modeling of InAs1-xSbx-based type-II superlattice

NASA Astrophysics Data System (ADS)

Ciani, Anthony J.; Grein, Christoph H.; Irick, Barry; Miao, Maosheng; Kioussis, Nicholas

2017-09-01

Type-II strained-layer superlattices (T2SL) based on InAs1-xSbx are a promising photovoltaic detector material technology for thermal imaging; however, Shockley-Read-Hall recombination and generation rates are still too high for thermal imagers based on InAs1-xSbx T2SL to reach their ideal performance. Molecular dynamics simulations using the Stillinger-Weber (SW) empirical potentials are a useful tool to study the growth of tetrahedral coordinated crystals and the nonequilibrium formation of defects within them, including the long-range effects of strain. SW potentials for the possible atomic interactions among {Ga, In, As, Sb} were developed by fitting to ab initio calculations of elastically distorted zinc blende and diamond unit cells. The SW potentials were tested against experimental observations of molecular beam epitaxial (MBE) growth and then used to simulate the MBE growth of InAs/InAs0.5Sb0.5 T2SL on GaSb substrates over a range of processes parameters. The simulations showed and helped to explain Sb cross-incorporation into the InAs T2SL layers, Sb segregation within the InAsSb layers, and identified medium-range defect clusters involving interstitials and their induction of interstitial-vacancy pairs. Defect formation was also found to be affected by growth temperature and flux stoichiometry.

Structure-based design and evaluation of novel N-phenyl-1H-indol-2-amine derivatives for fat mass and obesity-associated (FTO) protein inhibition.

PubMed

Padariya, Monikaben; Kalathiya, Umesh

2016-10-01

Fat mass and obesity-associated (FTO) protein contributes to non-syndromic human obesity which refers to excessive fat accumulation in human body and results in health risk. FTO protein has become a promising target for anti-obesity medicines as there is an immense need for the rational design of potent inhibitors to treat obesity. In our study, a new scaffold N-phenyl-1H-indol-2-amine was selected as a base for FTO protein inhibitors by applying scaffold hopping approach. Using this novel scaffold, different derivatives were designed by extending scaffold structure with potential functional groups. Molecular docking simulations were carried out by using two different docking algorithm implemented in CDOCKER (flexible docking) and AutoDock programs (rigid docking). Analyzing results of rigid and flexible docking, compound MU06 was selected based on different properties and predicted binding affinities for further analysis. Molecular dynamics simulation of FTO/MU06 complex was performed to characterize structure rationale and binding stability. Certainly, Arg96 and His231 residue of FTO protein showed stable interaction with inhibitor MU06 throughout the production dynamics phase. Three residues of FTO protein (Arg96, Asp233, and His231) were found common in making H-bond interactions with MU06 during molecular dynamics simulation and CDOCKER docking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

PubMed Central

Wan, Minghui; Liao, Dongjiang; Peng, Guilin; Xu, Xin; Yin, Weiqiang; Guo, Guixin; Jiang, Funeng; Zhong, Weide

2017-01-01

Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition. PMID:29147652

The mechanism by which P250L mutation impairs flavivirus-NS1 dimerization: an investigation based on molecular dynamics simulations.

PubMed

Oliveira, Edson R A; de Alencastro, Ricardo B; Horta, Bruno A C

2016-09-01

The flavivirus non-structural protein 1 (NS1) is a conserved glycoprotein with as yet undefined biological function. This protein dimerizes when inside infected cells or associated to cell membranes but also forms lipid-associated hexamers when secreted to the extracellular space. A single amino acid substitution (P250L) is capable of preventing the dimerization of NS1 resulting in lower virulence and slower virus replication. In this work, based on molecular dynamics simulations of the dengue-2 virus NS1 [Formula: see text]-ladder monomer as a core model, we found that this mutation can induce several conformational changes that importantly affect critical monomer-monomer interactions. Based on additional simulations, we suggest a mechanism by which a highly orchestrated sequence of events propagate the local perturbations around the mutation site towards the dimer interface. The elucidation of such a mechanism could potentially support new strategies for rational production of live-attenuated vaccines and highlights a step forward in the development of novel anti-flavivirus measures.

Monte Carlo simulations on atropisomerism of thienotriazolodiazepines applicable to slow transition phenomena using potential energy surfaces by ab initio molecular orbital calculations.

PubMed

Morikami, Kenji; Itezono, Yoshiko; Nishimoto, Masahiro; Ohta, Masateru

2014-01-01

Compounds with a medium-sized flexible ring often show atropisomerism that is caused by the high-energy barriers between long-lived conformers that can be isolated and often have different biological properties to each other. In this study, the frequency of the transition between the two stable conformers, aS and aR, of thienotriazolodiazepine compounds with flexible 7-membered rings was estimated computationally by Monte Carlo (MC) simulations and validated experimentally by NMR experiments. To estimate the energy barriers for transitions as precisely as possible, the potential energy (PE) surfaces used in the MC simulations were calculated by molecular orbital (MO) methods. To accomplish the MC simulations with the MO-based PE surfaces in a practical central processing unit (CPU) time, the MO-based PE of each conformer was pre-calculated and stored before the MC simulations, and then only referred to during the MC simulations. The activation energies for transitions calculated by the MC simulations agreed well with the experimental ΔG determined by the NMR experiments. The analysis of the transition trajectories of the MC simulations revealed that the transition occurred not only through the transition states, but also through many different transition paths. Our computational methods gave us quantitative estimates of atropisomerism of the thienotriazolodiazepine compounds in a practical period of time, and the method could be applicable for other slow-dynamics phenomena that cannot be investigated by other atomistic simulations.

Equilibration and analysis of first-principles molecular dynamics simulations of water

NASA Astrophysics Data System (ADS)

Dawson, William; Gygi, François

2018-03-01

First-principles molecular dynamics (FPMD) simulations based on density functional theory are becoming increasingly popular for the description of liquids. In view of the high computational cost of these simulations, the choice of an appropriate equilibration protocol is critical. We assess two methods of estimation of equilibration times using a large dataset of first-principles molecular dynamics simulations of water. The Gelman-Rubin potential scale reduction factor [A. Gelman and D. B. Rubin, Stat. Sci. 7, 457 (1992)] and the marginal standard error rule heuristic proposed by White [Simulation 69, 323 (1997)] are evaluated on a set of 32 independent 64-molecule simulations of 58 ps each, amounting to a combined cumulative time of 1.85 ns. The availability of multiple independent simulations also allows for an estimation of the variance of averaged quantities, both within MD runs and between runs. We analyze atomic trajectories, focusing on correlations of the Kohn-Sham energy, pair correlation functions, number of hydrogen bonds, and diffusion coefficient. The observed variability across samples provides a measure of the uncertainty associated with these quantities, thus facilitating meaningful comparisons of different approximations used in the simulations. We find that the computed diffusion coefficient and average number of hydrogen bonds are affected by a significant uncertainty in spite of the large size of the dataset used. A comparison with classical simulations using the TIP4P/2005 model confirms that the variability of the diffusivity is also observed after long equilibration times. Complete atomic trajectories and simulation output files are available online for further analysis.

Equilibration and analysis of first-principles molecular dynamics simulations of water.

PubMed

Dawson, William; Gygi, François

2018-03-28

First-principles molecular dynamics (FPMD) simulations based on density functional theory are becoming increasingly popular for the description of liquids. In view of the high computational cost of these simulations, the choice of an appropriate equilibration protocol is critical. We assess two methods of estimation of equilibration times using a large dataset of first-principles molecular dynamics simulations of water. The Gelman-Rubin potential scale reduction factor [A. Gelman and D. B. Rubin, Stat. Sci. 7, 457 (1992)] and the marginal standard error rule heuristic proposed by White [Simulation 69, 323 (1997)] are evaluated on a set of 32 independent 64-molecule simulations of 58 ps each, amounting to a combined cumulative time of 1.85 ns. The availability of multiple independent simulations also allows for an estimation of the variance of averaged quantities, both within MD runs and between runs. We analyze atomic trajectories, focusing on correlations of the Kohn-Sham energy, pair correlation functions, number of hydrogen bonds, and diffusion coefficient. The observed variability across samples provides a measure of the uncertainty associated with these quantities, thus facilitating meaningful comparisons of different approximations used in the simulations. We find that the computed diffusion coefficient and average number of hydrogen bonds are affected by a significant uncertainty in spite of the large size of the dataset used. A comparison with classical simulations using the TIP4P/2005 model confirms that the variability of the diffusivity is also observed after long equilibration times. Complete atomic trajectories and simulation output files are available online for further analysis.

All-atom Simulation of Amyloid Aggregates

NASA Astrophysics Data System (ADS)

Berhanu, Workalemahu M.; Alred, Erik J.; Bernhardt, Nathan A.; Hansmann, Ulrich H. E.

Molecular simulations are now commonly used to complement experiments in the investigation of amyloid formation and their role in human diseases. While various simulations based on enhanced sampling techniques are used in amyloid formation simulations, this article will focus on those using standard atomistic simulations to evaluate the stability of fibril models. Such studies explore the limitations that arise from the choice of force field or polymorphism; and explore the stability of in vivo and in vitro forms of Aβ fibril aggregates, and the role of heterologous seeding as a link between different amyloid diseases.

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.

Efficient Conformational Sampling in Explicit Solvent Using a Hybrid Replica Exchange Molecular Dynamics Method

DTIC Science & Technology

2011-12-01

REMD while reproducing the energy landscape of explicit solvent simulations . ’ INTRODUCTION Molecular dynamics (MD) simulations of proteins can pro...Mongan, J.; McCammon, J. A. Accelerated molecular dynamics : a promising and efficient simulation method for biomolecules. J. Chem. Phys. 2004, 120 (24...Chemical Theory and Computation ARTICLE (8) Abraham,M. J.; Gready, J. E. Ensuringmixing efficiency of replica- exchange molecular dynamics simulations . J

Multiscale Quantum Mechanics/Molecular Mechanics Simulations with Neural Networks.

PubMed

Shen, Lin; Wu, Jingheng; Yang, Weitao

2016-10-11

Molecular dynamics simulation with multiscale quantum mechanics/molecular mechanics (QM/MM) methods is a very powerful tool for understanding the mechanism of chemical and biological processes in solution or enzymes. However, its computational cost can be too high for many biochemical systems because of the large number of ab initio QM calculations. Semiempirical QM/MM simulations have much higher efficiency. Its accuracy can be improved with a correction to reach the ab initio QM/MM level. The computational cost on the ab initio calculation for the correction determines the efficiency. In this paper we developed a neural network method for QM/MM calculation as an extension of the neural-network representation reported by Behler and Parrinello. With this approach, the potential energy of any configuration along the reaction path for a given QM/MM system can be predicted at the ab initio QM/MM level based on the semiempirical QM/MM simulations. We further applied this method to three reactions in water to calculate the free energy changes. The free-energy profile obtained from the semiempirical QM/MM simulation is corrected to the ab initio QM/MM level with the potential energies predicted with the constructed neural network. The results are in excellent accordance with the reference data that are obtained from the ab initio QM/MM molecular dynamics simulation or corrected with direct ab initio QM/MM potential energies. Compared with the correction using direct ab initio QM/MM potential energies, our method shows a speed-up of 1 or 2 orders of magnitude. It demonstrates that the neural network method combined with the semiempirical QM/MM calculation can be an efficient and reliable strategy for chemical reaction simulations.

Prediction of Ordered Water Molecules in Protein Binding Sites from Molecular Dynamics Simulations: The Impact of Ligand Binding on Hydration Networks.

PubMed

Rudling, Axel; Orro, Adolfo; Carlsson, Jens

2018-02-26

Water plays a major role in ligand binding and is attracting increasing attention in structure-based drug design. Water molecules can make large contributions to binding affinity by bridging protein-ligand interactions or by being displaced upon complex formation, but these phenomena are challenging to model at the molecular level. Herein, networks of ordered water molecules in protein binding sites were analyzed by clustering of molecular dynamics (MD) simulation trajectories. Locations of ordered waters (hydration sites) were first identified from simulations of high resolution crystal structures of 13 protein-ligand complexes. The MD-derived hydration sites reproduced 73% of the binding site water molecules observed in the crystal structures. If the simulations were repeated without the cocrystallized ligands, a majority (58%) of the crystal waters in the binding sites were still predicted. In addition, comparison of the hydration sites obtained from simulations carried out in the absence of ligands to those identified for the complexes revealed that the networks of ordered water molecules were preserved to a large extent, suggesting that the locations of waters in a protein-ligand interface are mainly dictated by the protein. Analysis of >1000 crystal structures showed that hydration sites bridged protein-ligand interactions in complexes with different ligands, and those with high MD-derived occupancies were more likely to correspond to experimentally observed ordered water molecules. The results demonstrate that ordered water molecules relevant for modeling of protein-ligand complexes can be identified from MD simulations. Our findings could contribute to development of improved methods for structure-based virtual screening and lead optimization.

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

NASA Astrophysics Data System (ADS)

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

2002-06-01

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

Two-bead polarizable water models combined with a two-bead multipole force field (TMFF) for coarse-grained simulation of proteins.

PubMed

Li, Min; Zhang, John Z H

2017-03-08

The development of polarizable water models at coarse-grained (CG) levels is of much importance to CG molecular dynamics simulations of large biomolecular systems. In this work, we combined the newly developed two-bead multipole force field (TMFF) for proteins with the two-bead polarizable water models to carry out CG molecular dynamics simulations for benchmark proteins. In our simulations, two different two-bead polarizable water models are employed, the RTPW model representing five water molecules by Riniker et al. and the LTPW model representing four water molecules. The LTPW model is developed in this study based on the Martini three-bead polarizable water model. Our simulation results showed that the combination of TMFF with the LTPW model significantly stabilizes the protein's native structure in CG simulations, while the use of the RTPW model gives better agreement with all-atom simulations in predicting the residue-level fluctuation dynamics. Overall, the TMFF coupled with the two-bead polarizable water models enables one to perform an efficient and reliable CG dynamics study of the structural and functional properties of large biomolecules.

Molecular effective coverage surface area of optical clearing agents for predicting optical clearing potential

NASA Astrophysics Data System (ADS)

Feng, Wei; Ma, Ning; Zhu, Dan

2015-03-01

The improvement of methods for optical clearing agent prediction exerts an important impact on tissue optical clearing technique. The molecular dynamic simulation is one of the most convincing and simplest approaches to predict the optical clearing potential of agents by analyzing the hydrogen bonds, hydrogen bridges and hydrogen bridges type forming between agents and collagen. However, the above analysis methods still suffer from some problem such as analysis of cyclic molecule by reason of molecular conformation. In this study, a molecular effective coverage surface area based on the molecular dynamic simulation was proposed to predict the potential of optical clearing agents. Several typical cyclic molecules, fructose, glucose and chain molecules, sorbitol, xylitol were analyzed by calculating their molecular effective coverage surface area, hydrogen bonds, hydrogen bridges and hydrogen bridges type, respectively. In order to verify this analysis methods, in vitro skin samples optical clearing efficacy were measured after 25 min immersing in the solutions, fructose, glucose, sorbitol and xylitol at concentration of 3.5 M using 1951 USAF resolution test target. The experimental results show accordance with prediction of molecular effective coverage surface area. Further to compare molecular effective coverage surface area with other parameters, it can show that molecular effective coverage surface area has a better performance in predicting OCP of agents.

Mixed quantum-classical simulations of the vibrational relaxation of photolyzed carbon monoxide in a hemoprotein

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

Schubert, Alexander, E-mail: schubert@irsamc.ups-tlse.fr; Meier, Christoph; Falvo, Cyril

2016-08-07

We present mixed quantum-classical simulations on relaxation and dephasing of vibrationally excited carbon monoxide within a protein environment. The methodology is based on a vibrational surface hopping approach treating the vibrational states of CO quantum mechanically, while all remaining degrees of freedom are described by means of classical molecular dynamics. The CO vibrational states form the “surfaces” for the classical trajectories of protein and solvent atoms. In return, environmentally induced non-adiabatic couplings between these states cause transitions describing the vibrational relaxation from first principles. The molecular dynamics simulation yields a detailed atomistic picture of the energy relaxation pathways, taking themore » molecular structure and dynamics of the protein and its solvent fully into account. Using the ultrafast photolysis of CO in the hemoprotein FixL as an example, we study the relaxation of vibrationally excited CO and evaluate the role of each of the FixL residues forming the heme pocket.« less

Thermodynamic Modeling of Ag-Ni System Combining Experiments and Molecular Dynamic Simulation

NASA Astrophysics Data System (ADS)

Rajkumar, V. B.; Chen, Sinn-wen

2017-04-01

Ag-Ni is a simple and important system with immiscible liquids and (Ag,Ni) phases. Previously, this system has been thermodynamically modeled utilizing certain thermochemical and phase equilibria information based on conjecture. An attempt is made in this study to determine the missing information which are difficult to measure experimentally. The boundaries of the liquid miscibility gap at high temperatures are determined using a pyrometer. The temperature of the liquid ⇌ (Ag) + (Ni) eutectic reaction is measured using differential thermal analysis. Tie-lines of the Ag-Ni system at 1023 K and 1473 K are measured using a conventional metallurgical method. The enthalpy of mixing of the liquid at 1773 K and the (Ag,Ni) at 973 K is calculated by molecular dynamics simulation using a large-scale atomic/molecular massively parallel simulator. These results along with literature information are used to model the Gibbs energy of the liquid and (Ag,Ni) by a calculation of phase diagrams approach, and the Ag-Ni phase diagram is then calculated.

Molecular dynamics simulations of lysozyme-lipid systems: probing the early steps of protein aggregation.

PubMed

Trusova, Valeriya M; Gorbenko, Galyna P

2017-07-10

Using the molecular dynamics simulation, the role of lipids in the lysozyme transition into the aggregation-competent conformation has been clarified. Analysis of the changes of lysozyme secondary structure upon its interactions with the model bilayer membranes composed of phosphatidylcholine and its mixtures with phosphatidylglycerol (10, 40, and 80 mol%) within the time interval of 100 ns showed that lipid-bound protein is characterized by the increased content of β-structures. Along with this, the formation of protein-lipid complexes was accompanied by the increase in the gyration radius and the decrease in RMSD of polypeptide chain. The results obtained were interpreted in terms of the partial unfolding of lysozyme molecule on the lipid matrix, with the magnitude of this effect being increased with increasing the fraction of anionic lipids. Based on the results of molecular dynamics simulation, a hypothetical model of the nucleation of lysozyme amyloid fibrils in a membrane environment was suggested.

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles.

PubMed

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F; Perez, Danny

2017-10-21

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles

NASA Astrophysics Data System (ADS)

Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F.; Perez, Danny

2017-10-01

Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

Deviation from equilibrium conditions in molecular dynamic simulations of homogeneous nucleation.

PubMed

Halonen, Roope; Zapadinsky, Evgeni; Vehkamäki, Hanna

2018-04-28

We present a comparison between Monte Carlo (MC) results for homogeneous vapour-liquid nucleation of Lennard-Jones clusters and previously published values from molecular dynamics (MD) simulations. Both the MC and MD methods sample real cluster configuration distributions. In the MD simulations, the extent of the temperature fluctuation is usually controlled with an artificial thermostat rather than with more realistic carrier gas. In this study, not only a primarily velocity scaling thermostat is considered, but also Nosé-Hoover, Berendsen, and stochastic Langevin thermostat methods are covered. The nucleation rates based on a kinetic scheme and the canonical MC calculation serve as a point of reference since they by definition describe an equilibrated system. The studied temperature range is from T = 0.3 to 0.65 ϵ/k. The kinetic scheme reproduces well the isothermal nucleation rates obtained by Wedekind et al. [J. Chem. Phys. 127, 064501 (2007)] using MD simulations with carrier gas. The nucleation rates obtained by artificially thermostatted MD simulations are consistently lower than the reference nucleation rates based on MC calculations. The discrepancy increases up to several orders of magnitude when the density of the nucleating vapour decreases. At low temperatures, the difference to the MC-based reference nucleation rates in some cases exceeds the maximal nonisothermal effect predicted by classical theory of Feder et al. [Adv. Phys. 15, 111 (1966)].

Deviation from equilibrium conditions in molecular dynamic simulations of homogeneous nucleation

NASA Astrophysics Data System (ADS)

Halonen, Roope; Zapadinsky, Evgeni; Vehkamäki, Hanna

2018-04-01

We present a comparison between Monte Carlo (MC) results for homogeneous vapour-liquid nucleation of Lennard-Jones clusters and previously published values from molecular dynamics (MD) simulations. Both the MC and MD methods sample real cluster configuration distributions. In the MD simulations, the extent of the temperature fluctuation is usually controlled with an artificial thermostat rather than with more realistic carrier gas. In this study, not only a primarily velocity scaling thermostat is considered, but also Nosé-Hoover, Berendsen, and stochastic Langevin thermostat methods are covered. The nucleation rates based on a kinetic scheme and the canonical MC calculation serve as a point of reference since they by definition describe an equilibrated system. The studied temperature range is from T = 0.3 to 0.65 ɛ/k. The kinetic scheme reproduces well the isothermal nucleation rates obtained by Wedekind et al. [J. Chem. Phys. 127, 064501 (2007)] using MD simulations with carrier gas. The nucleation rates obtained by artificially thermostatted MD simulations are consistently lower than the reference nucleation rates based on MC calculations. The discrepancy increases up to several orders of magnitude when the density of the nucleating vapour decreases. At low temperatures, the difference to the MC-based reference nucleation rates in some cases exceeds the maximal nonisothermal effect predicted by classical theory of Feder et al. [Adv. Phys. 15, 111 (1966)].

Hard Sphere Simulation by Event-Driven Molecular Dynamics: Breakthrough, Numerical Difficulty, and Overcoming the issues

NASA Astrophysics Data System (ADS)

Isobe, Masaharu

Hard sphere/disk systems are among the simplest models and have been used to address numerous fundamental problems in the field of statistical physics. The pioneering numerical works on the solid-fluid phase transition based on Monte Carlo (MC) and molecular dynamics (MD) methods published in 1957 represent historical milestones, which have had a significant influence on the development of computer algorithms and novel tools to obtain physical insights. This chapter addresses the works of Alder's breakthrough regarding hard sphere/disk simulation: (i) event-driven molecular dynamics, (ii) long-time tail, (iii) molasses tail, and (iv) two-dimensional melting/crystallization. From a numerical viewpoint, there are serious issues that must be overcome for further breakthrough. Here, we present a brief review of recent progress in this area.

Molecular beam mass spectrometer development

NASA Technical Reports Server (NTRS)

Brock, F. J.; Hueser, J. E.

1976-01-01

An analytical model, based on the kinetics theory of a drifting Maxwellian gas is used to determine the nonequilibrium molecular density distribution within a hemispherical shell open aft with its axis parallel to its velocity. The concept of a molecular shield in terrestrial orbit above 200 km is also analyzed using the kinetic theory of a drifting Maxwellian gas. Data are presented for the components of the gas density within the shield due to the free stream atmosphere, outgassing from the shield and enclosed experiments, and atmospheric gas scattered off a shield orbiter system. A description is given of a FORTRAN program for computating the three dimensional transition flow regime past the space shuttle orbiter that employs the Monte Carlo simulation method to model real flow by some thousands of simulated molecules.

Electron-phonon interaction within classical molecular dynamics

DOE PAGES

Tamm, A.; Samolyuk, G.; Correa, A. A.; ...

2016-07-14

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

Directly calculated electrical conductivity of hot dense hydrogen from molecular dynamics simulation beyond Kubo-Greenwood formula

NASA Astrophysics Data System (ADS)

Ma, Qian; Kang, Dongdong; Zhao, Zengxiu; Dai, Jiayu

2018-01-01

Electrical conductivity of hot dense hydrogen is directly calculated by molecular dynamics simulation with a reduced electron force field method, in which the electrons are represented as Gaussian wave packets with fixed sizes. Here, the temperature is higher than electron Fermi temperature ( T > 300 eV , ρ = 40 g / cc ). The present method can avoid the Coulomb catastrophe and give the limit of electrical conductivity based on the Coulomb interaction. We investigate the effect of ion-electron coupled movements, which is lost in the static method such as density functional theory based Kubo-Greenwood framework. It is found that the ionic dynamics, which contributes to the dynamical electrical microfield and electron-ion collisions, will reduce the conductivity significantly compared with the fixed ion configuration calculations.

Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

NASA Astrophysics Data System (ADS)

Sato, Yukari; Natsume, Ryo; Prokop, Zbynek; Brezovsky, Jan; Chaloupkova, Radka; Damborsky, Jiri; Nagata, Yuji; Senda, Toshiya

Enzymes are widely used for the synthesis of pharmaceuticals, agrochemicals, and food additives because they can catalyze high enantioselective transformations. In order to construct selective enzymes by protein engineering, it is important to understand the molecular basis of enzyme-substrate interactions that contribute to enantioselectivity. The haloalkane dehalogenase DbjA showed high enantioselectivity for two racemic mixtures: α-bromoesters and β-bromoalkanes. Thermodynamic analysis, protein crystallography, and computer simulations indicated that DbjA carries two bases for the enantiodiscrimination of each racemic mixture. This study helps us understand the molecular basis of the enantioselectivity and opens up new possibilities for constructing enantiospecific biocatalysts through protein engineering.

Insight of Transmembrane Processes of Self-Assembling Nanotubes Based on a Cyclic Peptide Using Coarse Grained Molecular Dynamics Simulation.

PubMed

Fu, Yankai; Yan, Tingxuan; Xu, Xia

2017-09-28

Transmembrane self-assembling cyclic peptide (SCP) nanotubes are promising candidates for delivering specific molecules through cell membranes. The detailed mechanisms behind the transmembrane processes, as well as stabilization factors of transmembrane structures, are difficult to elucidate through experiments. In this study, the effects of peptide sequence and oligomeric state on the transmembrane capabilities of SCP nanotubes and the perturbation of embedded SCP nanotubes acting on the membrane were investigated based on coarse grained molecular dynamics simulation. The simulation results reveal that hydrophilic SCP oligomers result in the elevation of the energy barrier while the oligomerization of hydrophobic SCPs causes the reduction of the energy barrier, further leading to membrane insertion. Once SCP nanotubes are embedded, membrane properties such as density, thickness, ordering state and lateral mobility are adjusted along the radial direction. This study provides insight into the transmembrane strategy of SCP nanotubes and sheds light on designing novel transport systems.

Employing multi-GPU power for molecular dynamics simulation: an extension of GALAMOST

NASA Astrophysics Data System (ADS)

Zhu, You-Liang; Pan, Deng; Li, Zhan-Wei; Liu, Hong; Qian, Hu-Jun; Zhao, Yang; Lu, Zhong-Yuan; Sun, Zhao-Yan

2018-04-01

We describe the algorithm of employing multi-GPU power on the basis of Message Passing Interface (MPI) domain decomposition in a molecular dynamics code, GALAMOST, which is designed for the coarse-grained simulation of soft matters. The code of multi-GPU version is developed based on our previous single-GPU version. In multi-GPU runs, one GPU takes charge of one domain and runs single-GPU code path. The communication between neighbouring domains takes a similar algorithm of CPU-based code of LAMMPS, but is optimised specifically for GPUs. We employ a memory-saving design which can enlarge maximum system size at the same device condition. An optimisation algorithm is employed to prolong the update period of neighbour list. We demonstrate good performance of multi-GPU runs on the simulation of Lennard-Jones liquid, dissipative particle dynamics liquid, polymer and nanoparticle composite, and two-patch particles on workstation. A good scaling of many nodes on cluster for two-patch particles is presented.

Challenges in molecular simulation of homogeneous ice nucleation

NASA Astrophysics Data System (ADS)

Brukhno, Andrey V.; Anwar, Jamshed; Davidchack, Ruslan; Handel, Richard

2008-12-01

We address the problem of recognition and growth of ice nuclei in simulation of supercooled bulk water. Bond orientation order parameters based on the spherical harmonics analysis are shown to be ineffective when applied to ice nucleation. Here we present an alternative method which robustly differentiates between hexagonal and cubic ice forms. The method is based on accumulation of the maximum projection of bond orientations onto a set of predetermined vectors, where different terms can contribute with opposite signs with the result that the irrelevant or incompatible molecular arrangements are damped out. We also introduce an effective cluster size by assigning a quality weight to each molecule in an ice-like cluster. We employ our cluster analysis in Monte Carlo simulation of homogeneous ice formation. Replica-exchange umbrella sampling is used for biasing the growth of the largest cluster and calculating the associated free energy barrier. Our results suggest that the ice formation can be seen as a two-stage process. Initially, short tetrahedrally arranged threads and rings are present; these become correlated and form a diffuse ice-genic network. Later, hydrogen bond arrangements within the amorphous ice-like structure gradually settle down and simultaneously 'tune-up' nearby water molecules. As a result, a well-shaped ice core emerges and spreads throughout the system. The process is very slow and diverse owing to the rough energetic landscape and sluggish molecular motion in supercooled water, while large configurational fluctuations are needed for crystallization to occur. In the small systems studied so far the highly cooperative molecular rearrangements eventually lead to a relatively fast percolation of the forming ice structure through the periodic boundaries, which inevitably affects the simulation results.

Search for β2 Adrenergic Receptor Ligands by Virtual Screening via Grid Computing and Investigation of Binding Modes by Docking and Molecular Dynamics Simulations

PubMed Central

Bai, Qifeng; Shao, Yonghua; Pan, Dabo; Zhang, Yang; Liu, Huanxiang; Yao, Xiaojun

2014-01-01

We designed a program called MolGridCal that can be used to screen small molecule database in grid computing on basis of JPPF grid environment. Based on MolGridCal program, we proposed an integrated strategy for virtual screening and binding mode investigation by combining molecular docking, molecular dynamics (MD) simulations and free energy calculations. To test the effectiveness of MolGridCal, we screened potential ligands for β2 adrenergic receptor (β2AR) from a database containing 50,000 small molecules. MolGridCal can not only send tasks to the grid server automatically, but also can distribute tasks using the screensaver function. As for the results of virtual screening, the known agonist BI-167107 of β2AR is ranked among the top 2% of the screened candidates, indicating MolGridCal program can give reasonable results. To further study the binding mode and refine the results of MolGridCal, more accurate docking and scoring methods are used to estimate the binding affinity for the top three molecules (agonist BI-167107, neutral antagonist alprenolol and inverse agonist ICI 118,551). The results indicate agonist BI-167107 has the best binding affinity. MD simulation and free energy calculation are employed to investigate the dynamic interaction mechanism between the ligands and β2AR. The results show that the agonist BI-167107 also has the lowest binding free energy. This study can provide a new way to perform virtual screening effectively through integrating molecular docking based on grid computing, MD simulations and free energy calculations. The source codes of MolGridCal are freely available at http://molgridcal.codeplex.com. PMID:25229694

Uncertainty Quantification in Alchemical Free Energy Methods.

PubMed

Bhati, Agastya P; Wan, Shunzhou; Hu, Yuan; Sherborne, Brad; Coveney, Peter V

2018-06-12

Alchemical free energy methods have gained much importance recently from several reports of improved ligand-protein binding affinity predictions based on their implementation using molecular dynamics simulations. A large number of variants of such methods implementing different accelerated sampling techniques and free energy estimators are available, each claimed to be better than the others in its own way. However, the key features of reproducibility and quantification of associated uncertainties in such methods have barely been discussed. Here, we apply a systematic protocol for uncertainty quantification to a number of popular alchemical free energy methods, covering both absolute and relative free energy predictions. We show that a reliable measure of error estimation is provided by ensemble simulation-an ensemble of independent MD simulations-which applies irrespective of the free energy method. The need to use ensemble methods is fundamental and holds regardless of the duration of time of the molecular dynamics simulations performed.

Glass Formation of n-Butanol: Coarse-grained Molecular Dynamics Simulations Using Gay-Berne Potential Model

NASA Astrophysics Data System (ADS)

Xie, Gui-long; Zhang, Yong-hong; Huang, Shi-ping

2012-04-01

Using coarse-grained molecular dynamics simulations based on Gay-Berne potential model, we have simulated the cooling process of liquid n-butanol. A new set of GB parameters are obtained by fitting the results of density functional theory calculations. The simulations are carried out in the range of 290-50 K with temperature decrements of 10 K. The cooling characteristics are determined on the basis of the variations of the density, the potential energy and orientational order parameter with temperature, whose slopes all show discontinuity. Both the radial distribution function curves and the second-rank orientational correlation function curves exhibit splitting in the second peak. Using the discontinuous change of these thermodynamic and structure properties, we obtain the glass transition at an estimate of temperature Tg=120±10 K, which is in good agreement with experimental results 110±1 K.

High temperature phonon dispersion in graphene using classical molecular dynamics

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

Anees, P., E-mail: anees@igcar.gov.in; Panigrahi, B. K.; Valsakumar, M. C., E-mail: anees@igcar.gov.in

2014-04-24

Phonon dispersion and phonon density of states of graphene are calculated using classical molecular dynamics simulations. In this method, the dynamical matrix is constructed based on linear response theory by computing the displacement of atoms during the simulations. The computed phonon dispersions show excellent agreement with experiments. The simulations are done in both NVT and NPT ensembles at 300 K and found that the LO/TO modes are getting hardened at the Γ point. The NPT ensemble simulations capture the anharmonicity of the crystal accurately and the hardening of LO/TO modes is more pronounced. We also found that at 300 Kmore » the C-C bond length reduces below the equilibrium value and the ZA bending mode frequency becomes imaginary close to Γ along K-Γ direction, which indicates instability of the flat 2D graphene sheets.« less

Alterations in gut transport of minerals and in binding proteins during simulated weightlessness

NASA Technical Reports Server (NTRS)

Bikle, D. D.

1984-01-01

The structural components of the skeleton develop and are maintained in a 1 g environment, shaped by the mechanical load to which they are constantly exposed. Altering such a mechanical load by reducing the gravitational force imposed on the system, as in space flight, has profound effects on the skeleton and permits an exploration of the molecular events which regulate normal skeletal homeostasis. The objective was to determine whether simulated weightlessness reduced intestinal calcium transport, and if so, to determine the molecular mechanisms for such an effect. A nonstressful tail suspension in which the rats gained weight normally while suspended was used to simulate weightlessness. A significant change in intestinal calcium transport was not demonstrated. However, a cyclic change in bone formation with suspension was shown. Based on these observations, the objective changed to determination of the hormonal regulation of bone formation during simulated weightlessness.

Lightweight Object Oriented Structure analysis: Tools for building Tools to Analyze Molecular Dynamics Simulations

PubMed Central

Romo, Tod D.; Leioatts, Nicholas; Grossfield, Alan

2014-01-01

LOOS (Lightweight Object-Oriented Structure-analysis) is a C++ library designed to facilitate making novel tools for analyzing molecular dynamics simulations by abstracting out the repetitive tasks, allowing developers to focus on the scientifically relevant part of the problem. LOOS supports input using the native file formats of most common biomolecular simulation packages, including CHARMM, NAMD, Amber, Tinker, and Gromacs. A dynamic atom selection language based on the C expression syntax is included and is easily accessible to the tool-writer. In addition, LOOS is bundled with over 120 pre-built tools, including suites of tools for analyzing simulation convergence, 3D histograms, and elastic network models. Through modern C++ design, LOOS is both simple to develop with (requiring knowledge of only 4 core classes and a few utility functions) and is easily extensible. A python interface to the core classes is also provided, further facilitating tool development. PMID:25327784

Comparison of volume and surface area nonpolar solvation free energy terms for implicit solvent simulations.

PubMed

Lee, Michael S; Olson, Mark A

2013-07-28

Implicit solvent models for molecular dynamics simulations are often composed of polar and nonpolar terms. Typically, the nonpolar solvation free energy is approximated by the solvent-accessible-surface area times a constant factor. More sophisticated approaches incorporate an estimate of the attractive dispersion forces of the solvent and∕or a solvent-accessible volume cavitation term. In this work, we confirm that a single volume-based nonpolar term most closely fits the dispersion and cavitation forces obtained from benchmark explicit solvent simulations of fixed protein conformations. Next, we incorporated the volume term into molecular dynamics simulations and find the term is not universally suitable for folding up small proteins. We surmise that while mean-field cavitation terms such as volume and SASA often tilt the energy landscape towards native-like folds, they also may sporadically introduce bottlenecks into the folding pathway that hinder the progression towards the native state.

Lightweight object oriented structure analysis: tools for building tools to analyze molecular dynamics simulations.

PubMed

Romo, Tod D; Leioatts, Nicholas; Grossfield, Alan

2014-12-15

LOOS (Lightweight Object Oriented Structure-analysis) is a C++ library designed to facilitate making novel tools for analyzing molecular dynamics simulations by abstracting out the repetitive tasks, allowing developers to focus on the scientifically relevant part of the problem. LOOS supports input using the native file formats of most common biomolecular simulation packages, including CHARMM, NAMD, Amber, Tinker, and Gromacs. A dynamic atom selection language based on the C expression syntax is included and is easily accessible to the tool-writer. In addition, LOOS is bundled with over 140 prebuilt tools, including suites of tools for analyzing simulation convergence, three-dimensional histograms, and elastic network models. Through modern C++ design, LOOS is both simple to develop with (requiring knowledge of only four core classes and a few utility functions) and is easily extensible. A python interface to the core classes is also provided, further facilitating tool development. © 2014 Wiley Periodicals, Inc.

Comparison of volume and surface area nonpolar solvation free energy terms for implicit solvent simulations

NASA Astrophysics Data System (ADS)

Lee, Michael S.; Olson, Mark A.

2013-07-01

Implicit solvent models for molecular dynamics simulations are often composed of polar and nonpolar terms. Typically, the nonpolar solvation free energy is approximated by the solvent-accessible-surface area times a constant factor. More sophisticated approaches incorporate an estimate of the attractive dispersion forces of the solvent and/or a solvent-accessible volume cavitation term. In this work, we confirm that a single volume-based nonpolar term most closely fits the dispersion and cavitation forces obtained from benchmark explicit solvent simulations of fixed protein conformations. Next, we incorporated the volume term into molecular dynamics simulations and find the term is not universally suitable for folding up small proteins. We surmise that while mean-field cavitation terms such as volume and SASA often tilt the energy landscape towards native-like folds, they also may sporadically introduce bottlenecks into the folding pathway that hinder the progression towards the native state.

Principal component analysis of binding energies for single-point mutants of hT2R16 bound to an agonist correlate with experimental mutant cell response.

PubMed

Chen, Derek E; Willick, Darryl L; Ruckel, Joseph B; Floriano, Wely B

2015-01-01

Directed evolution is a technique that enables the identification of mutants of a particular protein that carry a desired property by successive rounds of random mutagenesis, screening, and selection. This technique has many applications, including the development of G protein-coupled receptor-based biosensors and designer drugs for personalized medicine. Although effective, directed evolution is not without challenges and can greatly benefit from the development of computational techniques to predict the functional outcome of single-point amino acid substitutions. In this article, we describe a molecular dynamics-based approach to predict the effects of single amino acid substitutions on agonist binding (salicin) to a human bitter taste receptor (hT2R16). An experimentally determined functional map of single-point amino acid substitutions was used to validate the whole-protein molecular dynamics-based predictive functions. Molecular docking was used to construct a wild-type agonist-receptor complex, providing a starting structure for single-point substitution simulations. The effects of each single amino acid substitution in the functional response of the receptor to its agonist were estimated using three binding energy schemes with increasing inclusion of solvation effects. We show that molecular docking combined with molecular mechanics simulations of single-point mutants of the agonist-receptor complex accurately predicts the functional outcome of single amino acid substitutions in a human bitter taste receptor.

Identification of 1H-indene-(1,3,5,6)-tetrol derivatives as potent pancreatic lipase inhibitors using molecular docking and molecular dynamics approach.

PubMed

Kalathiya, Umesh; Padariya, M; Baginski, M

2016-11-01

Pancreatic lipase is a potential therapeutic target to treat diet-induced obesity in humans, as obesity-related diseases continue to be a global problem. Despite intensive research on finding potential inhibitors, very few compounds have been introduced to clinical studies. In this work, new chemical scaffold 1H-indene-(1,3,5,6)-tetrol was proposed using knowledge-based approach, and 36 inhibitors were derived by modifying its functional groups at different positions in scaffold. To explore binding affinity and interactions of ligands with protein, CDOCKER and AutoDock programs were used for molecular docking studies. Analyzing results of rigid and flexible docking algorithms, inhibitors C_12, C_24, and C_36 were selected based on different properties and high predicted binding affinities for further analysis. These three inhibitors have different moieties placed at different functional groups in scaffold, and to characterize structural rationales for inhibitory activities of compounds, molecular dynamics simulations were performed (500 nSec). It has been shown through simulations that two structural fragments (indene and indole) in inhibitor can be treated as isosteric structures and their position at binding cleft can be replaced by each other. Taking into account these information, two lines of inhibitors can further be developed, each line based on a different core scaffold, that is, indene/indole. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

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

Bertholon, François; Harant, Olivier; Bourlon, Bertrand

This article introduces a joined Bayesian estimation of gas samples issued from a gas chromatography column (GC) coupled with a NEMS sensor based on Giddings Eyring microscopic molecular stochastic model. The posterior distribution is sampled using a Monte Carlo Markov Chain and Gibbs sampling. Parameters are estimated using the posterior mean. This estimation scheme is finally applied on simulated and real datasets using this molecular stochastic forward model.

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

Treesearch

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

2015-01-01

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

Using Playing Cards to Simulate a Molecular Clock

ERIC Educational Resources Information Center

Westerling, Karin E.

2008-01-01

Changes in DNA base-repair may serve as an indicator of the time elapsed since divergence from a common ancestor. DNA sequences can now be analyzed. The simulation presented in this article allows students to observe the accumulation of changes in a randomly mutating sequence of playing cards. The cards are analogous to DNA nucleotide or protein…

3-d brownian motion simulator for high-sensitivity nanobiotechnological applications.

PubMed

Toth, Arpád; Banky, Dániel; Grolmusz, Vince

2011-12-01

A wide variety of nanobiotechnologic applications are being developed for nanoparticle based in vitro diagnostic and imaging systems. Some of these systems make possible highly sensitive detection of molecular biomarkers. Frequently, the very low concentration of the biomarkers makes impossible the classical, partial differential equation-based mathematical simulation of the motion of the nanoparticles involved. We present a three-dimensional Brownian motion simulation tool for the prediction of the movement of nanoparticles in various thermal, viscosity, and geometric settings in a rectangular cuvette. For nonprofit users the server is freely available at the site http://brownian.pitgroup.org.

CHARMM-GUI 10 Years for Biomolecular Modeling and Simulation

PubMed Central

Jo, Sunhwan; Cheng, Xi; Lee, Jumin; Kim, Seonghoon; Park, Sang-Jun; Patel, Dhilon S.; Beaven, Andrew H.; Lee, Kyu Il; Rui, Huan; Roux, Benoît; MacKerell, Alexander D.; Klauda, Jeffrey B.; Qi, Yifei

2017-01-01

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the molecular details of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. PMID:27862047

A molecular dynamics study of polymer/graphene interfacial systems

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

Rissanou, Anastassia N.; Harmandaris, Vagelis

2014-05-15

Graphene based polymer nanocomposites are hybrid materials with a very broad range of technological applications. In this work, we study three hybrid polymer/graphene interfacial systems (polystyrene/graphene, poly(methyl methacrylate)/graphene and polyethylene/graphene) through detailed atomistic molecular dynamics (MD) simulations. Density profiles, structural characteristics and mobility aspects are being examined at the molecular level for all model systems. In addition, we compare the properties of the hybrid systems to the properties of the corresponding bulk ones, as well as to theoretical predictions.

An accelerated algorithm for discrete stochastic simulation of reaction-diffusion systems using gradient-based diffusion and tau-leaping.

PubMed

Koh, Wonryull; Blackwell, Kim T

2011-04-21

Stochastic simulation of reaction-diffusion systems enables the investigation of stochastic events arising from the small numbers and heterogeneous distribution of molecular species in biological cells. Stochastic variations in intracellular microdomains and in diffusional gradients play a significant part in the spatiotemporal activity and behavior of cells. Although an exact stochastic simulation that simulates every individual reaction and diffusion event gives a most accurate trajectory of the system's state over time, it can be too slow for many practical applications. We present an accelerated algorithm for discrete stochastic simulation of reaction-diffusion systems designed to improve the speed of simulation by reducing the number of time-steps required to complete a simulation run. This method is unique in that it employs two strategies that have not been incorporated in existing spatial stochastic simulation algorithms. First, diffusive transfers between neighboring subvolumes are based on concentration gradients. This treatment necessitates sampling of only the net or observed diffusion events from higher to lower concentration gradients rather than sampling all diffusion events regardless of local concentration gradients. Second, we extend the non-negative Poisson tau-leaping method that was originally developed for speeding up nonspatial or homogeneous stochastic simulation algorithms. This method calculates each leap time in a unified step for both reaction and diffusion processes while satisfying the leap condition that the propensities do not change appreciably during the leap and ensuring that leaping does not cause molecular populations to become negative. Numerical results are presented that illustrate the improvement in simulation speed achieved by incorporating these two new strategies.

Construction of the Free Energy Landscape of Peptide Aggregation from Molecular Dynamics Simulations.

PubMed

Riccardi, Laura; Nguyen, Phuong H; Stock, Gerhard

2012-04-10

To describe the structure and dynamics of oligomers during peptide aggregation, a method is proposed that considers both the intramolecular and intermolecular structures of the multimolecule system and correctly accounts for its degeneracy. The approach is based on the "by-parts" strategy, which partitions a complex molecular system into parts, determines the metastable conformational states of each part, and describes the overall conformational state of the system in terms of a product basis of the states of the parts. Starting from a molecular dynamics simulation of n molecules, the method consists of three steps: (i) characterization of the intramolecular structure, that is, of the conformational states of a single molecule in the presence of the other molecules (e.g., β-strand or random coil); (ii) characterization of the intermolecular structure through the identification of all occurring aggregate states of the peptides (dimers, trimers, etc.); and (iii) construction of the overall conformational states of the system in terms of a product basis of the n "single-molecule" states and the aggregate states. Considering the Alzheimer β-amyloid peptide fragment Aβ16-22 as a first application, about 700 overall conformational states of the trimer (Aβ16-22)3 were constructed from all-atom molecular dynamics simulation in explicit water. Based on these states, a transition network reflecting the free energy landscape of the aggregation process can be constructed that facilitates the identification of the aggregation pathways.

Molecular dynamics simulations and photoluminescence measurements of annealed ZnO surfaces

NASA Astrophysics Data System (ADS)

Min, Tjun Kit; Yoon, Tiem Leong; Ling, Chuo Ann; Mahmud, Shahrom; Lim, Thong Leng; Saw, Kim Guan

2017-06-01

The effect of thermal annealing on wurtzite ZnO, terminated by two surfaces, (000 1 bar) (which is oxygen-terminated) and (0 0 0 1) (which is Zn-terminated), is investigated via molecular dynamics simulation using reactive force field (ReaxFF). As a result of annealing at a threshold temperature range of 700 K