Evaluation of a grid based molecular dynamics approach for polypeptide simulations.

PubMed

Merelli, Ivan; Morra, Giulia; Milanesi, Luciano

2007-09-01

Molecular dynamics is very important for biomedical research because it makes possible simulation of the behavior of a biological macromolecule in silico. However, molecular dynamics is computationally rather expensive: the simulation of some nanoseconds of dynamics for a large macromolecule such as a protein takes very long time, due to the high number of operations that are needed for solving the Newton's equations in the case of a system of thousands of atoms. In order to obtain biologically significant data, it is desirable to use high-performance computation resources to perform these simulations. Recently, a distributed computing approach based on replacing a single long simulation with many independent short trajectories has been introduced, which in many cases provides valuable results. This study concerns the development of an infrastructure to run molecular dynamics simulations on a grid platform in a distributed way. The implemented software allows the parallel submission of different simulations that are singularly short but together bring important biological information. Moreover, each simulation is divided into a chain of jobs to avoid data loss in case of system failure and to contain the dimension of each data transfer from the grid. The results confirm that the distributed approach on grid computing is particularly suitable for molecular dynamics simulations thanks to the elevated scalability.

General framework for constraints in molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Kneller, Gerald R.

2017-06-01

The article presents a theoretical framework for molecular dynamics simulations of complex systems subject to any combination of holonomic and non-holonomic constraints. Using the concept of constrained inverse matrices both the particle accelerations and the associated constraint forces can be determined from given external forces and kinematical conditions. The formalism enables in particular the construction of explicit kinematical conditions which lead to the well-known Nosé-Hoover type equations of motion for the simulation of non-standard molecular dynamics ensembles. Illustrations are given for a few examples and an outline is presented for a numerical implementation of the method.

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.

Kinetics from Replica Exchange Molecular Dynamics Simulations.

PubMed

Stelzl, Lukas S; Hummer, Gerhard

2017-08-08

Transitions between metastable states govern many fundamental processes in physics, chemistry and biology, from nucleation events in phase transitions to the folding of proteins. The free energy surfaces underlying these processes can be obtained from simulations using enhanced sampling methods. However, their altered dynamics makes kinetic and mechanistic information difficult or impossible to extract. Here, we show that, with replica exchange molecular dynamics (REMD), one can not only sample equilibrium properties but also extract kinetic information. For systems that strictly obey first-order kinetics, the procedure to extract rates is rigorous. For actual molecular systems whose long-time dynamics are captured by kinetic rate models, accurate rate coefficients can be determined from the statistics of the transitions between the metastable states at each replica temperature. We demonstrate the practical applicability of the procedure by constructing master equation (Markov state) models of peptide and RNA folding from REMD simulations.

Molecular dynamics simulations using temperature-enhanced essential dynamics replica exchange.

PubMed

Kubitzki, Marcus B; de Groot, Bert L

2007-06-15

Today's standard molecular dynamics simulations of moderately sized biomolecular systems at full atomic resolution are typically limited to the nanosecond timescale and therefore suffer from limited conformational sampling. Efficient ensemble-preserving algorithms like replica exchange (REX) may alleviate this problem somewhat but are still computationally prohibitive due to the large number of degrees of freedom involved. Aiming at increased sampling efficiency, we present a novel simulation method combining the ideas of essential dynamics and REX. Unlike standard REX, in each replica only a selection of essential collective modes of a subsystem of interest (essential subspace) is coupled to a higher temperature, with the remainder of the system staying at a reference temperature, T(0). This selective excitation along with the replica framework permits efficient approximate ensemble-preserving conformational sampling and allows much larger temperature differences between replicas, thereby considerably enhancing sampling efficiency. Ensemble properties and sampling performance of the method are discussed using dialanine and guanylin test systems, with multi-microsecond molecular dynamics simulations of these test systems serving as references.

Accelerated molecular dynamics simulations of protein folding.

PubMed

Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

2015-07-30

Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

Molecular Dynamics of Dense Fluids: Simulation-Theory Symbiosis

NASA Astrophysics Data System (ADS)

Yip, Sidney

35 years ago Berni J. Alder showed the Boltzmann-Enskog kinetic theory failed to adequately account for the viscosity of fluids near solid density as determined by molecular dynamics simulation. This work, along with other notable simulation findings, provided great stimulus to the statistical mechanical studies of transport phenomena, particularly in dealing with collective effects in the time correlation functions of liquids. An extended theoretical challenge that remains partially resolved at best is the shear viscosity of supercooled liquids. How can one give a unified explanation of the so-called fragile and strong characteristic temperature behavior, with implications for the dynamics of glass transition? In this tribute on the occasion of his 90th birthday symposium, we recount a recent study where simulation, combined with heuristic (transition-state) and first principles (linear response) theories, identifies the molecular mechanisms governing glassy-state relaxation. Such an interplay between simulation and theory is progress from the early days; instead of simulation challenging theory, now simulation and theory complement each other.

Ultrafast spectroscopy reveals subnanosecond peptide conformational dynamics and validates molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Spörlein, Sebastian; Carstens, Heiko; Satzger, Helmut; Renner, Christian; Behrendt, Raymond; Moroder, Luis; Tavan, Paul; Zinth, Wolfgang; Wachtveitl, Josef

2002-06-01

Femtosecond time-resolved spectroscopy on model peptides with built-in light switches combined with computer simulation of light-triggered motions offers an attractive integrated approach toward the understanding of peptide conformational dynamics. It was applied to monitor the light-induced relaxation dynamics occurring on subnanosecond time scales in a peptide that was backbone-cyclized with an azobenzene derivative as optical switch and spectroscopic probe. The femtosecond spectra permit the clear distinguishing and characterization of the subpicosecond photoisomerization of the chromophore, the subsequent dissipation of vibrational energy, and the subnanosecond conformational relaxation of the peptide. The photochemical cis/trans-isomerization of the chromophore and the resulting peptide relaxations have been simulated with molecular dynamics calculations. The calculated reaction kinetics, as monitored by the energy content of the peptide, were found to match the spectroscopic data. Thus we verify that all-atom molecular dynamics simulations can quantitatively describe the subnanosecond conformational dynamics of peptides, strengthening confidence in corresponding predictions for longer time scales.

Structure and dynamics of complex liquid water: Molecular dynamics simulation

NASA Astrophysics Data System (ADS)

S, Indrajith V.; Natesan, Baskaran

2015-06-01

We have carried out detailed structure and dynamical studies of complex liquid water using molecular dynamics simulations. Three different model potentials, namely, TIP3P, TIP4P and SPC-E have been used in the simulations, in order to arrive at the best possible potential function that could reproduce the structure of experimental bulk water. All the simulations were performed in the NVE micro canonical ensemble using LAMMPS. The radial distribution functions, gOO, gOH and gHH and the self diffusion coefficient, Ds, were calculated for all three models. We conclude from our results that the structure and dynamical parameters obtained for SPC-E model matched well with the experimental values, suggesting that among the models studied here, the SPC-E model gives the best structure and dynamics of bulk water.

Enhanced sampling techniques in molecular dynamics simulations of biological systems.

PubMed

Bernardi, Rafael C; Melo, Marcelo C R; Schulten, Klaus

2015-05-01

Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

Dynamics of Nanoscale Grain-Boundary Decohesion in Aluminum by Molecular-Dynamics Simulation

NASA Technical Reports Server (NTRS)

Yamakov, V.; Saether, E.; Phillips, D. R.; Glaessegen, E. H.

2007-01-01

The dynamics and energetics of intergranular crack growth along a flat grain boundary in aluminum is studied by a molecular-dynamics simulation model for crack propagation under steady-state conditions. Using the ability of the molecular-dynamics simulation to identify atoms involved in different atomistic mechanisms, it was possible to identify the energy contribution of different processes taking place during crack growth. The energy contributions were divided as: elastic energy, defined as the potential energy of the atoms in fcc crystallographic state; and plastically stored energy, the energy of stacking faults and twin boundaries; grain-boundary and surface energy. In addition, monitoring the amount of heat exchange with the molecular-dynamics thermostat gives the energy dissipated as heat in the system. The energetic analysis indicates that the majority of energy in a fast growing crack is dissipated as heat. This dissipation increases linearly at low speed, and faster than linear at speeds approaching 1/3 the Rayleigh wave speed when the crack tip becomes dynamically unstable producing periodic dislocation bursts until the crack is blunted.

Easy GROMACS: A Graphical User Interface for GROMACS Molecular Dynamics Simulation Package

NASA Astrophysics Data System (ADS)

Dizkirici, Ayten; Tekpinar, Mustafa

2015-03-01

GROMACS is a widely used molecular dynamics simulation package. Since it is a command driven program, it is difficult to use this program for molecular biologists, biochemists, new graduate students and undergraduate researchers who are interested in molecular dynamics simulations. To alleviate the problem for those researchers, we wrote a graphical user interface that simplifies protein preparation for a classical molecular dynamics simulation. Our program can work with various GROMACS versions and it can perform essential analyses of GROMACS trajectories as well as protein preparation. We named our open source program `Easy GROMACS'. Easy GROMACS can give researchers more time for scientific research instead of dealing with technical intricacies.

Characterizing rare-event property distributions via replicate molecular dynamics simulations of proteins.

PubMed

Krishnan, Ranjani; Walton, Emily B; Van Vliet, Krystyn J

2009-11-01

As computational resources increase, molecular dynamics simulations of biomolecules are becoming an increasingly informative complement to experimental studies. In particular, it has now become feasible to use multiple initial molecular configurations to generate an ensemble of replicate production-run simulations that allows for more complete characterization of rare events such as ligand-receptor unbinding. However, there are currently no explicit guidelines for selecting an ensemble of initial configurations for replicate simulations. Here, we use clustering analysis and steered molecular dynamics simulations to demonstrate that the configurational changes accessible in molecular dynamics simulations of biomolecules do not necessarily correlate with observed rare-event properties. This informs selection of a representative set of initial configurations. We also employ statistical analysis to identify the minimum number of replicate simulations required to sufficiently sample a given biomolecular property distribution. Together, these results suggest a general procedure for generating an ensemble of replicate simulations that will maximize accurate characterization of rare-event property distributions in biomolecules.

A fast recursive algorithm for molecular dynamics simulation

NASA Technical Reports Server (NTRS)

Jain, A.; Vaidehi, N.; Rodriguez, G.

1993-01-01

The present recursive algorithm for solving molecular systems' dynamical equations of motion employs internal variable models that reduce such simulations' computation time by an order of magnitude, relative to Cartesian models. Extensive use is made of spatial operator methods recently developed for analysis and simulation of the dynamics of multibody systems. A factor-of-450 speedup over the conventional O(N-cubed) algorithm is demonstrated for the case of a polypeptide molecule with 400 residues.

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.

Molecular dynamics simulations on PGLa using NMR orientational constraints.

PubMed

Sternberg, Ulrich; Witter, Raiker

2015-11-01

NMR data obtained by solid state NMR from anisotropic samples are used as orientational constraints in molecular dynamics simulations for determining the structure and dynamics of the PGLa peptide within a membrane environment. For the simulation the recently developed molecular dynamics with orientational constraints technique (MDOC) is used. This method introduces orientation dependent pseudo-forces into the COSMOS-NMR force field. Acting during a molecular dynamics simulation these forces drive molecular rotations, re-orientations and folding in such a way that the motional time-averages of the tensorial NMR properties are consistent with the experimentally measured NMR parameters. This MDOC strategy does not depend on the initial choice of atomic coordinates, and is in principle suitable for any flexible and mobile kind of molecule; and it is of course possible to account for flexible parts of peptides or their side-chains. MDOC has been applied to the antimicrobial peptide PGLa and a related dimer model. With these simulations it was possible to reproduce most NMR parameters within the experimental error bounds. The alignment, conformation and order parameters of the membrane-bound molecule and its dimer were directly derived with MDOC from the NMR data. Furthermore, this new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of the dimer systems. It was demonstrated the deuterium splittings measured at the peptide to lipid ratio of 1/50 are consistent with a membrane spanning orientation of the peptide.

Rotational Dynamics of Proteins from Spin Relaxation Times and Molecular Dynamics Simulations.

PubMed

Ollila, O H Samuli; Heikkinen, Harri A; Iwaï, Hideo

2018-06-14

Conformational fluctuations and rotational tumbling of proteins can be experimentally accessed with nuclear spin relaxation experiments. However, interpretation of molecular dynamics from the experimental data is often complicated, especially for molecules with anisotropic shape. Here, we apply classical molecular dynamics simulations to interpret the conformational fluctuations and rotational tumbling of proteins with arbitrarily anisotropic shape. The direct calculation of spin relaxation times from simulation data did not reproduce the experimental data. This was successfully corrected by scaling the overall rotational diffusion coefficients around the protein inertia axes with a constant factor. The achieved good agreement with experiments allowed the interpretation of the internal and overall dynamics of proteins with significantly anisotropic shape. The overall rotational diffusion was found to be Brownian, having only a short subdiffusive region below 0.12 ns. The presented methodology can be applied to interpret rotational dynamics and conformation fluctuations of proteins with arbitrary anisotropic shape. However, a water model with more realistic dynamical properties is probably required for intrinsically disordered proteins.

Molecular dynamics simulation of β₂-microglobulin in denaturing and stabilizing conditions.

PubMed

Fogolari, Federico; Corazza, Alessandra; Varini, Nicola; Rotter, Matteo; Gumral, Devrim; Codutti, Luca; Rennella, Enrico; Viglino, Paolo; Bellotti, Vittorio; Esposito, Gennaro

2011-03-01

β₂-Microglobulin has been a model system for the study of fibril formation for 20 years. The experimental study of β₂-microglobulin structure, dynamics, and thermodynamics in solution, at atomic detail, along the pathway leading to fibril formation is difficult because the onset of disorder and aggregation prevents signal resolution in Nuclear Magnetic Resonance experiments. Moreover, it is difficult to characterize conformers in exchange equilibrium. To gain insight (at atomic level) on processes for which experimental information is available at molecular or supramolecular level, molecular dynamics simulations have been widely used in the last decade. Here, we use molecular dynamics to address three key aspects of β₂-microglobulin, which are known to be relevant to amyloid formation: (1) 60 ns molecular dynamics simulations of β₂-microglobulin in trifluoroethanol and in conditions mimicking low pH are used to study the behavior of the protein in environmental conditions that are able to trigger amyloid formation; (2) adaptive biasing force molecular dynamics simulation is used to force cis-trans isomerization at Proline 32 and to calculate the relative free energy in the folded and unfolded state. The native-like trans-conformer (known as intermediate 2 and determining the slow phase of refolding), is simulated for 10 ns, detailing the possible link between cis-trans isomerization and conformational disorder; (3) molecular dynamics simulation of highly concentrated doxycycline (a molecule able to suppress fibril formation) in the presence of β₂-microglobulin provides details of the binding modes of the drug and a rationale for its effect. Copyright © 2010 Wiley-Liss, Inc.

Insights from molecular dynamics simulations for computational protein design.

PubMed

Childers, Matthew Carter; Daggett, Valerie

2017-02-01

A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.

Insights from molecular dynamics simulations for computational protein design

PubMed Central

Childers, Matthew Carter; Daggett, Valerie

2017-01-01

A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures. PMID:28239489

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.

Molecular dynamics simulations of methane hydrate decomposition.

PubMed

Myshakin, Evgeniy M; Jiang, Hao; Warzinski, Robert P; Jordan, Kenneth D

2009-03-12

Molecular dynamics simulations have been carried out to study decomposition of methane hydrate at different cage occupancies. The decomposition rate is found to depend sensitively on the hydration number. The rate of the destruction of the cages displays Arrhenius behavior, consistent with an activated mechanism. During the simulations, reversible formation of partial water cages around methane molecules in the liquid was observed at the interface at temperatures above the computed hydrate decomposition temperature.

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.

Molecular mechanisms of cryoprotection in aqueous proline: light scattering and molecular dynamics simulations.

PubMed

Troitzsch, R Z; Vass, H; Hossack, W J; Martyna, G J; Crain, J

2008-04-10

Free proline amino acid is a natural cryoprotectant expressed by numerous organisms under low-temperature stress. Previous reports have suggested that complex assemblies underlie its functional properties. We investigate here aqueous proline solutions as a function of temperature using combinations of Raman spectroscopy, Rayleigh-Brillouin light scattering, and molecular dynamics simulations with the view to revealing the molecular origins of the mixtures' functionality as a cryoprotectant. The evolution of the Brillouin frequency shifts and line widths with temperature shows that, above a critical proline concentration, the water-like dynamics is suppressed and viscoelastic behavior emerges: Here, the Landau-Placzek ratio also shows a temperature-independent maximum arising from concentration fluctuations. Molecular dynamics simulations reveal that the water-water correlations in the mixtures depend much more weakly on temperature than does bulk water. By contrast, the water OH Raman bands exhibit strong red-shifts on cooling similar to those seen in ices; however, no evidence of ice lattice phonons is observed in the low-frequency spectrum. We attribute this primarily to enhanced proline-water hydrogen bonding. In general, the picture that emerges is that aqueous proline is a heterogeneous mixture on molecular length scales (characterized by significant concentration fluctuations rather than well-defined aggregates). Simulations reveal that proline also appears to suppress the normal dependence of water structure on temperature and preserves the ambient-temperature correlations even in very cold solutions. The water structure in cold proline solutions therefore appears to be similar to that at a higher effective temperature. This, coupled with the emergence of glassy dynamics offers a molecular explanation for the functional properties of proline as a cryoprotectant without the need to invoke previously proposed complex aggregates.

Nonadiabatic molecular dynamics simulations: synergies between theory and experiments.

PubMed

Tavernelli, Ivano

2015-03-17

Recent developments in nonadiabatic dynamics enabled ab inito simulations of complex ultrafast processes in the condensed phase. These advances have opened new avenues in the study of many photophysical and photochemical reactions triggered by the absorption of electromagnetic radiation. In particular, theoretical investigations can be combined with the most sophisticated femtosecond experimental techniques to guide the interpretation of measured time-resolved observables. At the same time, the availability of experimental data at high (spatial and time) resolution offers a unique opportunity for the benchmarking and the improvement of those theoretical models used to describe complex molecular systems in their natural environment. The established synergy between theory and experiments can produce a better understanding of new ultrafast physical and chemical processes at atomistic scale resolution. Furthermore, reliable ab inito molecular dynamics simulations can already be successfully employed as predictive tools to guide new experiments as well as the design of novel and better performing materials. In this paper, I will give a concise account on the state of the art of molecular dynamics simulations of complex molecular systems in their excited states. The principal aim of this approach is the description of a given system of interest under the most realistic ambient conditions including all environmental effects that influence experiments, for instance, the interaction with the solvent and with external time-dependent electric fields, temperature, and pressure. To this end, time-dependent density functional theory (TDDFT) is among the most efficient and accurate methods for the representation of the electronic dynamics, while trajectory surface hopping gives a valuable representation of the nuclear quantum dynamics in the excited states (including nonadiabatic effects). Concerning the environment and its effects on the dynamics, the quantum mechanics/molecular

Molecular Dynamics Simulations of Nucleic Acids. From Tetranucleotides to the Ribosome.

PubMed

Šponer, Jiří; Banáš, Pavel; Jurečka, Petr; Zgarbová, Marie; Kührová, Petra; Havrila, Marek; Krepl, Miroslav; Stadlbauer, Petr; Otyepka, Michal

2014-05-15

We present a brief overview of explicit solvent molecular dynamics (MD) simulations of nucleic acids. We explain physical chemistry limitations of the simulations, namely, the molecular mechanics (MM) force field (FF) approximation and limited time scale. Further, we discuss relations and differences between simulations and experiments, compare standard and enhanced sampling simulations, discuss the role of starting structures, comment on different versions of nucleic acid FFs, and relate MM computations with contemporary quantum chemistry. Despite its limitations, we show that MD is a powerful technique for studying the structural dynamics of nucleic acids with a fast growing potential that substantially complements experimental results and aids their interpretation.

Molecular Dynamics Simulations of Shear Induced Transformations in Nitromethane

NASA Astrophysics Data System (ADS)

Larentzos, James; Steele, Brad

2017-06-01

Recent experiments demonstrate that NM undergoes explosive chemical initiation under compressive shear stress. The atomistic dynamics of the shear response of single-crystalline and bi-crystalline nitromethane (NM) are simulated using molecular dynamics simulations under high pressure conditions to aid in interpreting these experiments. The atomic interactions are described using a recently re-optimized ReaxFF-lg potential trained specifically for NM under pressure. The simulations demonstrate that the NM crystal transforms into a disordered state upon sufficient application of shear stress; its maximum value, shear angle, and atomic-scale dynamics being highly dependent on crystallographic orientation of the applied shear. Shear simulations in bi-crystalline NM show more complex behavior resulting in the appearance of the disordered state at the grain boundary.

Molecular Dynamics Simulations of Shear Induced Transformations in Nitromethane

NASA Astrophysics Data System (ADS)

Larentzos, James; Steele, Brad

Recent experiments demonstrate that NM undergoes explosive chemical initiation under compressive shear stress. The atomistic dynamics of the shear response of single-crystalline and bi-crystalline nitromethane (NM) are simulated using molecular dynamics simulations under high pressure conditions to aid in interpreting these experiments. The atomic interactions are described using a recently re-optimized ReaxFF-lg potential trained specifically for NM under pressure. The simulations demonstrate that the NM crystal transforms into a disordered state upon sufficient application of shear stress; its maximum value, shear angle, and atomic-scale dynamics being highly dependent on crystallographic orientation of the applied shear. Shear simulations in bi-crystalline NM show more complex behavior resulting in the appearance of the disordered state at the grain boundary.

Coupled binding-bending-folding: The complex conformational dynamics of protein-DNA binding studied by atomistic molecular dynamics simulations.

PubMed

van der Vaart, Arjan

2015-05-01

Protein-DNA binding often involves dramatic conformational changes such as protein folding and DNA bending. While thermodynamic aspects of this behavior are understood, and its biological function is often known, the mechanism by which the conformational changes occur is generally unclear. By providing detailed structural and energetic data, molecular dynamics simulations have been helpful in elucidating and rationalizing protein-DNA binding. This review will summarize recent atomistic molecular dynamics simulations of the conformational dynamics of DNA and protein-DNA binding. A brief overview of recent developments in DNA force fields is given as well. Simulations have been crucial in rationalizing the intrinsic flexibility of DNA, and have been instrumental in identifying the sequence of binding events, the triggers for the conformational motion, and the mechanism of binding for a number of important DNA-binding proteins. Molecular dynamics simulations are an important tool for understanding the complex binding behavior of DNA-binding proteins. With recent advances in force fields and rapid increases in simulation time scales, simulations will become even more important for future studies. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014. Published by Elsevier B.V.

Thermalized Drude Oscillators with the LAMMPS Molecular Dynamics Simulator.

PubMed

Dequidt, Alain; Devémy, Julien; Pádua, Agílio A H

2016-01-25

LAMMPS is a very customizable molecular dynamics simulation software, which can be used to simulate a large diversity of systems. We introduce a new package for simulation of polarizable systems with LAMMPS using thermalized Drude oscillators. The implemented functionalities are described and are illustrated by examples. The implementation was validated by comparing simulation results with published data and using a reference software. Computational performance is also analyzed.

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.

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.

Nonholonomic Hamiltonian Method for Molecular Dynamics Simulations of Reacting Shocks

NASA Astrophysics Data System (ADS)

Fahrenthold, Eric; Bass, Joseph

2015-06-01

Conventional molecular dynamics simulations of reacting shocks employ a holonomic Hamiltonian formulation: the breaking and forming of covalent bonds is described by potential functions. In general these potential functions: (a) are algebraically complex, (b) must satisfy strict smoothness requirements, and (c) contain many fitted parameters. In recent research the authors have developed a new noholonomic formulation of reacting molecular dynamics. In this formulation bond orders are determined by rate equations and the bonding-debonding process need not be described by differentiable functions. This simplifies the representation of complex chemistry and reduces the number of fitted model parameters. Example applications of the method show molecular level shock to detonation simulations in nitromethane and RDX. Research supported by the Defense Threat Reduction Agency.

Solute Dynamics In Liquid Systems: Experiments and Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Rumble, Christopher A.

dependent on both solvation dynamics and solvent polarity. Using acetonitrile/propylene carbonate mixtures, which have nearly identical polarity but have solvation times that vary over an order of magnitude, we were able to demonstrate that fast solvation dynamics introduces a barrier to the reaction and slows down the proton transfer rate. In Chapter 6 the intramolecular electron transfer reaction of 9-(4-biphenyl)-10-methylacridinium (BPAc+) is studied in mixtures of an ionic liquid and acetonitrile. Using KGE and picosecond time-correlated single photon counting measurements we show that the BPAc+ electron transfer rate is highly correlated with the mixture solvation time, consistent with rates observed in conventional solvents. Finally, Chapters 7 and 8 are an exploration of solute rotational dynamics in ionic liquids (ILs). Solute rotations in these unique solvents have been shown to be non-diffusive and poorly predicted by hydrodynamic theories of friction. We set out to explore the mechanisms of solute rotation in ILs using a combination of experimental methods and molecular dynamics (MD) simulations. In Chapter 7 the rotational dynamics of benzene and the IL cation 1- ethyl-3-methylimidizolium are studied using a combination of 2H longitudinal spin relaxation (T1) measurements and MD simulations. Using the simulations for guidance, we were able to interpret T1 measurements outside of the extreme narrowing limit. After the realism of the simulations was validated, they were then used to show that benzene exhibits markedly different dynamics for 'spinning' about the C6 symmetry axis and 'tumbling' (rotation of the C6 axis), and that large amplitude jump motions and orientational caging are prominent features of benzene's rotations in ILs. Chapter 8 extends the benzene work to examine the effect of molecular size and charge distribution on solute rotational dynamics in ILs. Combining fluorescence anisotropy and T1 relaxation measurements with MD simulations of a

Coupling all-atom molecular dynamics simulations of ions in water with Brownian dynamics.

PubMed

Erban, Radek

2016-02-01

Molecular dynamics (MD) simulations of ions (K + , Na + , Ca 2+ and Cl - ) in aqueous solutions are investigated. Water is described using the SPC/E model. A stochastic coarse-grained description for ion behaviour is presented and parametrized using MD simulations. It is given as a system of coupled stochastic and ordinary differential equations, describing the ion position, velocity and acceleration. The stochastic coarse-grained model provides an intermediate description between all-atom MD simulations and Brownian dynamics (BD) models. It is used to develop a multiscale method which uses all-atom MD simulations in parts of the computational domain and (less detailed) BD simulations in the remainder of the domain.

Prediction of glass transition temperature of freeze-dried formulations by molecular dynamics simulation.

PubMed

Yoshioka, Sumie; Aso, Yukio; Kojima, Shigeo

2003-06-01

To examine whether the glass transition temperature (Tg) of freeze-dried formulations containing polymer excipients can be accurately predicted by molecular dynamics simulation using software currently available on the market. Molecular dynamics simulations were carried out for isomaltodecaose, a fragment of dextran, and alpha-glucose, the repeated unit of dextran. in the presence or absence of water molecules. Estimated values of Tg were compared with experimental values obtained by differential scanning calorimetry (DSC). Isothermal-isobaric molecular dynamics simulations (NPTMD) and isothermal molecular dynamics simulations at a constant volume (NVTMD) were carried out using the software package DISCOVER (Material Studio) with the Polymer Consortium Force Field. Mean-squared displacement and radial distribution function were calculated. NVTMD using the values of density obtained by NPTMD provided the diffusivity of glucose-ring oxygen and water oxygen in amorphous alpha-glucose and isomaltodecaose, which exhibited a discontinuity in temperature dependence due to glass transition. Tg was estimated to be approximately 400K and 500K for pure amorphous a-glucose and isomaltodecaose, respectively, and in the presence of one water molecule per glucose unit, Tg was 340K and 360K, respectively. Estimated Tg values were higher than experimentally determined values because of the very fast cooling rates in the simulations. However, decreases in Tg on hydration and increases in Tg associated with larger fragment size could be demonstrated. The results indicate that molecular dynamics simulation is a useful method for investigating the effects of hydration and molecular weight on the Tg of lyophilized formulations containing polymer excipients. although the relationship between cooling rates and Tg must first be elucidated to predict Tg vales observed by DSC measurement. January 16.

Validating clustering of molecular dynamics simulations using polymer models.

PubMed

Phillips, Joshua L; Colvin, Michael E; Newsam, Shawn

2011-11-14

Molecular dynamics (MD) simulation is a powerful technique for sampling the meta-stable and transitional conformations of proteins and other biomolecules. Computational data clustering has emerged as a useful, automated technique for extracting conformational states from MD simulation data. Despite extensive application, relatively little work has been done to determine if the clustering algorithms are actually extracting useful information. A primary goal of this paper therefore is to provide such an understanding through a detailed analysis of data clustering applied to a series of increasingly complex biopolymer models. We develop a novel series of models using basic polymer theory that have intuitive, clearly-defined dynamics and exhibit the essential properties that we are seeking to identify in MD simulations of real biomolecules. We then apply spectral clustering, an algorithm particularly well-suited for clustering polymer structures, to our models and MD simulations of several intrinsically disordered proteins. Clustering results for the polymer models provide clear evidence that the meta-stable and transitional conformations are detected by the algorithm. The results for the polymer models also help guide the analysis of the disordered protein simulations by comparing and contrasting the statistical properties of the extracted clusters. We have developed a framework for validating the performance and utility of clustering algorithms for studying molecular biopolymer simulations that utilizes several analytic and dynamic polymer models which exhibit well-behaved dynamics including: meta-stable states, transition states, helical structures, and stochastic dynamics. We show that spectral clustering is robust to anomalies introduced by structural alignment and that different structural classes of intrinsically disordered proteins can be reliably discriminated from the clustering results. To our knowledge, our framework is the first to utilize model polymers

Validating clustering of molecular dynamics simulations using polymer models

PubMed Central

2011-01-01

Background Molecular dynamics (MD) simulation is a powerful technique for sampling the meta-stable and transitional conformations of proteins and other biomolecules. Computational data clustering has emerged as a useful, automated technique for extracting conformational states from MD simulation data. Despite extensive application, relatively little work has been done to determine if the clustering algorithms are actually extracting useful information. A primary goal of this paper therefore is to provide such an understanding through a detailed analysis of data clustering applied to a series of increasingly complex biopolymer models. Results We develop a novel series of models using basic polymer theory that have intuitive, clearly-defined dynamics and exhibit the essential properties that we are seeking to identify in MD simulations of real biomolecules. We then apply spectral clustering, an algorithm particularly well-suited for clustering polymer structures, to our models and MD simulations of several intrinsically disordered proteins. Clustering results for the polymer models provide clear evidence that the meta-stable and transitional conformations are detected by the algorithm. The results for the polymer models also help guide the analysis of the disordered protein simulations by comparing and contrasting the statistical properties of the extracted clusters. Conclusions We have developed a framework for validating the performance and utility of clustering algorithms for studying molecular biopolymer simulations that utilizes several analytic and dynamic polymer models which exhibit well-behaved dynamics including: meta-stable states, transition states, helical structures, and stochastic dynamics. We show that spectral clustering is robust to anomalies introduced by structural alignment and that different structural classes of intrinsically disordered proteins can be reliably discriminated from the clustering results. To our knowledge, our framework is the

Ice formation on kaolinite: Insights from molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sosso, Gabriele C.; Tribello, Gareth A.; Zen, Andrea; Pedevilla, Philipp; Michaelides, Angelos

2016-12-01

The formation of ice affects many aspects of our everyday life as well as important technologies such as cryotherapy and cryopreservation. Foreign substances almost always aid water freezing through heterogeneous ice nucleation, but the molecular details of this process remain largely unknown. In fact, insight into the microscopic mechanism of ice formation on different substrates is difficult to obtain even if state-of-the-art experimental techniques are used. At the same time, atomistic simulations of heterogeneous ice nucleation frequently face extraordinary challenges due to the complexity of the water-substrate interaction and the long time scales that characterize nucleation events. Here, we have investigated several aspects of molecular dynamics simulations of heterogeneous ice nucleation considering as a prototypical ice nucleating material the clay mineral kaolinite, which is of relevance in atmospheric science. We show via seeded molecular dynamics simulations that ice nucleation on the hydroxylated (001) face of kaolinite proceeds exclusively via the formation of the hexagonal ice polytype. The critical nucleus size is two times smaller than that obtained for homogeneous nucleation at the same supercooling. Previous findings suggested that the flexibility of the kaolinite surface can alter the time scale for ice nucleation within molecular dynamics simulations. However, we here demonstrate that equally flexible (or non flexible) kaolinite surfaces can lead to very different outcomes in terms of ice formation, according to whether or not the surface relaxation of the clay is taken into account. We show that very small structural changes upon relaxation dramatically alter the ability of kaolinite to provide a template for the formation of a hexagonal overlayer of water molecules at the water-kaolinite interface, and that this relaxation therefore determines the nucleation ability of this mineral.

Molecular dynamics simulations of aqueous solutions of ethanolamines.

PubMed

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

2006-08-03

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

MDANSE: An Interactive Analysis Environment for Molecular Dynamics Simulations.

PubMed

Goret, G; Aoun, B; Pellegrini, E

2017-01-23

The MDANSE software-Molecular Dynamics Analysis of Neutron Scattering Experiments-is presented. It is an interactive application for postprocessing molecular dynamics (MD) simulations. Given the widespread use of MD simulations in material and biomolecular sciences to get a better insight for experimental techniques such as thermal neutron scattering (TNS), the development of MDANSE has focused on providing a user-friendly, interactive, graphical user interface for analyzing many trajectories in the same session and running several analyses simultaneously independently of the interface. This first version of MDANSE already proposes a broad range of analyses, and the application has been designed to facilitate the introduction of new analyses in the framework. All this makes MDANSE a valuable tool for extracting useful information from trajectories resulting from a wide range of MD codes.

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

Exploring GPCR-Lipid Interactions by Molecular Dynamics Simulations: Excitements, Challenges, and the Way Forward.

PubMed

Sengupta, Durba; Prasanna, Xavier; Mohole, Madhura; Chattopadhyay, Amitabha

2018-06-07

Gprotein-coupled receptors (GPCRs) are seven transmembrane receptors that mediate a large number of cellular responses and are important drug targets. One of the current challenges in GPCR biology is to analyze the molecular signatures of receptor-lipid interactions and their subsequent effects on GPCR structure, organization, and function. Molecular dynamics simulation studies have been successful in predicting molecular determinants of receptor-lipid interactions. In particular, predicted cholesterol interaction sites appear to correspond well with experimentally determined binding sites and estimated time scales of association. In spite of several success stories, the methodologies in molecular dynamics simulations are still emerging. In this Feature Article, we provide a comprehensive overview of coarse-grain and atomistic molecular dynamics simulations of GPCR-lipid interaction in the context of experimental observations. In addition, we discuss the effect of secondary and tertiary structural constraints in coarse-grain simulations in the context of functional dynamics and structural plasticity of GPCRs. We envision that this comprehensive overview will help resolve differences in computational studies and provide a way forward.

Molecular dynamics simulations of hydrogen diffusion in aluminum

DOE PAGES

Zhou, X. W.; El Gabaly, F.; Stavila, V.; ...

2016-03-23

In this study, hydrogen diffusion impacts the performance of solid-state hydrogen storage materials and contributes to the embrittlement of structural materials under hydrogen-containing environments. In atomistic simulations, the diffusion energy barriers are usually calculated using molecular statics simulations where a nudged elastic band method is used to constrain a path connecting the two end points of an atomic jump. This approach requires prior knowledge of the “end points”. For alloy and defective systems, the number of possible atomic jumps with respect to local atomic configurations is tremendous. Even when these jumps can be exhaustively studied, it is still unclear howmore » they can be combined to give an overall diffusion behavior seen in experiments. Here we describe the use of molecular dynamics simulations to determine the overall diffusion energy barrier from the Arrhenius equation. This method does not require information about atomic jumps, and it has additional advantages, such as the ability to incorporate finite temperature effects and to determine the pre-exponential factor. As a test case for a generic method, we focus on hydrogen diffusion in bulk aluminum. We find that the challenge of this method is the statistical variation of the results. However, highly converged energy barriers can be achieved by an appropriate set of temperatures, output time intervals (for tracking hydrogen positions), and a long total simulation time. Our results help elucidate the inconsistencies of the experimental diffusion data published in the literature. The robust approach developed here may also open up future molecular dynamics simulations to rapidly study diffusion properties of complex material systems in multidimensional spaces involving composition and defects.« less

Ab-Initio Molecular Dynamics Simulation of Graphene Sheet

NASA Astrophysics Data System (ADS)

Kolev, S.; Balchev, I.; Cvetkov, K.; Tinchev, S.; Milenov, T.

2017-01-01

The study of graphene is important because it is a promising material for a variety of applications in the electronic industry. In the present work, the properties of а 2D periodic graphene sheet are studied with the use of ab initio molecular dynamics. DFT in the generalized gradient approximation is used in order to carry out the dynamical simulations. The PBE functional and DZVP-MOLOPT basis set are implemented in the CP2K/Quickstep package. A periodic box, consisting of 288 carbon atoms is chosen for the simulations. After geometry optimization it has dimensions 2964 x 2964 x 1500 pm and form angles of 90, 90, 60 degrees. The dynamical simulation is run for 1 ps in the NPT ensemble, at temperature T = 298.15 K. The radial distribution function shows a first peak at 142 pm, marking the bond length between carbon atoms. The density of states for the periodic systems is simulated as occupied orbitals represent the valence band and unoccupied ones the conduction band. The calculated bandgap, as expected is close to 0 eV.

Molecular dynamics simulation of low-energy recoil events in titanate pyrochlores

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

Dong, Liyuan; Setyawan, Wahyu; Li, Yuhong

2017-01-01

Molecular dynamics simulations of low-energy displacements in titanate pyrochlores have been carried out along three main directions, to determineE dfor A, Ti and O, corresponding defect configurations, and defect formation dynamics.

Molecular Dynamics Simulations of Laser Powered Carbon Nanotube Gears

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Globus, Al; Han, Jie; Chancellor, Marisa K. (Technical Monitor)

1997-01-01

Dynamics of laser powered carbon nanotube gears is investigated by molecular dynamics simulations with Brenner's hydrocarbon potential. We find that when the frequency of the laser electric field is much less than the intrinsic frequency of the carbon nanotube, the tube exhibits an oscillatory pendulam behavior. However, a unidirectional rotation of the gear with oscillating frequency is observed under conditions of resonance between the laser field and intrinsic gear frequencies. The operating conditions for stable rotations of the nanotube gears, powered by laser electric fields are explored, in these simulations.

Probing antibody internal dynamics with fluorescence anisotropy and molecular dynamics simulations.

PubMed

Kortkhonjia, Ekaterine; Brandman, Relly; Zhou, Joe Zhongxiang; Voelz, Vincent A; Chorny, Ilya; Kabakoff, Bruce; Patapoff, Thomas W; Dill, Ken A; Swartz, Trevor E

2013-01-01

The solution dynamics of antibodies are critical to antibody function. We explore the internal solution dynamics of antibody molecules through the combination of time-resolved fluorescence anisotropy experiments on IgG1 with more than two microseconds of all-atom molecular dynamics (MD) simulations in explicit water, an order of magnitude more than in previous simulations. We analyze the correlated motions with a mutual information entropy quantity, and examine state transition rates in a Markov-state model, to give coarse-grained descriptors of the motions. Our MD simulations show that while there are many strongly correlated motions, antibodies are highly flexible, with F(ab) and F(c) domains constantly forming and breaking contacts, both polar and non-polar. We find that salt bridges break and reform, and not always with the same partners. While the MD simulations in explicit water give the right time scales for the motions, the simulated motions are about 3-fold faster than the experiments. Overall, the picture that emerges is that antibodies do not simply fluctuate around a single state of atomic contacts. Rather, in these large molecules, different atoms come in contact during different motions.

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 and novel drug discovery.

PubMed

Liu, Xuewei; Shi, Danfeng; Zhou, Shuangyan; Liu, Hongli; Liu, Huanxiang; Yao, Xiaojun

2018-01-01

Molecular dynamics (MD) simulations can provide not only plentiful dynamical structural information on biomacromolecules but also a wealth of energetic information about protein and ligand interactions. Such information is very important to understanding the structure-function relationship of the target and the essence of protein-ligand interactions and to guiding the drug discovery and design process. Thus, MD simulations have been applied widely and successfully in each step of modern drug discovery. Areas covered: In this review, the authors review the applications of MD simulations in novel drug discovery, including the pathogenic mechanisms of amyloidosis diseases, virtual screening and the interaction mechanisms between drugs and targets. Expert opinion: MD simulations have been used widely in investigating the pathogenic mechanisms of diseases caused by protein misfolding, in virtual screening, and in investigating drug resistance mechanisms caused by mutations of the target. These issues are very difficult to solve by experimental methods alone. Thus, in the future, MD simulations will have wider application with the further improvement of computational capacity and the development of better sampling methods and more accurate force fields together with more efficient analysis methods.

GPCRs: What Can We Learn from Molecular Dynamics Simulations?

PubMed

Velgy, Naushad; Hedger, George; Biggin, Philip C

2018-01-01

Advances in the structural biology of G-protein Coupled Receptors have resulted in a significant step forward in our understanding of how this important class of drug targets function at the molecular level. However, it has also become apparent that they are very dynamic molecules, and moreover, that the underlying dynamics is crucial in shaping the response to different ligands. Molecular dynamics simulations can provide unique insight into the dynamic properties of GPCRs in a way that is complementary to many experimental approaches. In this chapter, we describe progress in three distinct areas that are particularly difficult to study with other techniques: atomic level investigation of the conformational changes that occur when moving between the various states that GPCRs can exist in, the pathways that ligands adopt during binding/unbinding events and finally, the influence of lipids on the conformational dynamics of GPCRs.

Molecular Dynamics Simulations of Hydrophobic Residues

NASA Astrophysics Data System (ADS)

Caballero, Diego; Zhou, Alice; Regan, Lynne; O'Hern, Corey

2013-03-01

Molecular recognition and protein-protein interactions are involved in important biological processes. However, despite recent improvements in computational methods for protein design, we still lack a predictive understanding of protein structure and interactions. To begin to address these shortcomings, we performed molecular dynamics simulations of hydrophobic residues modeled as hard spheres with stereo-chemical constraints initially at high temperature, and then quenched to low temperature to obtain local energy minima. We find that there is a range of quench rates over which the probabilities of side-chain dihedral angles for hydrophobic residues match the probabilities obtained for known protein structures. In addition, we predict the side-chain dihedral angle propensities in the core region of the proteins T4, ROP, and several mutants. These studies serve as a first step in developing the ability to quantitatively rank the energies of designed protein constructs. The success of these studies suggests that only hard-sphere dynamics with geometrical constraints are needed for accurate protein structure prediction in hydrophobic cavities and binding interfaces. NSF Grant PHY-1019147

Molecular dynamics simulation of metal nanoislands growth

NASA Astrophysics Data System (ADS)

Kapralov, N. V.; Babich, E. S.; Redkov, A. V.

2017-11-01

We present the atomistic model and the simulation of a self-assembled growth of a silver nanoisland film and small groups of nanoislands on a glass substrate after thermal poling of the glass with a profiled electrode. The calculations were performed in molecular dynamics simulator LAMMPS taking into account the diffusion of the metal atoms towards and along the glass surface and their clustering. Lennard-Jones potential was used to describe metal-metal and metal-glass interaction. The potential parameters were determined to provide qualitative coincidence of the simulated configurations of the metal nanostructures and the experimental ones, such as an isolated nanoisland, a pair and a set of three nanoislands and a “plasmonic molecule”.

Symplectic molecular dynamics simulations on specially designed parallel computers.

PubMed

Borstnik, Urban; Janezic, Dusanka

2005-01-01

We have developed a computer program for molecular dynamics (MD) simulation that implements the Split Integration Symplectic Method (SISM) and is designed to run on specialized parallel computers. The MD integration is performed by the SISM, which analytically treats high-frequency vibrational motion and thus enables the use of longer simulation time steps. The low-frequency motion is treated numerically on specially designed parallel computers, which decreases the computational time of each simulation time step. The combination of these approaches means that less time is required and fewer steps are needed and so enables fast MD simulations. We study the computational performance of MD simulation of molecular systems on specialized computers and provide a comparison to standard personal computers. The combination of the SISM with two specialized parallel computers is an effective way to increase the speed of MD simulations up to 16-fold over a single PC processor.

Faster protein folding using enhanced conformational sampling of molecular dynamics simulation.

PubMed

Kamberaj, Hiqmet

2018-05-01

In this study, we applied swarm particle-like molecular dynamics (SPMD) approach to enhance conformational sampling of replica exchange simulations. In particular, the approach showed significant improvement in sampling efficiency of conformational phase space when combined with replica exchange method (REM) in computer simulation of peptide/protein folding. First we introduce the augmented dynamical system of equations, and demonstrate the stability of the algorithm. Then, we illustrate the approach by using different fully atomistic and coarse-grained model systems, comparing them with the standard replica exchange method. In addition, we applied SPMD simulation to calculate the time correlation functions of the transitions in a two dimensional surface to demonstrate the enhancement of transition path sampling. Our results showed that folded structure can be obtained in a shorter simulation time using the new method when compared with non-augmented dynamical system. Typically, in less than 0.5 ns using replica exchange runs assuming that native folded structure is known and within simulation time scale of 40 ns in the case of blind structure prediction. Furthermore, the root mean square deviations from the reference structures were less than 2Å. To demonstrate the performance of new method, we also implemented three simulation protocols using CHARMM software. Comparisons are also performed with standard targeted molecular dynamics simulation method. Copyright © 2018 Elsevier Inc. All rights reserved.

Ensemble Sampling vs. Time Sampling in Molecular Dynamics Simulations of Thermal Conductivity

DOE PAGES

Gordiz, Kiarash; Singh, David J.; Henry, Asegun

2015-01-29

In this report we compare time sampling and ensemble averaging as two different methods available for phase space sampling. For the comparison, we calculate thermal conductivities of solid argon and silicon structures, using equilibrium molecular dynamics. We introduce two different schemes for the ensemble averaging approach, and show that both can reduce the total simulation time as compared to time averaging. It is also found that velocity rescaling is an efficient mechanism for phase space exploration. Although our methodology is tested using classical molecular dynamics, the ensemble generation approaches may find their greatest utility in computationally expensive simulations such asmore » first principles molecular dynamics. For such simulations, where each time step is costly, time sampling can require long simulation times because each time step must be evaluated sequentially and therefore phase space averaging is achieved through sequential operations. On the other hand, with ensemble averaging, phase space sampling can be achieved through parallel operations, since each ensemble is independent. For this reason, particularly when using massively parallel architectures, ensemble sampling can result in much shorter simulation times and exhibits similar overall computational effort.« less

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.

An undergraduate laboratory activity on molecular dynamics simulations.

PubMed

Spitznagel, Benjamin; Pritchett, Paige R; Messina, Troy C; Goadrich, Mark; Rodriguez, Juan

2016-01-01

Vision and Change [AAAS, 2011] outlines a blueprint for modernizing biology education by addressing conceptual understanding of key concepts, such as the relationship between structure and function. The document also highlights skills necessary for student success in 21st century Biology, such as the use of modeling and simulation. Here we describe a laboratory activity that allows students to investigate the dynamic nature of protein structure and function through the use of a modeling technique known as molecular dynamics (MD). The activity takes place over two lab periods that are 3 hr each. The first lab period unpacks the basic approach behind MD simulations, beginning with the kinematic equations that all bioscience students learn in an introductory physics course. During this period students are taught rudimentary programming skills in Python while guided through simple modeling exercises that lead up to the simulation of the motion of a single atom. In the second lab period students extend concepts learned in the first period to develop skills in the use of expert MD software. Here students simulate and analyze changes in protein conformation resulting from temperature change, solvation, and phosphorylation. The article will describe how these activities can be carried out using free software packages, including Abalone and VMD/NAMD. © 2016 The International Union of Biochemistry and Molecular Biology.

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.

Molecular dynamics simulations of β2-microglobulin interaction with hydrophobic surfaces.

PubMed

Dongmo Foumthuim, Cedrix J; Corazza, Alessandra; Esposito, Gennaro; Fogolari, Federico

2017-11-21

Hydrophobic surfaces are known to adsorb and unfold proteins, a process that has been studied only for a few proteins. Here we address the interaction of β2-microglobulin, a paradigmatic protein for the study of amyloidogenesis, with hydrophobic surfaces. A system with 27 copies of the protein surrounded by a model cubic hydrophobic box is studied by implicit solvent molecular dynamics simulations. Most proteins adsorb on the walls of the box without major distortions in local geometry, whereas free molecules maintain proper structures and fluctuations as observed in explicit solvent molecular dynamics simulations. The major conclusions from the simulations are as follows: (i) the adopted implicit solvent model is adequate to describe protein dynamics and thermodynamics; (ii) adsorption occurs readily and is irreversible on the simulated timescale; (iii) the regions most involved in molecular encounters and stable interactions with the walls are the same as those that are important in protein-protein and protein-nanoparticle interactions; (iv) unfolding following adsorption occurs at regions found to be flexible by both experiments and simulations; (v) thermodynamic analysis suggests a very large contribution from van der Waals interactions, whereas unfavorable electrostatic interactions are not found to contribute much to adsorption energy. Surfaces with different degrees of hydrophobicity may occur in vivo. Our simulations show that adsorption is a fast and irreversible process which is accompanied by partial unfolding. The results and the thermodynamic analysis presented here are consistent with and rationalize previous experimental work.

Molecular Dynamics Simulations of Adhesion at Epoxy Interfaces

NASA Technical Reports Server (NTRS)

Frankland, Sarah-Jane V.; Clancy, Thomas C.; Hinkley, J. A.; Gates. T. S.

2008-01-01

The effect of moisture on adhesives used in aerospace applications can be modeled with chemically specific techniques such as molecular dynamics simulation. In the present study, the surface energy and work of adhesion are calculated for epoxy surfaces and interfaces, respectively, by using molecular dynamics simulation. Modifications are made to current theory to calculate the work of adhesion at the epoxy-epoxy interface with and without water. Quantitative agreement with experimental values is obtained for the surface energy and work of adhesion at the interface without water. The work of adhesion agrees qualitatively with the experimental values for the interface with water: the magnitude is reduced 15% with respect to the value for the interface without water. A variation of 26% in the magnitude is observed depending on the water configuration at a concentration of 1.6 wt%. The methods and modifications to the method that are employed to obtain these values are expected to be applicable for other epoxy adhesives to determine the effects of moisture uptake on their work of adhesion.

Molecular dynamics simulations of dense plasmas

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

Collins, L.A.; Kress, J.D.; Kwon, I.

1993-12-31

We have performed quantum molecular dynamics simulations of hot, dense plasmas of hydrogen over a range of temperatures(0.1-5eV) and densities(0.0625-5g/cc). We determine the forces quantum mechanically from density functional, extended Huckel, and tight binding techniques and move the nuclei according to the classical equations of motion. We determine pair-correlation functions, diffusion coefficients, and electrical conductivities. We find that many-body effects predominate in this regime. We begin to obtain agreement with the OCP and Thomas-Fermi models only at the higher temperatures and densities.

Visualizing functional motions of membrane transporters with molecular dynamics simulations.

PubMed

Shaikh, Saher A; Li, Jing; Enkavi, Giray; Wen, Po-Chao; Huang, Zhijian; Tajkhorshid, Emad

2013-01-29

Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins.

Visualizing Functional Motions of Membrane Transporters with Molecular Dynamics Simulations

PubMed Central

2013-01-01

Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins. PMID:23298176

Molecular dynamics simulations of human E3 ubiquitin ligase Parkin

PubMed Central

Qiu, Shi; Zhu, Shun; Xu, Shan; Han, Yanyan; Liu, Wen; Zuo, Ji

2017-01-01

Human E3 ubiquitin protein ligase parkin (Parkin) mediates mitophagy to maintain mitochondrial homeostasis. Parkin mutations are common genetic causes of early onset familial Parkinson's disease. The molecular mechanism of Parkin activation has been widely studied with emerging evidence suggesting an essential role of the phosphorylated (phospho)-ubiquitin interaction. However, the underlying mechanism of the phospho-ubiquitin interaction remains elusive. In the present study, replica exchange molecular dynamics simulations were performed to examine the conformational dynamics of Parkin in monomer and phospho-ubiquitin-bound states. In the Parkin monomer state, high structural flexibilities were observed in the majority of regions of Parkin particularly in the loop domain between the ubiquitin-like (UBL) and really interesting new gene (RING)0 domain. Binding of phospho-ubiquitin stabilizes the RING1/RING in between RING interface but destabilizes the RING1-UBL interface. Furthermore, using steered molecular dynamics simulations of Parkin mutations, it was demonstrated that salt bridge interactions contribute significantly to the interdomain interactions between the RING1 and UBL domain. Taken together, the results of the present study revealed the conformational dynamics of human full-length Parkin in monomer and phospho-ubiquitin-bound states, providing insights into designing potential therapeutics against Parkinson's disease. PMID:28765939

Molecular dynamics simulations of human E3 ubiquitin ligase Parkin.

PubMed

Qiu, Shi; Zhu, Shun; Xu, Shan; Han, Yanyan; Liu, Wen; Zuo, Ji

2017-10-01

Human E3 ubiquitin protein ligase parkin (Parkin) mediates mitophagy to maintain mitochondrial homeostasis. Parkin mutations are common genetic causes of early onset familial Parkinson's disease. The molecular mechanism of Parkin activation has been widely studied with emerging evidence suggesting an essential role of the phosphorylated (phospho)‑ubiquitin interaction. However, the underlying mecha-nism of the phospho‑ubiquitin interaction remains elusive. In the present study, replica exchange molecular dynamics simulations were performed to examine the conformational dynamics of Parkin in monomer and phospho‑ubiquitin‑bound states. In the Parkin monomer state, high structural flexi-bilities were observed in the majority of regions of Parkin particularly in the loop domain between the ubiquitin‑like (UBL) and really interesting new gene (RING)0 domain. Binding of phospho‑ubiquitin stabilizes the RING1/RING in between RING interface but destabilizes the RING1‑UBL interface. Furthermore, using steered molecular dynamics simulations of Parkin mutations, it was demonstrated that salt bridge interactions contribute significantly to the interdomain interactions between the RING1 and UBL domain. Taken together, the results of the present study revealed the conformational dynamics of human full‑length Parkin in monomer and phospho‑ubiquitin‑bound states, providing insights into designing potential therapeutics against Parkinson's disease.

The molecular dynamics simulation of ion-induced ripple growth

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

Suele, P.; Heinig, K.-H.

The wavelength-dependence of ion-sputtering induced growth of repetitive nanostructures, such as ripples has been studied by molecular dynamics (MD) simulations in Si. The early stage of the ion erosion driven development of ripples has been simulated on prepatterned Si stripes with a wavy surface. The time evolution of the height function and amplitude of the sinusoidal surface profile has been followed by simulated ion-sputtering. According to Bradley-Harper (BH) theory, we expect correlation between the wavelength of ripples and the stability of them. However, we find that in the small ripple wavelength ({lambda}) regime BH theory fails to reproduce the resultsmore » obtained by molecular dynamics. We find that at short wavelengths ({lambda}<35 nm) the adatom yield drops hence no surface diffusion takes place which is sufficient for ripple growth. The MD simulations predict that the growth of ripples with {lambda}>35 nm is stabilized in accordance with the available experimental results. According to the simulations, few hundreds of ion impacts in {lambda} long and few nanometers wide Si ripples are sufficient for reaching saturation in surface growth for for {lambda}>35 nm ripples. In another words, ripples in the long wavelength limit seems to be stable against ion-sputtering. A qualitative comparison of our simulation results with recent experimental data on nanopatterning under irradiation is attempted.« less

Molecular dynamics modeling and simulation of void growth in two dimensions

NASA Astrophysics Data System (ADS)

Chang, H.-J.; Segurado, J.; Rodríguez de la Fuente, O.; Pabón, B. M.; LLorca, J.

2013-10-01

The mechanisms of growth of a circular void by plastic deformation were studied by means of molecular dynamics in two dimensions (2D). While previous molecular dynamics (MD) simulations in three dimensions (3D) have been limited to small voids (up to ≈10 nm in radius), this strategy allows us to study the behavior of voids of up to 100 nm in radius. MD simulations showed that plastic deformation was triggered by the nucleation of dislocations at the atomic steps of the void surface in the whole range of void sizes studied. The yield stress, defined as stress necessary to nucleate stable dislocations, decreased with temperature, but the void growth rate was not very sensitive to this parameter. Simulations under uniaxial tension, uniaxial deformation and biaxial deformation showed that the void growth rate increased very rapidly with multiaxiality but it did not depend on the initial void radius. These results were compared with previous 3D MD and 2D dislocation dynamics simulations to establish a map of mechanisms and size effects for plastic void growth in crystalline solids.

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.

Stabilities and Dynamics of Protein Folding Nuclei by Molecular Dynamics Simulation

NASA Astrophysics Data System (ADS)

Song, Yong-Shun; Zhou, Xin; Zheng, Wei-Mou; Wang, Yan-Ting

2017-07-01

To understand how the stabilities of key nuclei fragments affect protein folding dynamics, we simulate by molecular dynamics (MD) simulation in aqueous solution four fragments cut out of a protein G, including one α-helix (seqB: KVFKQYAN), two β-turns (seqA: LNGKTLKG and seqC: YDDATKTF), and one β-strand (seqD: DGEWTYDD). The Markov State Model clustering method combined with the coarse-grained conformation letters method are employed to analyze the data sampled from 2-μs equilibrium MD simulation trajectories. We find that seqA and seqB have more stable structures than their native structures which become metastable when cut out of the protein structure. As expected, seqD alone is flexible and does not have a stable structure. Throughout our simulations, the native structure of seqC is stable but cannot be reached if starting from a structure other than the native one, implying a funnel-shape free energy landscape of seqC in aqueous solution. All the above results suggest that different nuclei have different formation dynamics during protein folding, which may have a major contribution to the hierarchy of protein folding dynamics. Supported by the National Basic Research Program of China under Grant No. 2013CB932804, the National Natural Science Foundation of China under Grant No. 11421063, and the CAS Biophysics Interdisciplinary Innovation Team Project

Fiber lubrication: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Liu, Hongyi

Molecular and mesoscopic level description of friction and lubrication remains a challenge because of difficulties in the phenomenological understanding of to the behaviors of solid-liquid interfaces during sliding. Fortunately, there is the computational simulation approach opens an opportunity to predict and analyze interfacial phenomena, which were studied with molecular dynamics (MD) and mesoscopic dynamics (MesoDyn) simulations. Polypropylene (PP) and cellulose are two of most common polymers in textile fibers. Confined amorphous surface layers of PP and cellulose were built successfully with xenon crystals which were used to compact the polymers. The physical and surface properties of the PP and cellulose surface layers were investigated by MD simulations, including the density, cohesive energy, volumetric thermal expansion, and contact angle with water. The topology method was employed to predict the properties of poly(alkylene glycol) (PAG) diblock copolymers and Pluronic triblock copolymers used as lubricants on surfaces. Density, zero shear viscosity, shear module, cohesive energy and solubility parameter were predicted with each block copolymer. Molecular dynamics simulations were used to study the interaction energy per unit contact area of block copolymer melts with PP and cellulose surfaces. The interaction energy is defined as the ratio of interfacial interaction energy to the contact area. Both poly(proplene oxide) (PPO) and poly(ethylene oxide) (PEO) segments provided a lipophilic character to both PP and cellulose surfaces. The PPO/PEO ratio and the molecular weight were found to impact the interaction energy on both PP and cellulose surfaces. In aqueous solutions, the interaction energy is complicated due to the presence of water and the cross interactions between the multiple molecular components. The polymer-water-surface (PWS) calculation method was proposed to calculate such complex systems. In a contrast with a vacuum condition, the presence

Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics: strength in unity.

PubMed

Papaleo, Elena

2015-01-01

In the last years, we have been observing remarkable improvements in the field of protein dynamics. Indeed, we can now study protein dynamics in atomistic details over several timescales with a rich portfolio of experimental and computational techniques. On one side, this provides us with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome their own limitations. Moreover, now that we have the means to study protein dynamics in great details, we need new tools to understand the information embedded in the protein ensembles and in their dynamic signature. With this aim in mind, we should enrich the current tools for analysis of biomolecular simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations.

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.

Wetting of crystalline polymer surfaces: A molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Fan, Cun Feng; Caǧin, Tahir

1995-11-01

Molecular dynamics has been used to study the wetting of model polymer surfaces, the crystal surfaces of polyethylene (PE), poly(tetrafluoroethylene) (PTFE), and poly(ethylene terephthalate) (PET) by water and methylene iodide. In the simulation a liquid droplet is placed on a model surface and constant temperature, rigid body molecular dynamics is carried out while the model surface is kept fixed. A generally defined microscopic contact angle between a liquid droplet and a solid surface is quantitatively calculated from the volume of the droplet and the interfacial area between the droplet and the surface. The simulation results agree with the trend in experimental data for both water and methylene iodide. The shape of the droplets on the surface is analyzed and no obvious anisotropy of the droplets is seen in the surface plane, even though the crystal surfaces are highly oriented. The surface free energies of the model polymer surfaces are estimated from their contact angles with the two different liquid droplets.

A high performance system for molecular dynamics simulation of biomolecules using a special-purpose computer.

PubMed

Komeiji, Y; Yokoyama, H; Uebayasi, M; Taiji, M; Fukushige, T; Sugimoto, D; Takata, R; Shimizu, A; Itsukashi, K

1996-01-01

GRAPE (GRavity PipE) processors are special purpose computers for simulation of classical particles. The performance of MD-GRAPE, one of the GRAPEs developed for molecular dynamics, was investigated. The effective speed of MD-GRAPE was equivalent to approximately 6 Gflops. The precision of MD-GRAPE was good judging from the acceptable fluctuation of the total energy. Then a software named PEACH (Program for Energetic Analysis of bioCHemical molecules) was developed for molecular dynamics of biomolecules in combination with MD-GRAPE. Molecular dynamics simulation was performed for several protein-solvent systems with different sizes. Simulation of the largest system investigated (27,000 atoms) took only 5 sec/step. Thus, the PEACH-GRAPE system is expected to be useful in accurate and reliable simulation of large biomolecules.

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

Structure of a tethered polymer under flow using molecular dynamics and hybrid molecular-continuum simulations

NASA Astrophysics Data System (ADS)

Delgado-Buscalioni, Rafael; Coveney, Peter V.

2006-03-01

We analyse the structure of a single polymer tethered to a solid surface undergoing a Couette flow. We study the problem using molecular dynamics (MD) and hybrid MD-continuum simulations, wherein the polymer and the surrounding solvent are treated via standard MD, and the solvent flow farther away from the polymer is solved by continuum fluid dynamics (CFD). The polymer represents a freely jointed chain (FJC) and is modelled by Lennard-Jones (LJ) beads interacting through the FENE potential. The solvent (modelled as a LJ fluid) and a weakly attractive wall are treated at the molecular level. At large shear rates the polymer becomes more elongated than predicted by existing theoretical scaling laws. Also, along the normal-to-wall direction the structure observed for the FJC is, surprisingly, very similar to that predicted for a semiflexible chain. Comparison with previous Brownian dynamics simulations (which exclude both solvent and wall potential) indicates that these effects are due to the polymer-solvent and polymer-wall interactions. The hybrid simulations are in perfect agreement with the MD simulations, showing no trace of finite size effects. Importantly, the extra cost required to couple the MD and CFD domains is negligible.

Molecular Dynamics Simulation of Carbon Nanotube Based Gears

NASA Technical Reports Server (NTRS)

Han, Jie; Globus, Al; Jaffe, Richard; Deardorff, Glenn; Chancellor, Marisa K. (Technical Monitor)

1996-01-01

We used molecular dynamics to investigate the properties and design space of molecular gears fashioned from carbon nanotubes with teeth added via a benzyne reaction known to occur with C60. A modified, parallelized version of Brenner's potential was used to model interatomic forces within each molecule. A Leonard-Jones 6-12 potential was used for forces between molecules. One gear was powered by forcing the atoms near the end of the buckytube to rotate, and a second gear was allowed.to rotate by keeping the atoms near the end of its buckytube on a cylinder. The meshing aromatic gear teeth transfer angular momentum from the powered gear to the driven gear. A number of gear and gear/shaft configurations were simulated. Cases in vacuum and with an inert atmosphere were examined. In an extension to molecular dynamics technology, some simulations used a thermostat on the atmosphere while the hydrocarbon gear's temperature was allowed to fluctuate. This models cooling the gears with an atmosphere. Results suggest that these gears can operate at up to 50-100 gigahertz in a vacuum or inert atmosphere at room temperature. The failure mode involves tooth slip, not bond breaking, so failed gears can be returned to operation by lowering temperature and/or rotation rate. Videos and atomic trajectory files in xyz format are presented.

Dynamics and unfolding pathway of chimeric azurin variants: insights from molecular dynamics simulation.

PubMed

Evoli, Stefania; Guzzi, Rita; Rizzuti, Bruno

2013-10-01

The spectroscopic, thermal, and functional properties of blue copper proteins can be modulated by mutations in the metal binding loop. Molecular dynamics simulation was used to compare the conformational properties of azurin and two chimeric variants, which were obtained by inserting into the azurin scaffold the copper binding loop of amicyanin and plastocyanin, respectively. Simulations at room temperature show that the proteins retain their overall structure and exhibit concerted motions among specific inner regions, as revealed by principal component analysis. Molecular dynamics at high temperature indicates that the first events in the unfolding pathway are structurally similar in the three proteins and unfolding starts from the region of the α-helix that is far from the metal binding loop. The results provide details of the denaturation process that are consistent with experimental data and in close agreement with other computational approaches, suggesting a distinct mechanism of unfolding of azurin and its chimeric variants. Moreover, differences observed in the dynamics of specific regions in the three proteins correlate with their thermal behavior, contributing to the determination of the basic factors that influence the stability.

Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation.

PubMed

Dalby, Andrew; Shamsir, Mohd Shahir

2015-01-01

Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation.

Spotting the difference in molecular dynamics simulations of biomolecules

NASA Astrophysics Data System (ADS)

Sakuraba, Shun; Kono, Hidetoshi

2016-08-01

Comparing two trajectories from molecular simulations conducted under different conditions is not a trivial task. In this study, we apply a method called Linear Discriminant Analysis with ITERative procedure (LDA-ITER) to compare two molecular simulation results by finding the appropriate projection vectors. Because LDA-ITER attempts to determine a projection such that the projections of the two trajectories do not overlap, the comparison does not suffer from a strong anisotropy, which is an issue in protein dynamics. LDA-ITER is applied to two test cases: the T4 lysozyme protein simulation with or without a point mutation and the allosteric protein PDZ2 domain of hPTP1E with or without a ligand. The projection determined by the method agrees with the experimental data and previous simulations. The proposed procedure, which complements existing methods, is a versatile analytical method that is specialized to find the "difference" between two trajectories.

Revealing Atomic-Level Mechanisms of Protein Allostery with Molecular Dynamics Simulations.

PubMed

Hertig, Samuel; Latorraca, Naomi R; Dror, Ron O

2016-06-01

Molecular dynamics (MD) simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein's constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery-the fact that the two sites involved influence one another in a symmetrical manner-can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest.

Molecular Dynamics, Monte Carlo Simulations, and Langevin Dynamics: A Computational Review

PubMed Central

Paquet, Eric; Viktor, Herna L.

2015-01-01

Macromolecular structures, such as neuraminidases, hemagglutinins, and monoclonal antibodies, are not rigid entities. Rather, they are characterised by their flexibility, which is the result of the interaction and collective motion of their constituent atoms. This conformational diversity has a significant impact on their physicochemical and biological properties. Among these are their structural stability, the transport of ions through the M2 channel, drug resistance, macromolecular docking, binding energy, and rational epitope design. To assess these properties and to calculate the associated thermodynamical observables, the conformational space must be efficiently sampled and the dynamic of the constituent atoms must be simulated. This paper presents algorithms and techniques that address the abovementioned issues. To this end, a computational review of molecular dynamics, Monte Carlo simulations, Langevin dynamics, and free energy calculation is presented. The exposition is made from first principles to promote a better understanding of the potentialities, limitations, applications, and interrelations of these computational methods. PMID:25785262

Dielectric Properties of Poly(ethylene oxide) from Molecular Dynamics Simulations

NASA Technical Reports Server (NTRS)

Smith, Grant D.

1994-01-01

The order, conformations and dynamics of poly(oxyethylene) (POE) melts have been investigated through molecular dynamics simulations. The potential energy functions were determined from detailed ab initio electronic structure calculations of the conformational energies of the model molecules 1,2-dimethoxyethane (DME) and diethylether. The x-ray structure factor for POE from simulation will be compared to experiment. In terms of conformation, simulations reveal that chains are extended in the melt relative to isolated chains due to the presence of strong intermolecular O...H interactions, which occur at the expense of intramolecular O...H interactions. Conformational dynamics about the C-C bond were found to be significantly faster than in polymethylene, while conformational dynamics about the C-O bond even faster than the C-C dynamics. The faster local dynamics in POE relative to polymethylene is consistent with C-13 NMR spin-lattice relaxation experiments. Conformational transitions showed significant second-neighbor correlation, as was found for polymethylene. This correlation of transitions with C-C neighbors was found to be reduced relative to C-O neighbors. Dielectric relaxation from simulation will also be compared with experiment.

Recent applications of boxed molecular dynamics: a simple multiscale technique for atomistic simulations.

PubMed

Booth, Jonathan; Vazquez, Saulo; Martinez-Nunez, Emilio; Marks, Alison; Rodgers, Jeff; Glowacki, David R; Shalashilin, Dmitrii V

2014-08-06

In this paper, we briefly review the boxed molecular dynamics (BXD) method which allows analysis of thermodynamics and kinetics in complicated molecular systems. BXD is a multiscale technique, in which thermodynamics and long-time dynamics are recovered from a set of short-time simulations. In this paper, we review previous applications of BXD to peptide cyclization, solution phase organic reaction dynamics and desorption of ions from self-assembled monolayers (SAMs). We also report preliminary results of simulations of diamond etching mechanisms and protein unfolding in atomic force microscopy experiments. The latter demonstrate a correlation between the protein's structural motifs and its potential of mean force. Simulations of these processes by standard molecular dynamics (MD) is typically not possible, because the experimental time scales are very long. However, BXD yields well-converged and physically meaningful results. Compared with other methods of accelerated MD, our BXD approach is very simple; it is easy to implement, and it provides an integrated approach for simultaneously obtaining both thermodynamics and kinetics. It also provides a strategy for obtaining statistically meaningful dynamical results in regions of configuration space that standard MD approaches would visit only very rarely.

Non-equilibrium dynamics in disordered materials: Ab initio molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Ohmura, Satoshi; Nagaya, Kiyonobu; Shimojo, Fuyuki; Yao, Makoto

2015-08-01

The dynamic properties of liquid B2O3 under pressure and highly-charged bromophenol molecule are studied by using molecular dynamics (MD) simulations based on density functional theory (DFT). Diffusion properties of covalent liquids under high pressure are very interesting in the sense that they show unexpected pressure dependence. It is found from our simulation that the magnitude relation of diffusion coefficients for boron and oxygen in liquid B2O3 shows the anomalous pressure dependence. The simulation clarified the microscopic origin of the anomalous diffusion properties. Our simulation also reveals the dissociation mechanism in the coulomb explosion of the highly-charged bromophenol molecule. When the charge state n is 6, hydrogen atom in the hydroxyl group dissociates at times shorter than 20 fs while all hydrogen atoms dissociate when n is 8. After the hydrogen dissociation, the carbon ring breaks at about 100 fs. There is also a difference on the mechanism of the ring breaking depending on charge states, in which the ring breaks with expanding (n = 6) or shrink (n = 8).

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms.

PubMed

Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

2016-07-01

This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms☆

PubMed Central

Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

2016-01-01

This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins. Guest Editors: J.C. Gumbart and Sergei Noskov. PMID:26766517

Molecular dynamics simulation of polyacrylamides in potassium montmorillonite clay hydrates

NASA Astrophysics Data System (ADS)

Zhang, Junfang; Rivero, Mayela; Choi, S. K.

2007-02-01

We present molecular dynamics simulation results for polyacrylamide in potassium montmorillonite clay-aqueous systems. Interlayer molecular structure and dynamics properties are investigated. The number density profile, radial distribution function, root-mean-square deviation (RMSD), mean-square displacement (MSD) and diffusion coefficient are reported. The calculations are conducted in constant NVT ensembles, at T = 300 K and with layer spacing of 40 Å. Our simulation results showed that polyacrylamides had little impact on the structure of interlayer water. Density profiles and radial distribution function indicated that hydration shells were formed. In the presence of polyacrylamides more potassium counterions move close to the clay surface while water molecules move away, indicating that potassium counterions are hydrated to a lesser extent than the system in which no polyacrylamides were added. The diffusion coefficients for potassium and water decreased when polyacrylamides were added.

Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation.

PubMed Central

Dalby, Andrew; Shamsir, Mohd Shahir

2015-01-01

Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation. PMID:26539292

Ab initio molecular dynamics simulation of LiBr association in water

NASA Astrophysics Data System (ADS)

Izvekov, Sergei; Philpott, Michael R.

2000-12-01

A computationally economical scheme which unifies the density functional description of an ionic solute and the classical description of a solvent was developed. The density functional part of the scheme comprises Car-Parrinello and related formalisms. The substantial saving in the computer time is achieved by performing the ab initio molecular dynamics of the solute electronic structure in a relatively small basis set constructed from lowest energy Kohn-Sham orbitals calculated for a single anion in vacuum, instead of using plane wave basis. The methodology permits simulation of an ionic solution for longer time scales while keeping accuracy in the prediction of the solute electronic structure. As an example the association of the Li+-Br- ion-pair system in water is studied. The results of the combined molecular dynamics simulation are compared with that obtained from the classical simulation with ion-ion interaction described by the pair potential of Born-Huggins-Mayer type. The comparison reveals an important role played by the polarization of the Br- ion in the dynamics of ion pair association.

Allosteric dynamics of SAMHD1 studied by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Patra, K. K.; Bhattacharya, A.; Bhattacharya, S.

2016-10-01

SAMHD1 is a human cellular enzyme that blocks HIV-1 infection in myeloid cells and non-cycling CD4+T cells. The enzyme is an allosterically regulated triphosphohydrolase that modulates the level of cellular dNTP. The virus restriction is attributed to the lowering of the pool of dNTP in the cell to a point where reverse-transcription is impaired. Mutations in SAMHD1 are also implicated in Aicardi-Goutieres syndrome. A mechanistic understanding of the allosteric activation of the enzyme is still elusive. We have performed molecular dynamics simulations to examine the allosteric site dynamics of the protein and to examine the connection between the stability of the tetrameric complex and the Allosite occupancy.

Study of the dynamics of poly(ethylene oxide) by combining molecular dynamic simulations and neutron scattering experiments

NASA Astrophysics Data System (ADS)

Brodeck, M.; Alvarez, F.; Arbe, A.; Juranyi, F.; Unruh, T.; Holderer, O.; Colmenero, J.; Richter, D.

2009-03-01

We performed quasielastic neutron scattering experiments and atomistic molecular dynamics simulations on a poly(ethylene oxide) (PEO) homopolymer system above the melting point. The excellent agreement found between both sets of data, together with a successful comparison with literature diffraction results, validates the condensed-phase optimized molecular potentials for atomistic simulation studies (COMPASS) force field used to produce our dynamic runs and gives support to their further analysis. This provided direct information on magnitudes which are not accessible from experiments such as the radial probability distribution functions of specific atoms at different times and their moments. The results of our simulations on the H-motions and different experiments indicate that in the high-temperature range investigated the dynamics is Rouse-like for Q-values below ≈0.6 Å-1. We then addressed the single chain dynamic structure factor with the simulations. A mode analysis, not possible directly experimentally, reveals the limits of applicability of the Rouse model to PEO. We discuss the possible origins for the observed deviations.

Study of the dynamics of poly(ethylene oxide) by combining molecular dynamic simulations and neutron scattering experiments.

PubMed

Brodeck, M; Alvarez, F; Arbe, A; Juranyi, F; Unruh, T; Holderer, O; Colmenero, J; Richter, D

2009-03-07

We performed quasielastic neutron scattering experiments and atomistic molecular dynamics simulations on a poly(ethylene oxide) (PEO) homopolymer system above the melting point. The excellent agreement found between both sets of data, together with a successful comparison with literature diffraction results, validates the condensed-phase optimized molecular potentials for atomistic simulation studies (COMPASS) force field used to produce our dynamic runs and gives support to their further analysis. This provided direct information on magnitudes which are not accessible from experiments such as the radial probability distribution functions of specific atoms at different times and their moments. The results of our simulations on the H-motions and different experiments indicate that in the high-temperature range investigated the dynamics is Rouse-like for Q-values below approximately 0.6 A(-1). We then addressed the single chain dynamic structure factor with the simulations. A mode analysis, not possible directly experimentally, reveals the limits of applicability of the Rouse model to PEO. We discuss the possible origins for the observed deviations.

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.

Molecular dynamics computer simulation of permeation in solids

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

Pohl, P.I.; Heffelfinger, G.S.; Fisler, D.K.

1997-12-31

In this work the authors simulate permeation of gases and cations in solid models using molecular mechanics and a dual control volume grand canonical molecular dynamics technique. The molecular sieving nature of microporous zeolites are discussed and compared with that for amorphous silica made by sol-gel methods. One mesoporous and one microporous membrane model are tested with Lennard-Jones gases corresponding to He, H{sub 2}, Ar and CH{sub 4}. The mesoporous membrane model clearly follows a Knudsen diffusion mechanism, while the microporous model having a hard-sphere cutoff pore diameter of {approximately}3.4 {angstrom} demonstrates molecular sieving of the methane ({sigma} = 3.8more » {angstrom}) but anomalous behavior for Ar ({sigma} = 3.4 {angstrom}). Preliminary results of Ca{sup +} diffusion in calcite and He/H{sub 2} diffusion in polyisobutylene are also presented.« less

Molecular dynamics simulations of oxide memory resistors (memristors).

PubMed

Savel'ev, S E; Alexandrov, A S; Bratkovsky, A M; Williams, R Stanley

2011-06-24

Reversible bipolar nanoswitches that can be set and read electronically in a solid-state two-terminal device are very promising for applications. We have performed molecular dynamics simulations that mimic systems with oxygen vacancies interacting via realistic potentials and driven by an external bias voltage. The competing short- and long-range interactions among charged mobile vacancies lead to density fluctuations and short-range ordering, while illustrating some aspects of observed experimental behavior, such as memristor polarity inversion. The simulations show that the 'localized conductive filaments' and 'uniform push/pull' models for memristive switching are actually two extremes of the one stochastic mechanism.

Using collective variables to drive molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Fiorin, Giacomo; Klein, Michael L.; Hénin, Jérôme

2013-12-01

A software framework is introduced that facilitates the application of biasing algorithms to collective variables of the type commonly employed to drive massively parallel molecular dynamics (MD) simulations. The modular framework that is presented enables one to combine existing collective variables into new ones, and combine any chosen collective variable with available biasing methods. The latter include the classic time-dependent biases referred to as steered MD and targeted MD, the temperature-accelerated MD algorithm, as well as the adaptive free-energy biases called metadynamics and adaptive biasing force. The present modular software is extensible, and portable between commonly used MD simulation engines.

Multiscale simulations of patchy particle systems combining Molecular Dynamics, Path Sampling and Green's Function Reaction Dynamics

NASA Astrophysics Data System (ADS)

Bolhuis, Peter

Important reaction-diffusion processes, such as biochemical networks in living cells, or self-assembling soft matter, span many orders in length and time scales. In these systems, the reactants' spatial dynamics at mesoscopic length and time scales of microns and seconds is coupled to the reactions between the molecules at microscopic length and time scales of nanometers and milliseconds. This wide range of length and time scales makes these systems notoriously difficult to simulate. While mean-field rate equations cannot describe such processes, the mesoscopic Green's Function Reaction Dynamics (GFRD) method enables efficient simulation at the particle level provided the microscopic dynamics can be integrated out. Yet, many processes exhibit non-trivial microscopic dynamics that can qualitatively change the macroscopic behavior, calling for an atomistic, microscopic description. The recently developed multiscale Molecular Dynamics Green's Function Reaction Dynamics (MD-GFRD) approach combines GFRD for simulating the system at the mesocopic scale where particles are far apart, with microscopic Molecular (or Brownian) Dynamics, for simulating the system at the microscopic scale where reactants are in close proximity. The association and dissociation of particles are treated with rare event path sampling techniques. I will illustrate the efficiency of this method for patchy particle systems. Replacing the microscopic regime with a Markov State Model avoids the microscopic regime completely. The MSM is then pre-computed using advanced path-sampling techniques such as multistate transition interface sampling. I illustrate this approach on patchy particle systems that show multiple modes of binding. MD-GFRD is generic, and can be used to efficiently simulate reaction-diffusion systems at the particle level, including the orientational dynamics, opening up the possibility for large-scale simulations of e.g. protein signaling networks.

Molecular dynamics simulations of a K+ channel blocker: Tc1 toxin from Tityus cambridgei.

PubMed

Grottesi, Alessandro; Sansom, Mark S P

2003-01-30

Toxins that block voltage-gated potassium (Kv) channels provide a possible template for improved homology models of the Kv pore. In assessing the interactions of Kv channels and their toxins it is important to determine the dynamic flexibility of the toxins. Multiple 10 ns duration molecular dynamics simulations combined with essential dynamics analysis have been used to explore the flexibility of four different Kv channel-blocking toxins. Three toxins (Tc1, AgTx and ChTx) share a common fold. They also share a common pattern of conformational dynamics, as revealed by essential dynamics analysis of the simulation results. This suggests that some aspects of dynamic behaviour are conserved across a single protein fold class. In each of these three toxins, the residue exhibiting minimum flexibility corresponds to a conserved lysine residue that is suggested to interact with the filter domain of the channel. Thus, comparative simulations reveal functionally important conservation of molecular dynamics as well as protein fold across a family of related toxins.

Self Diffusion in Nano Filled Polymer Melts: a Molecular Dynamics Simulation Study

NASA Astrophysics Data System (ADS)

Desai, Tapan; Keblinski, Pawel

2003-03-01

SELF DIFFUSION IN NANO FILLED POLYMER MELTS: A MOLECULAR DYNAMICS SIMULATION STUDY* T. G. Desai,P. Keblinski, Material Science and Engineering Department, Rensselaer Polytechnic Institute, Troy, NY. Using molecular dynamics simulations, we studied the dynamics of the polymeric systems containing immobile and analytically smooth spherical nanoparticles. Each chain consisted of N monomers connected by an anharmonic springs described by the finite extendible nonlinear elastic, FENE potential. The system comprises of 3nanoparticles and the rest by freely rotating but not overlapping chains. The longest chain studied has a Radius of gyration equal to particle size radius and comparable to inter-particle distance. There is no effect on the structural characteristics such as Radius of gyration or end to end distance due to the nanoparticles. Diffusion of polymeric chains is not affected by the presence of either attractive or repulsive nanoparticles. In all cases Rouse dynamics is observed for short chains with a crossover to reptation dynamics for longer chains.

Microsecond Molecular Dynamics Simulations of Lipid Mixing

PubMed Central

2015-01-01

Molecular dynamics (MD) simulations of membranes are often hindered by the slow lateral diffusion of lipids and the limited time scale of MD. In order to study the dynamics of mixing and characterize the lateral distribution of lipids in converged mixtures, we report microsecond-long all-atom MD simulations performed on the special-purpose machine Anton. Two types of mixed bilayers, POPE:POPG (3:1) and POPC:cholesterol (2:1), as well as a pure POPC bilayer, were each simulated for up to 2 μs. These simulations show that POPE:POPG and POPC:cholesterol are each fully miscible at the simulated conditions, with the final states of the mixed bilayers similar to a random mixture. By simulating three POPE:POPG bilayers at different NaCl concentrations (0, 0.15, and 1 M), we also examined the effect of salt concentration on lipid mixing. While an increase in NaCl concentration is shown to affect the area per lipid, tail order, and lipid lateral diffusion, the final states of mixing remain unaltered, which is explained by the largely uniform increase in Na+ ions around POPE and POPG. Direct measurement of water permeation reveals that the POPE:POPG bilayer with 1 M NaCl has reduced water permeability compared with those at zero or low salt concentration. Our calculations provide a benchmark to estimate the convergence time scale of all-atom MD simulations of lipid mixing. Additionally, equilibrated structures of POPE:POPG and POPC:cholesterol, which are frequently used to mimic bacterial and mammalian membranes, respectively, can be used as starting points of simulations involving these membranes. PMID:25237736

Molecular dynamics simulations through GPU video games technologies

PubMed Central

Loukatou, Styliani; Papageorgiou, Louis; Fakourelis, Paraskevas; Filntisi, Arianna; Polychronidou, Eleftheria; Bassis, Ioannis; Megalooikonomou, Vasileios; Makałowski, Wojciech; Vlachakis, Dimitrios; Kossida, Sophia

2016-01-01

Bioinformatics is the scientific field that focuses on the application of computer technology to the management of biological information. Over the years, bioinformatics applications have been used to store, process and integrate biological and genetic information, using a wide range of methodologies. One of the most de novo techniques used to understand the physical movements of atoms and molecules is molecular dynamics (MD). MD is an in silico method to simulate the physical motions of atoms and molecules under certain conditions. This has become a state strategic technique and now plays a key role in many areas of exact sciences, such as chemistry, biology, physics and medicine. Due to their complexity, MD calculations could require enormous amounts of computer memory and time and therefore their execution has been a big problem. Despite the huge computational cost, molecular dynamics have been implemented using traditional computers with a central memory unit (CPU). A graphics processing unit (GPU) computing technology was first designed with the goal to improve video games, by rapidly creating and displaying images in a frame buffer such as screens. The hybrid GPU-CPU implementation, combined with parallel computing is a novel technology to perform a wide range of calculations. GPUs have been proposed and used to accelerate many scientific computations including MD simulations. Herein, we describe the new methodologies developed initially as video games and how they are now applied in MD simulations. PMID:27525251

Autoinhibitory mechanisms of ERG studied by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Lu, Yan; Salsbury, Freddie R.

2015-01-01

ERG, an ETS-family transcription factor, acts as a regulator of differentiation of early hematopoietic cells. It contains an autoinhibitory domain, which negatively regulates DNA-binding. The mechanism of autoinhibitory is still illusive. To understand the mechanism, we study the dynamical properties of ERG protein by molecular dynamics simulations. These simulations suggest that DNA binding autoinhibition associates with the internal dynamics of ERG. Specifically, we find that (1), The N-C terminal correlation in the inhibited ERG is larger than that in uninhibited ERG that contributes to the autoinhibition of DNA-binding. (2), DNA-binding changes the property of the N-C terminal correlation from being anti-correlated to correlated, that is, changing the relative direction of the correlated motions and (3), For the Ets-domain specifically, the inhibited and uninhibited forms exhibit essentially the same dynamics, but the binding of the DNA decreases the fluctuation of the Ets-domain. We also find from PCA analysis that the three systems, even with quite different dynamics, do have highly similar free energy surfaces, indicating that they share similar conformations.

MDGRAPE-4: a special-purpose computer system for molecular dynamics simulations.

PubMed

Ohmura, Itta; Morimoto, Gentaro; Ohno, Yousuke; Hasegawa, Aki; Taiji, Makoto

2014-08-06

We are developing the MDGRAPE-4, a special-purpose computer system for molecular dynamics (MD) simulations. MDGRAPE-4 is designed to achieve strong scalability for protein MD simulations through the integration of general-purpose cores, dedicated pipelines, memory banks and network interfaces (NIFs) to create a system on chip (SoC). Each SoC has 64 dedicated pipelines that are used for non-bonded force calculations and run at 0.8 GHz. Additionally, it has 65 Tensilica Xtensa LX cores with single-precision floating-point units that are used for other calculations and run at 0.6 GHz. At peak performance levels, each SoC can evaluate 51.2 G interactions per second. It also has 1.8 MB of embedded shared memory banks and six network units with a peak bandwidth of 7.2 GB s(-1) for the three-dimensional torus network. The system consists of 512 (8×8×8) SoCs in total, which are mounted on 64 node modules with eight SoCs. The optical transmitters/receivers are used for internode communication. The expected maximum power consumption is 50 kW. While MDGRAPE-4 software has still been improved, we plan to run MD simulations on MDGRAPE-4 in 2014. The MDGRAPE-4 system will enable long-time molecular dynamics simulations of small systems. It is also useful for multiscale molecular simulations where the particle simulation parts often become bottlenecks.

MDGRAPE-4: a special-purpose computer system for molecular dynamics simulations

PubMed Central

Ohmura, Itta; Morimoto, Gentaro; Ohno, Yousuke; Hasegawa, Aki; Taiji, Makoto

2014-01-01

We are developing the MDGRAPE-4, a special-purpose computer system for molecular dynamics (MD) simulations. MDGRAPE-4 is designed to achieve strong scalability for protein MD simulations through the integration of general-purpose cores, dedicated pipelines, memory banks and network interfaces (NIFs) to create a system on chip (SoC). Each SoC has 64 dedicated pipelines that are used for non-bonded force calculations and run at 0.8 GHz. Additionally, it has 65 Tensilica Xtensa LX cores with single-precision floating-point units that are used for other calculations and run at 0.6 GHz. At peak performance levels, each SoC can evaluate 51.2 G interactions per second. It also has 1.8 MB of embedded shared memory banks and six network units with a peak bandwidth of 7.2 GB s−1 for the three-dimensional torus network. The system consists of 512 (8×8×8) SoCs in total, which are mounted on 64 node modules with eight SoCs. The optical transmitters/receivers are used for internode communication. The expected maximum power consumption is 50 kW. While MDGRAPE-4 software has still been improved, we plan to run MD simulations on MDGRAPE-4 in 2014. The MDGRAPE-4 system will enable long-time molecular dynamics simulations of small systems. It is also useful for multiscale molecular simulations where the particle simulation parts often become bottlenecks. PMID:24982255

Shock waves simulated using the dual domain material point method combined with molecular dynamics

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

Zhang, Duan Z.; Dhakal, Tilak Raj

Here in this work we combine the dual domain material point method with molecular dynamics in an attempt to create a multiscale numerical method to simulate materials undergoing large deformations with high strain rates. In these types of problems, the material is often in a thermodynamically nonequilibrium state, and conventional constitutive relations or equations of state are often not available. In this method, the closure quantities, such as stress, at each material point are calculated from a molecular dynamics simulation of a group of atoms surrounding the material point. Rather than restricting the multiscale simulation in a small spatial region,more » such as phase interfaces, or crack tips, this multiscale method can be used to consider nonequilibrium thermodynamic effects in a macroscopic domain. This method takes the advantage that the material points only communicate with mesh nodes, not among themselves; therefore molecular dynamics simulations for material points can be performed independently in parallel. The dual domain material point method is chosen for this multiscale method because it can be used in history dependent problems with large deformation without generating numerical noise as material points move across cells, and also because of its convergence and conservation properties. In conclusion, to demonstrate the feasibility and accuracy of this method, we compare the results of a shock wave propagation in a cerium crystal calculated using the direct molecular dynamics simulation with the results from this combined multiscale calculation.« less

Shock waves simulated using the dual domain material point method combined with molecular dynamics

DOE PAGES

Zhang, Duan Z.; Dhakal, Tilak Raj

2017-01-17

Here in this work we combine the dual domain material point method with molecular dynamics in an attempt to create a multiscale numerical method to simulate materials undergoing large deformations with high strain rates. In these types of problems, the material is often in a thermodynamically nonequilibrium state, and conventional constitutive relations or equations of state are often not available. In this method, the closure quantities, such as stress, at each material point are calculated from a molecular dynamics simulation of a group of atoms surrounding the material point. Rather than restricting the multiscale simulation in a small spatial region,more » such as phase interfaces, or crack tips, this multiscale method can be used to consider nonequilibrium thermodynamic effects in a macroscopic domain. This method takes the advantage that the material points only communicate with mesh nodes, not among themselves; therefore molecular dynamics simulations for material points can be performed independently in parallel. The dual domain material point method is chosen for this multiscale method because it can be used in history dependent problems with large deformation without generating numerical noise as material points move across cells, and also because of its convergence and conservation properties. In conclusion, to demonstrate the feasibility and accuracy of this method, we compare the results of a shock wave propagation in a cerium crystal calculated using the direct molecular dynamics simulation with the results from this combined multiscale calculation.« less

How to identify dislocations in molecular dynamics simulations?

NASA Astrophysics Data System (ADS)

Li, Duo; Wang, FengChao; Yang, ZhenYu; Zhao, YaPu

2014-12-01

Dislocations are of great importance in revealing the underlying mechanisms of deformed solid crystals. With the development of computational facilities and technologies, the observations of dislocations at atomic level through numerical simulations are permitted. Molecular dynamics (MD) simulation suggests itself as a powerful tool for understanding and visualizing the creation of dislocations as well as the evolution of crystal defects. However, the numerical results from the large-scale MD simulations are not very illuminating by themselves and there exist various techniques for analyzing dislocations and the deformed crystal structures. Thus, it is a big challenge for the beginners in this community to choose a proper method to start their investigations. In this review, we summarized and discussed up to twelve existing structure characterization methods in MD simulations of deformed crystal solids. A comprehensive comparison was made between the advantages and disadvantages of these typical techniques. We also examined some of the recent advances in the dynamics of dislocations related to the hydraulic fracturing. It was found that the dislocation emission has a significant effect on the propagation and bifurcation of the crack tip in the hydraulic fracturing.

Motions and entropies in proteins as seen in NMR relaxation experiments and molecular dynamics simulations.

PubMed

Allnér, Olof; Foloppe, Nicolas; Nilsson, Lennart

2015-01-22

Molecular dynamics simulations of E. coli glutaredoxin1 in water have been performed to relate the dynamical parameters and entropy obtained in NMR relaxation experiments, with results extracted from simulated trajectory data. NMR relaxation is the most widely used experimental method to obtain data on dynamics of proteins, but it is limited to relatively short timescales and to motions of backbone amides or in some cases (13)C-H vectors. By relating the experimental data to the all-atom picture obtained in molecular dynamics simulations, valuable insights on the interpretation of the experiment can be gained. We have estimated the internal dynamics and their timescales by calculating the generalized order parameters (O) for different time windows. We then calculate the quasiharmonic entropy (S) and compare it to the entropy calculated from the NMR-derived generalized order parameter of the amide vectors. Special emphasis is put on characterizing dynamics that are not expressed through the motions of the amide group. The NMR and MD methods suffer from complementary limitations, with NMR being restricted to local vectors and dynamics on a timescale determined by the rotational diffusion of the solute, while in simulations, it may be difficult to obtain sufficient sampling to ensure convergence of the results. We also evaluate the amount of sampling obtained with molecular dynamics simulations and how it is affected by the length of individual simulations, by clustering of the sampled conformations. We find that two structural turns act as hinges, allowing the α helix between them to undergo large, long timescale motions that cannot be detected in the time window of the NMR dipolar relaxation experiments. We also show that the entropy obtained from the amide vector does not account for correlated motions of adjacent residues. Finally, we show that the sampling in a total of 100 ns molecular dynamics simulation can be increased by around 50%, by dividing the

Molecular dynamics simulations of acoustic absorption by a carbon nanotube

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Molecular dynamics simulations of the dielectric properties of fructose aqueous solutions

NASA Astrophysics Data System (ADS)

Sonoda, Milton T.; Elola, M. Dolores; Skaf, Munir S.

2016-10-01

The static dielectric permittivity and dielectric relaxation properties of fructose aqueous solutions of different concentrations ranging from 1.0 to 4.0 mol l-1 are investigated by means of molecular dynamics simulations. The contributions from intra- and interspecies molecular correlations were computed individually for both the static and frequency-dependent dielectric properties, and the results were compared with the available experimental data. Simulation results in the time- and frequency-domains were analyzed and indicate that the presence of fructose has little effect on the position of the fast, high-frequency (>500 cm-1) components of the dielectric response spectrum. The low-frequency (<0.1 cm-1) components, however, are markedly influenced by sugar concentration. Our analysis indicates that fructose-fructose and fructose-water interactions strongly affect the rotational-diffusion regime of molecular motions in the solutions. Increasing fructose concentration not only enhances sugar-sugar and sugar-water low frequency contributions to the dielectric loss spectrum but also slows down the reorientational dynamics of water molecules. These results are consistent with previous computer simulations carried out for other disaccharide aqueous solutions.

Molecular dynamic simulation of weakly magnetized complex plasmas

NASA Astrophysics Data System (ADS)

Funk, Dylan; Konopka, Uwe; Thomas, Edward

2017-10-01

A complex plasma consists of the usual plasma components (electrons, ions and neutrals), as well as a heavier component made of solid, micrometer-sized particles. The particles are in general highly charged as a result of the interaction with the other plasma components. The static and dynamic properties of a complex plasma such as its crystal structure or wave properties are influenced by many forces acting on the individual particles such as the dust particle interaction (a screened Coulomb interaction), neutral (Epstein) drag, the particle inertia and various plasma drag or thermophoretic forces. To study the behavior of complex plasmas we setup an experiment accompanying molecular dynamic simulation. We will present the approach taken in our simulation and give an overview of experimental situations that we want to cover with our simulation such as the particle charge under microgravity condition as performed on the PK-4 space experiment, or to study the detailed influences of high magnetic fields. This work was supported by the US Dept. of Energy (DE-SC0016330), NSF (PHY-1613087) and JPL/NASA (JPL-RSA 1571699).

Classical Molecular Dynamics Simulation of Nuclear Fuel

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

Devanathan, Ram; Krack, Matthias; Bertolus, Marjorie

2015-10-10

Molecular dynamics simulation is well suited to study primary damage production by irradiation, defect interactions with fission gas atoms, gas bubble nucleation, grain boundary effects on defect and gas bubble evolution in nuclear fuel, and the resulting changes in thermo-mechanical properties. In these simulations, the forces on the ions are dictated by interaction potentials generated by fitting properties of interest to experimental data. The results obtained from the present generation of potentials are qualitatively similar, but quantitatively different. There is a need to refine existing potentials to provide a better representation of the performance of polycrystalline fuel under a varietymore » of operating conditions, and to develop models that are equipped to handle deviations from stoichiometry. In addition to providing insights into fundamental mechanisms governing the behaviour of nuclear fuel, MD simulations can also provide parameters that can be used as inputs for mesoscale models.« less

Using molecular simulation to explore the nanoscale dynamics of the plant kinome.

PubMed

Moffett, Alexander S; Shukla, Diwakar

2018-03-09

Eukaryotic protein kinases (PKs) are a large family of proteins critical for cellular response to external signals, acting as molecular switches. PKs propagate biochemical signals by catalyzing phosphorylation of other proteins, including other PKs, which can undergo conformational changes upon phosphorylation and catalyze further phosphorylations. Although PKs have been studied thoroughly across the domains of life, the structures of these proteins are sparsely understood in numerous groups of organisms, including plants. In addition to efforts towards determining crystal structures of PKs, research on human PKs has incorporated molecular dynamics (MD) simulations to study the conformational dynamics underlying the switching of PK function. This approach of experimental structural biology coupled with computational biophysics has led to improved understanding of how PKs become catalytically active and why mutations cause pathological PK behavior, at spatial and temporal resolutions inaccessible to current experimental methods alone. In this review, we argue for the value of applying MD simulation to plant PKs. We review the basics of MD simulation methodology, the successes achieved through MD simulation in animal PKs, and current work on plant PKs using MD simulation. We conclude with a discussion of the future of MD simulations and plant PKs, arguing for the importance of molecular simulation in the future of plant PK research. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

Molecular Dynamics Simulations to Clarify the Concentration Dependency of Protein Aggregation

NASA Astrophysics Data System (ADS)

Nishikawa, Naohiro; Sakae, Yoshitake; Okamoto, Yuko

We examined the concentration dependency of amyloid protein aggregation by using several molecular dynamics simulations, which were performed with different concentrations for each system. For these simulations, we used a fragment of amyloid-β, which is believed to be the cause of Alzheimer's disease, as our simulation system. We found that high concentration of amyloid peptides promotes the formation of β-structures which is the origin of amyloid fibrils.

Unraveling HIV protease flaps dynamics by Constant pH Molecular Dynamics simulations.

PubMed

Soares, Rosemberg O; Torres, Pedro H M; da Silva, Manuela L; Pascutti, Pedro G

2016-08-01

The active site of HIV protease (HIV-PR) is covered by two flaps. These flaps are known to be essential for the catalytic activity of the HIV-PR, but their exact conformations at the different stages of the enzymatic pathway remain subject to debate. Understanding the correct functional dynamics of the flaps might aid the development of new HIV-PR inhibitors. It is known that, the HIV-PR catalytic efficiency is pH-dependent, likely due to the influence of processes such as charge transfer and protonation/deprotonation of ionizable residues. Several Molecular Dynamics (MD) simulations have reported information about the HIV-PR flaps. However, in MD simulations the protonation of a residue is fixed and thus it is not possible to study the correlation between conformation and protonation state. To address this shortcoming, this work attempts to capture, through Constant pH Molecular Dynamics (CpHMD), the conformations of the apo, substrate-bound and inhibitor-bound HIV-PR, which differ drastically in their flap arrangements. The results show that the HIV-PR flaps conformations are defined by the protonation of the catalytic residues Asp25/Asp25' and that these residues are sensitive to pH changes. This study suggests that the catalytic aspartates can modulate the opening of the active site and substrate binding. Copyright © 2016 Elsevier Inc. All rights reserved.

Avoiding Defect Nucleation during Equilibration in Molecular Dynamics Simulations with ReaxFF

DTIC Science & Technology

2015-04-01

respectively. All simulations are performed using the LAMMPS computer code.12 2 Fig. 1 a) Initial and b) final configurations of the molecular centers...Plimpton S. Fast parallel algorithms for short-range molecular dynamics. Comput J Phys. 1995;117:1–19. (Software available at http:// lammps .sandia.gov

Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations.

PubMed

Lei, Hongxing; Wu, Chun; Liu, Haiguang; Duan, Yong

2007-03-20

High-accuracy ab initio folding has remained an elusive objective despite decades of effort. To explore the folding landscape of villin headpiece subdomain HP35, we conducted two sets of replica exchange molecular dynamics for 200 ns each and three sets of conventional microsecond-long molecular dynamics simulations, using AMBER FF03 force field and a generalized-Born solvation model. The protein folded consistently to the native state; the lowest C(alpha)-rmsd from the x-ray structure was 0.46 A, and the C(alpha)- rmsd of the center of the most populated cluster was 1.78 A at 300 K. ab initio simulations have previously not reached this level. The folding landscape of HP35 can be partitioned into the native, denatured, and two intermediate-state regions. The native state is separated from the major folding intermediate state by a small barrier, whereas a large barrier exists between the major folding intermediate and the denatured states. The melting temperature T(m) = 339 K extracted from the heat-capacity profile was in close agreement with the experimentally derived T(m) = 342 K. A comprehensive picture of the kinetics and thermodynamics of HP35 folding emerges when the results from replica exchange and conventional molecular dynamics simulations are combined.

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).

Nanomaterials under extreme environments: A study of structural and dynamic properties using reactive molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Shekhar, Adarsh

Nanotechnology is becoming increasingly important with the continuing advances in experimental techniques. As researchers around the world are trying to expand the current understanding of the behavior of materials at the atomistic scale, the limited resolution of equipment, both in terms of time and space, act as roadblocks to a comprehensive study. Numerical methods, in general and molecular dynamics, in particular act as able compliment to the experiments in our quest for understanding material behavior. In this research work, large scale molecular dynamics simulations to gain insight into the mechano-chemical behavior under extreme conditions of a variety of systems with many real world applications. The body of this work is divided into three parts, each covering a particular system: 1) Aggregates of aluminum nanoparticles are good solid fuel due to high flame propagation rates. Multi-million atom molecular dynamics simulations reveal the mechanism underlying higher reaction rate in a chain of aluminum nanoparticles as compared to an isolated nanoparticle. This is due to the penetration of hot atoms from reacting nanoparticles to an adjacent, unreacted nanoparticle, which brings in external heat and initiates exothermic oxidation reactions. 2) Cavitation bubbles readily occur in fluids subjected to rapid changes in pressure. We use billion-atom reactive molecular dynamics simulations on a 163,840-processor BlueGene/P supercomputer to investigate chemical and mechanical damages caused by shock-induced collapse of nanobubbles in water near amorphous silica. Collapse of an empty nanobubble generates high-speed nanojet, resulting in the formation of a pit on the surface. The pit contains a large number of silanol groups and its volume is found to be directly proportional to the volume of the nanobubble. The gas-filled bubbles undergo partial collapse and consequently the damage on the silica surface is mitigated. 3) The structure and dynamics of water confined in

In situ structure and dynamics of DNA origami determined through molecular dynamics simulations

PubMed Central

Yoo, Jejoong; Aksimentiev, Aleksei

2013-01-01

The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic, and solvent-mediated forces. Whereas the global structural features of such relaxed conformations conform to the target designs, local deformations are abundant and vary in magnitude along the structures. In contrast to their free-solution conformation, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation. We find the DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanical properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects. PMID:24277840

In situ structure and dynamics of DNA origami determined through molecular dynamics simulations.

PubMed

Yoo, Jejoong; Aksimentiev, Aleksei

2013-12-10

The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic, and solvent-mediated forces. Whereas the global structural features of such relaxed conformations conform to the target designs, local deformations are abundant and vary in magnitude along the structures. In contrast to their free-solution conformation, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation. We find the DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanical properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects.

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

Molecular Dynamics Simulations with Quantum Mechanics/Molecular Mechanics and Adaptive Neural Networks.

PubMed

Shen, Lin; Yang, Weitao

2018-03-13

Direct molecular dynamics (MD) simulation with ab initio quantum mechanical and molecular mechanical (QM/MM) methods is very powerful for studying the mechanism of chemical reactions in a complex environment but also very time-consuming. The computational cost of QM/MM calculations during MD simulations can be reduced significantly using semiempirical QM/MM methods with lower accuracy. To achieve higher accuracy at the ab initio QM/MM level, a correction on the existing semiempirical QM/MM model is an attractive idea. Recently, we reported a neural network (NN) method as QM/MM-NN to predict the potential energy difference between semiempirical and ab initio QM/MM approaches. The high-level results can be obtained using neural network based on semiempirical QM/MM MD simulations, but the lack of direct MD samplings at the ab initio QM/MM level is still a deficiency that limits the applications of QM/MM-NN. In the present paper, we developed a dynamic scheme of QM/MM-NN for direct MD simulations on the NN-predicted potential energy surface to approximate ab initio QM/MM MD. Since some configurations excluded from the database for NN training were encountered during simulations, which may cause some difficulties on MD samplings, an adaptive procedure inspired by the selection scheme reported by Behler [ Behler Int. J. Quantum Chem. 2015 , 115 , 1032 ; Behler Angew. Chem., Int. Ed. 2017 , 56 , 12828 ] was employed with some adaptions to update NN and carry out MD iteratively. We further applied the adaptive QM/MM-NN MD method to the free energy calculation and transition path optimization on chemical reactions in water. The results at the ab initio QM/MM level can be well reproduced using this method after 2-4 iteration cycles. The saving in computational cost is about 2 orders of magnitude. It demonstrates that the QM/MM-NN with direct MD simulations has great potentials not only for the calculation of thermodynamic properties but also for the characterization of

Lipid Interaction Sites on Channels, Transporters and Receptors: Recent Insights from Molecular Dynamics Simulations

PubMed Central

Hedger, George; Sansom, Mark S. P.

2017-01-01

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

METAGUI. A VMD interface for analyzing metadynamics and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Biarnés, Xevi; Pietrucci, Fabio; Marinelli, Fabrizio; Laio, Alessandro

2012-01-01

We present a new computational tool, METAGUI, which extends the VMD program with a graphical user interface that allows constructing a thermodynamic and kinetic model of a given process simulated by large-scale molecular dynamics. The tool is specially designed for analyzing metadynamics based simulations. The huge amount of diverse structures generated during such a simulation is partitioned into a set of microstates (i.e. structures with similar values of the collective variables). Their relative free energies are then computed by a weighted-histogram procedure and the most relevant free energy wells are identified by diagonalization of the rate matrix followed by a commitor analysis. All this procedure leads to a convenient representation of the metastable states and long-time kinetics of the system which can be compared with experimental data. The tool allows to seamlessly switch between a collective variables space representation of microstates and their atomic structure representation, which greatly facilitates the set-up and analysis of molecular dynamics simulations. METAGUI is based on the output format of the PLUMED plugin, making it compatible with a number of different molecular dynamics packages like AMBER, NAMD, GROMACS and several others. The METAGUI source files can be downloaded from the PLUMED web site ( http://www.plumed-code.org). Program summaryProgram title: METAGUI Catalogue identifier: AEKH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKH_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 3 No. of lines in distributed program, including test data, etc.: 117 545 No. of bytes in distributed program, including test data, etc.: 8 516 203 Distribution format: tar.gz Programming language: TK/TCL, Fortran Computer: Any computer with a VMD installation and capable of running an executable produced by a gfortran compiler Operating

Characterization of Hydrophobic Interactions of Polymers with Water and Phospholipid Membranes Using Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Drenscko, Mihaela

Polymers and lipid membranes are both essential soft materials. The structure and hydrophobicity/hydrophilicity of polymers, as well as the solvent they are embedded in, ultimately determines their size and shape. Understating the variation of shape of the polymer as well as its interactions with model biological membranes can assist in understanding the biocompatibility of the polymer itself. Computer simulations, in particular molecular dynamics, can aid in characterization of the interaction of polymers with solvent, as well as polymers with model membranes. In this thesis, molecular dynamics serve to describe polymer interactions with a solvent (water) and with a lipid membrane. To begin with, we characterize the hydrophobic collapse of single polystyrene chains in water using molecular dynamics simulations. Specifically, we calculate the potential of mean force for the collapse of a single polystyrene chain in water using metadynamics, comparing the results between all atomistic with coarse-grained molecular simulation. We next explore the scaling behavior of the collapsed globular shape at the minimum energy configuration, characterized by the radius of gyration, as a function of chain length. The exponent is close to one third, consistent with that predicted for a polymer chain in bad solvent. We also explore the scaling behavior of the Solvent Accessible Surface Area (SASA) as a function of chain length, finding a similar exponent for both all-atomistic and coarse-grained simulations. Furthermore, calculation of the local water density as a function of chain length near the minimum energy configuration suggests that intermediate chain lengths are more likely to form dewetted states, as compared to shorter or longer chain lengths. Next, in order to investigate the molecular interactions between single hydrophobic polymer chains and lipids in biological membranes and at lipid membrane/solvent interface, we perform a series of molecular dynamics simulations of

Molecular dynamics and dynamic Monte-Carlo simulation of irradiation damage with focused ion beams

NASA Astrophysics Data System (ADS)

Ohya, Kaoru

2017-03-01

The focused ion beam (FIB) has become an important tool for micro- and nanostructuring of samples such as milling, deposition and imaging. However, this leads to damage of the surface on the nanometer scale from implanted projectile ions and recoiled material atoms. It is therefore important to investigate each kind of damage quantitatively. We present a dynamic Monte-Carlo (MC) simulation code to simulate the morphological and compositional changes of a multilayered sample under ion irradiation and a molecular dynamics (MD) simulation code to simulate dose-dependent changes in the backscattering-ion (BSI)/secondary-electron (SE) yields of a crystalline sample. Recent progress in the codes for research to simulate the surface morphology and Mo/Si layers intermixing in an EUV lithography mask irradiated with FIBs, and the crystalline orientation effect on BSI and SE yields relating to the channeling contrast in scanning ion microscopes, is also presented.

A molecular dynamics simulation study of chloroform

NASA Astrophysics Data System (ADS)

Tironi, Ilario G.; van Gunsteren, Wilfred F.

Three different chloroform models have been investigated using molecular dynamics computer simulation. The thermodynamic, structural and dynamic properties of the various models were investigated in detail. In particular, the potential energies, diffusion coefficients and rotational correlation times obtained for each model are compared with experiment. It is found that the theory of rotational Brownian motion fails in describing the rotational diffusion of chloroform. The force field of Dietz and Heinzinger was found to give good overall agreement with experiment. An extended investigation of this chloroform model has been performed. Values are reported for the isothermal compressibility, the thermal expansion coefficient and the constant volume heat capacity. The values agree well with experiment. The static and frequency dependent dielectric permittivity were computed from a 1·2 ns simulation conducted under reaction field boundary conditions. Considering the fact that the model is rigid with fixed partial charges, the static dielectric constant and Debye relaxation time compare well with experiment. From the same simulation the shear viscosity was computed using the off-diagonal elements of the pressure tensor, both via an Einstein type relation and via a Green-Kubo equation. The calculated viscosities show good agreement with experimental values. The excess Helmholtz energy is calculated using the thermodynamic integration technique and simulations of 50 and 80 ps. The value obtained for the excess Helmholtz energy matches the theoretical value within a few per cent.

Use of multiple picosecond high-mass molecular dynamics simulations to predict crystallographic B-factors of folded globular proteins.

PubMed

Pang, Yuan-Ping

2016-09-01

Predicting crystallographic B-factors of a protein from a conventional molecular dynamics simulation is challenging, in part because the B-factors calculated through sampling the atomic positional fluctuations in a picosecond molecular dynamics simulation are unreliable, and the sampling of a longer simulation yields overly large root mean square deviations between calculated and experimental B-factors. This article reports improved B-factor prediction achieved by sampling the atomic positional fluctuations in multiple picosecond molecular dynamics simulations that use uniformly increased atomic masses by 100-fold to increase time resolution. Using the third immunoglobulin-binding domain of protein G, bovine pancreatic trypsin inhibitor, ubiquitin, and lysozyme as model systems, the B-factor root mean square deviations (mean ± standard error) of these proteins were 3.1 ± 0.2-9 ± 1 Å 2 for Cα and 7.3 ± 0.9-9.6 ± 0.2 Å 2 for Cγ, when the sampling was done for each of these proteins over 20 distinct, independent, and 50-picosecond high-mass molecular dynamics simulations with AMBER forcefield FF12MC or FF14SB. These results suggest that sampling the atomic positional fluctuations in multiple picosecond high-mass molecular dynamics simulations may be conducive to a priori prediction of crystallographic B-factors of a folded globular protein.

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

PubMed

Sapay, Nicolas; Nurisso, Alessandra; Imberty, Anne

2013-01-01

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

Tensile strength of Fe-Ni and Mg-Al nanocomposites: Molecular dynamic simulations

NASA Astrophysics Data System (ADS)

Pogorelko, V. V.; Mayer, A. E.

2018-01-01

In this work, molecular dynamic simulations of the tensile strength of Fe-Ni and Mg-Al nanocomposites in the conditions of high-rate uniaxial tension were carried out. Two different mechanisms of fracture were identified. In the case of nickel inclusion in iron matrix, the fracture begins on the interface between the inclusion and the matrix, a formed void penetrates both into the inclusion and into the matrix; presence of inclusion reduces the tensile strength. In the case of aluminum inclusion in magnesium matrix, fracture takes place into magnesium matrix and does not touch the inclusion; presence of inclusion has practically no effect on the tensile strength. Molecular dynamic simulations were carried out in a wide range of strain rates and temperatures.

Multiscale Molecular Dynamics Simulations of Beta-Amyloid Interactions with Neurons

NASA Astrophysics Data System (ADS)

Qiu, Liming; Vaughn, Mark; Cheng, Kelvin

2012-10-01

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

Validation of Potential Models for Li2O in Classical Molecular Dynamics Simulation

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

Oda, Takuji; Oya, Yasuhisa; Tanaka, Satoru

2007-08-01

Four Buckingham-type pairwise potential models for Li2O were assessed by molecular static and dynamics simulations. In the static simulation, all models afforded acceptable agreement with experimental values and ab initio calculation results for the crystalline properties. Moreover, the superionic phase transition was realized in the dynamics simulation. However, the Li diffusivity and the lattice expansion were not adequately reproduced at the same time by any model. When using these models in future radiation simulation, these features should be taken into account, in order to reduce the model dependency of the results.

Molecular Dynamics Simulations of Carbon Nanotubes in Water

NASA Technical Reports Server (NTRS)

Walther, J. H.; Jaffe, R.; Halicioglu, T.; Koumoutsakos, P.

2000-01-01

We study the hydrophobic/hydrophilic behavior of carbon nanotubes using molecular dynamics simulations. The energetics of the carbon-water interface are mainly dispersive but in the present study augmented with a carbon quadrupole term acting on the charge sites of the water. The simulations indicate that this contribution is negligible in terms of modifying the structural properties of water at the interface. Simulations of two carbon nanotubes in water display a wetting and drying of the interface between the nanotubes depending on their initial spacing. Thus, initial tube spacings of 7 and 8 A resulted in a drying of the interface whereas spacing of > 9 A remain wet during the course of the simulation. Finally, we present a novel particle-particle-particle-mesh algorithm for long range potentials which allows for general (curvilinear) meshes and "black-box" fast solvers by adopting an influence matrix technique.

On the application of accelerated molecular dynamics to liquid water simulations.

PubMed

de Oliveira, César Augusto F; Hamelberg, Donald; McCammon, J Andrew

2006-11-16

Our group recently proposed a robust bias potential function that can be used in an efficient all-atom accelerated molecular dynamics (MD) approach to simulate the transition of high energy barriers without any advance knowledge of the potential-energy landscape. The main idea is to modify the potential-energy surface by adding a bias, or boost, potential in regions close to the local minima, such that all transitions rates are increased. By applying the accelerated MD simulation method to liquid water, we observed that this new simulation technique accelerates the molecular motion without losing its microscopic structure and equilibrium properties. Our results showed that the application of a small boost energy on the potential-energy surface significantly reduces the statistical inefficiency of the simulation while keeping all the other calculated properties unchanged. On the other hand, although aggressive acceleration of the dynamics simulation increases the self-diffusion coefficient of water molecules greatly and dramatically reduces the correlation time of the simulation, configurations representative of the true structure of liquid water are poorly sampled. Our results also showed the strength and robustness of this simulation technique, which confirm this approach as a very useful and promising tool to extend the time scale of the all-atom simulations of biological system with explicit solvent models. However, we should keep in mind that there is a compromise between the strength of the boost applied in the simulation and the reproduction of the ensemble average properties.

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

PubMed

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

2016-03-21

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

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins.

PubMed

Karp, Jerome M; Eryilmaz, Ertan; Erylimaz, Ertan; Cowburn, David

2015-01-01

There has been a longstanding interest in being able to accurately predict NMR chemical shifts from structural data. Recent studies have focused on using molecular dynamics (MD) simulation data as input for improved prediction. Here we examine the accuracy of chemical shift prediction for intein systems, which have regions of intrinsic disorder. We find that using MD simulation data as input for chemical shift prediction does not consistently improve prediction accuracy over use of a static X-ray crystal structure. This appears to result from the complex conformational ensemble of the disordered protein segments. We show that using accelerated molecular dynamics (aMD) simulations improves chemical shift prediction, suggesting that methods which better sample the conformational ensemble like aMD are more appropriate tools for use in chemical shift prediction for proteins with disordered regions. Moreover, our study suggests that data accurately reflecting protein dynamics must be used as input for chemical shift prediction in order to correctly predict chemical shifts in systems with disorder.

Rheology of wormlike micellar fluids from Brownian and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Padding, J. T.; Boek, E. S.; Briels, W. J.

2005-11-01

There is a great need for understanding the link between the detailed chemistry of surfactants, forming wormlike micelles, and their macroscopic rheological properties. In this paper we show how this link may be explored through particle simulations. First we review an existing bead-spring model. We find that shear flow enhances the formation of rings at the expense of linear chains. The shear viscosity of this model is dominated by solvent contributions, however, and the link with the chemistry of the surfactants is missing. We introduce a more realistic Brownian dynamics model, the parameters of which are measured from atomistic molecular dynamics simulations.

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.

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.

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.

Classical molecular dynamics simulations for non-equilibrium correlated plasmas

NASA Astrophysics Data System (ADS)

Ferri, S.; Calisti, A.; Talin, B.

2017-03-01

A classical molecular dynamics model was recently extended to simulate neutral multi-component plasmas where various charge states of the same atom and electrons coexist. It is used to investigate the plasma effects on the ion charge and on the ionization potential in dense plasmas. Different simulated statistical properties will show that the concept of isolated particles is lost in such correlated plasmas. The charge equilibration is discussed for a carbon plasma at solid density and investigation on the charge distribution and on the ionization potential depression (IPD) for aluminum plasmas is discussed with reference to existing experiments.

DynamO: a free O(N) general event-driven molecular dynamics simulator.

PubMed

Bannerman, M N; Sargant, R; Lue, L

2011-11-30

Molecular dynamics algorithms for systems of particles interacting through discrete or "hard" potentials are fundamentally different to the methods for continuous or "soft" potential systems. Although many software packages have been developed for continuous potential systems, software for discrete potential systems based on event-driven algorithms are relatively scarce and specialized. We present DynamO, a general event-driven simulation package, which displays the optimal O(N) asymptotic scaling of the computational cost with the number of particles N, rather than the O(N) scaling found in most standard algorithms. DynamO provides reference implementations of the best available event-driven algorithms. These techniques allow the rapid simulation of both complex and large (>10(6) particles) systems for long times. The performance of the program is benchmarked for elastic hard sphere systems, homogeneous cooling and sheared inelastic hard spheres, and equilibrium Lennard-Jones fluids. This software and its documentation are distributed under the GNU General Public license and can be freely downloaded from http://marcusbannerman.co.uk/dynamo. Copyright © 2011 Wiley Periodicals, Inc.

Combined Molecular Dynamics Simulation-Molecular-Thermodynamic Theory Framework for Predicting Surface Tensions.

PubMed

Sresht, Vishnu; Lewandowski, Eric P; Blankschtein, Daniel; Jusufi, Arben

2017-08-22

A molecular modeling approach is presented with a focus on quantitative predictions of the surface tension of aqueous surfactant solutions. The approach combines classical Molecular Dynamics (MD) simulations with a molecular-thermodynamic theory (MTT) [ Y. J. Nikas, S. Puvvada, D. Blankschtein, Langmuir 1992 , 8 , 2680 ]. The MD component is used to calculate thermodynamic and molecular parameters that are needed in the MTT model to determine the surface tension isotherm. The MD/MTT approach provides the important link between the surfactant bulk concentration, the experimental control parameter, and the surfactant surface concentration, the MD control parameter. We demonstrate the capability of the MD/MTT modeling approach on nonionic alkyl polyethylene glycol surfactants at the air-water interface and observe reasonable agreement of the predicted surface tensions and the experimental surface tension data over a wide range of surfactant concentrations below the critical micelle concentration. Our modeling approach can be extended to ionic surfactants and their mixtures with both ionic and nonionic surfactants at liquid-liquid interfaces.

Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

PubMed Central

Tambunan, Usman Sumo Friend; Nasution, Mochammad Arfin Fardiansyah; Azhima, Fauziah; Parikesit, Arli Aditya; Toepak, Erwin Prasetya; Idrus, Syarifuddin; Kerami, Djati

2017-01-01

Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔGbinding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever. PMID:28469408

Molecular dynamics simulation and NMR investigation of the association of the β-blockers atenolol and propranolol with a chiral molecular micelle

NASA Astrophysics Data System (ADS)

Morris, Kevin F.; Billiot, Eugene J.; Billiot, Fereshteh H.; Hoffman, Charlene B.; Gladis, Ashley A.; Lipkowitz, Kenny B.; Southerland, William M.; Fang, Yayin

2015-08-01

Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two β-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S)-propranolol associated more strongly with the molecular micelle than (R)-propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Molecular dynamics simulations of classical sound absorption in a monatomic gas

NASA Astrophysics Data System (ADS)

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

2018-05-01

Sound wave propagation in argon gas is simulated using molecular dynamics (MD) in order to determine the attenuation of acoustic energy due to classical (viscous and thermal) losses at high frequencies. In addition, a method is described to estimate attenuation of acoustic energy using the thermodynamic concept of exergy. The results are compared against standing wave theory and the predictions of the theory of continuum mechanics. Acoustic energy losses are studied by evaluating various attenuation parameters and by comparing the changes in behavior at three different frequencies. This study demonstrates acoustic absorption effects in a gas simulated in a thermostatted molecular simulation and quantifies the classical losses in terms of the sound attenuation constant. The approach can be extended to further understanding of acoustic loss mechanisms in the presence of nanoscale porous materials in the simulation domain.

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.

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.

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.

Dielectric relaxation of ethylene carbonate and propylene carbonate from molecular dynamics simulations

DOE PAGES

Chaudhari, Mangesh I.; You, Xinli; Pratt, Lawrence R.; ...

2015-11-24

Ethylene carbonate (EC) and propylene carbonate (PC) are widely used solvents in lithium (Li)-ion batteries and supercapacitors. Ion dissolution and diffusion in those media are correlated with solvent dielectric responses. Here, we use all-atom molecular dynamics simulations of the pure solvents to calculate dielectric constants and relaxation times, and molecular mobilities. The computed results are compared with limited available experiments to assist more exhaustive studies of these important characteristics. As a result, the observed agreement is encouraging and provides guidance for further validation of force-field simulation models for EC and PC solvents.

Clustering effects in ionic polymers: Molecular dynamics simulations.

PubMed

Agrawal, Anupriya; Perahia, Dvora; Grest, Gary S

2015-08-01

Ionic clusters control the structure, dynamics, and transport in soft matter. Incorporating a small fraction of ionizable groups in polymers substantially reduces the mobility of the macromolecules in melts. These ionic groups often associate into random clusters in melts, where the distribution and morphology of the clusters impact the transport in these materials. Here, using molecular dynamic simulations we demonstrate a clear correlation between cluster size and morphology with the polymer mobility in melts of sulfonated polystyrene. We show that in low dielectric media ladderlike clusters that are lower in energy compared with spherical assemblies are formed. Reducing the electrostatic interactions by enhancing the dielectric constant leads to morphological transformation from ladderlike clusters to globular assemblies. Decrease in electrostatic interaction significantly enhances the mobility of the polymer.

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.

Spontaneous formation of polyglutamine nanotubes with molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Laghaei, Rozita; Mousseau, Normand

2010-04-01

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

Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale.

PubMed

Chavent, Matthieu; Duncan, Anna L; Sansom, Mark Sp

2016-10-01

Molecular dynamics simulations provide a computational tool to probe membrane proteins and systems at length scales ranging from nanometers to close to a micrometer, and on microsecond timescales. All atom and coarse-grained simulations may be used to explore in detail the interactions of membrane proteins and specific lipids, yielding predictions of lipid binding sites in good agreement with available structural data. Building on the success of protein-lipid interaction simulations, larger scale simulations reveal crowding and clustering of proteins, resulting in slow and anomalous diffusional dynamics, within realistic models of cell membranes. Current methods allow near atomic resolution simulations of small membrane organelles, and of enveloped viruses to be performed, revealing key aspects of their structure and functionally important dynamics. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Consistent Principal Component Modes from Molecular Dynamics Simulations of Proteins.

PubMed

Cossio-Pérez, Rodrigo; Palma, Juliana; Pierdominici-Sottile, Gustavo

2017-04-24

Principal component analysis is a technique widely used for studying the movements of proteins using data collected from molecular dynamics simulations. In spite of its extensive use, the technique has a serious drawback: equivalent simulations do not afford the same PC-modes. In this article, we show that concatenating equivalent trajectories and calculating the PC-modes from the concatenated one significantly enhances the reproducibility of the results. Moreover, the consistency of the modes can be systematically improved by adding more individual trajectories to the concatenated one.

The Molecular Structure of a Phosphatidylserine Bilayer Determined by Scattering and Molecular Dynamics Simulations

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

Pan, Jianjun; Cheng, Xiaolin; Monticelli, Luca

2014-01-01

Phosphatidylserine (PS) lipids play essential roles in biological processes, including enzyme activation and apoptosis. We report on the molecular structure and atomic scale interactions of a fluid bilayer composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS). A scattering density profile model, aided by molecular dynamics (MD) simulations, was developed to jointly refine different contrast small-angle neutron and X-ray scattering data, which yielded a lipid area of 62.7 A2 at 25 C. MD simulations with POPS lipid area constrained at different values were also performed using all-atom and aliphatic united-atom models. The optimal simulated bilayer was obtained using a model-free comparison approach. Examination of themore » simulated bilayer, which agrees best with the experimental scattering data, reveals a preferential interaction between Na+ ions and the terminal serine and phosphate moieties. Long-range inter-lipid interactions were identified, primarily between the positively charged ammonium, and the negatively charged carboxylic and phosphate oxygens. The area compressibility modulus KA of the POPS bilayer was derived by quantifying lipid area as a function of surface tension from area-constrained MD simulations. It was found that POPS bilayers possess a much larger KA than that of neutral phosphatidylcholine lipid bilayers. We propose that the unique molecular features of POPS bilayers may play an important role in certain physiological functions.« less

Substructured multibody molecular dynamics.

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

Grest, Gary Stephen; Stevens, Mark Jackson; Plimpton, Steven James

2006-11-01

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

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

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

Hardy, David J., E-mail: dhardy@illinois.edu; Schulten, Klaus; Wolff, Matthew A.

2016-03-21

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

Protecting High Energy Barriers: A New Equation to Regulate Boost Energy in Accelerated Molecular Dynamics Simulations.

PubMed

Sinko, William; de Oliveira, César Augusto F; Pierce, Levi C T; McCammon, J Andrew

2012-01-10

Molecular dynamics (MD) is one of the most common tools in computational chemistry. Recently, our group has employed accelerated molecular dynamics (aMD) to improve the conformational sampling over conventional molecular dynamics techniques. In the original aMD implementation, sampling is greatly improved by raising energy wells below a predefined energy level. Recently, our group presented an alternative aMD implementation where simulations are accelerated by lowering energy barriers of the potential energy surface. When coupled with thermodynamic integration simulations, this implementation showed very promising results. However, when applied to large systems, such as proteins, the simulation tends to be biased to high energy regions of the potential landscape. The reason for this behavior lies in the boost equation used since the highest energy barriers are dramatically more affected than the lower ones. To address this issue, in this work, we present a new boost equation that prevents oversampling of unfavorable high energy conformational states. The new boost potential provides not only better recovery of statistics throughout the simulation but also enhanced sampling of statistically relevant regions in explicit solvent MD simulations.

Hamiltonian adaptive resolution molecular dynamics simulation of infrared dielectric functions of liquids

NASA Astrophysics Data System (ADS)

Wang, C. C.; Tan, J. Y.; Liu, L. H.

2018-05-01

Hamiltonian adaptive resolution scheme (H-AdResS), which allows to simulate materials by treating different domains of the system at different levels of resolution, is a recently proposed atomistic/coarse-grained multiscale model. In this work, a scheme to calculate the dielectric functions of liquids on account of H-AdResS is presented. In the proposed H-AdResS dielectric-function calculation scheme (DielectFunctCalS), the corrected molecular dipole moments are calculated by multiplying molecular dipole moment by the weighting fraction of the molecular mapping point. As the widths of all-atom and hybrid regions show different degrees of influence on the dielectric functions, a prefactor is multiplied to eliminate the effects of all-atom and hybrid region widths. Since one goal of using the H-AdResS method is to reduce computational costs, widths of the all-atom region and the hybrid region can be reduced considering that the coarse-grained simulation is much more timesaving compared to atomistic simulation. Liquid water and ethanol are taken as test cases to validate the DielectFunctCalS. The H-AdResS DielectFunctCalS results are in good agreement with all-atom molecular dynamics simulations. The accuracy of the H-AdResS results, together with all-atom molecular dynamics results, depends heavily on the choice of the force field and force field parameters. The H-AdResS DielectFunctCalS allows us to calculate the dielectric functions of macromolecule systems with high efficiency and makes the dielectric function calculations of large biomolecular systems possible.

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.

Molecular dynamics simulation of nonlinear spectroscopies of intermolecular motions in liquid water.

PubMed

Yagasaki, Takuma; Saito, Shinji

2009-09-15

Water is the most extensively studied of liquids because of both its ubiquity and its anomalous thermodynamic and dynamic properties. The properties of water are dominated by hydrogen bonds and hydrogen bond network rearrangements. Fundamental information on the dynamics of liquid water has been provided by linear infrared (IR), Raman, and neutron-scattering experiments; molecular dynamics simulations have also provided insights. Recently developed higher-order nonlinear spectroscopies open new windows into the study of the hydrogen bond dynamics of liquid water. For example, the vibrational lifetimes of stretches and a bend, intramolecular features of water dynamics, can be accurately measured and are found to be on the femtosecond time scale at room temperature. Higher-order nonlinear spectroscopy is expressed by a multitime correlation function, whereas traditional linear spectroscopy is given by a one-time correlation function. Thus, nonlinear spectroscopy yields more detailed information on the dynamics of condensed media than linear spectroscopy. In this Account, we describe the theoretical background and methods for calculating higher order nonlinear spectroscopy; equilibrium and nonequilibrium molecular dynamics simulations, and a combination of both, are used. We also present the intermolecular dynamics of liquid water revealed by fifth-order two-dimensional (2D) Raman spectroscopy and third-order IR spectroscopy. 2D Raman spectroscopy is sensitive to couplings between modes; the calculated 2D Raman signal of liquid water shows large anharmonicity in the translational motion and strong coupling between the translational and librational motions. Third-order IR spectroscopy makes it possible to examine the time-dependent couplings. The 2D IR spectra and three-pulse photon echo peak shift show the fast frequency modulation of the librational motion. A significant effect of the translational motion on the fast frequency modulation of the librational motion is

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.

Mechanical response of two polyimides through coarse-grained molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sudarkodi, V.; Sooraj, K.; Nair, Nisanth N.; Basu, Sumit; Parandekar, Priya V.; Sinha, Nishant K.; Prakash, Om; Tsotsis, Tom

2018-03-01

Coarse-grained molecular dynamics (MD) simulations allow us to predict the mechanical responses of polymers, starting merely with a description of their molecular architectures. It is interesting to ask whether, given two competing molecular architectures, coarse-grained MD simulations can predict the differences that can be expected in their mechanical responses. We have studied two crosslinked polyimides PMR15 and HFPE52—both used in high- temperature applications—to assess whether the subtle differences in their uniaxial stress-strain responses, revealed by experiments, can be reproduced by carefully coarse-grained MD models. The coarse graining procedure for PMR15 is outlined in this work, while the coarse grain forcefields for HFPE52 are borrowed from an earlier one (Pandiyan et al 2015 Macromol. Theory Simul. 24 513-20). We show that the stress-strain responses of both these polyimides are qualitatively reproduced, and important insights into their deformation and failure mechanisms are obtained. More importantly, the differences in the molecular architecture between the polyimides carry over to the differences in the stress-strain responses in a manner that parallels the experimental results. A critical assessment of the successes and shortcomings of predicting mechanical responses through coarse-grained MD simulations has been made.

Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

PubMed

Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

2015-12-15

Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to

Development of massive multilevel molecular dynamics simulation program, Platypus (PLATform for dYnamic Protein Unified Simulation), for the elucidation of protein functions.

PubMed

Takano, Yu; Nakata, Kazuto; Yonezawa, Yasushige; Nakamura, Haruki

2016-05-05

A massively parallel program for quantum mechanical-molecular mechanical (QM/MM) molecular dynamics simulation, called Platypus (PLATform for dYnamic Protein Unified Simulation), was developed to elucidate protein functions. The speedup and the parallelization ratio of Platypus in the QM and QM/MM calculations were assessed for a bacteriochlorophyll dimer in the photosynthetic reaction center (DIMER) on the K computer, a massively parallel computer achieving 10 PetaFLOPs with 705,024 cores. Platypus exhibited the increase in speedup up to 20,000 core processors at the HF/cc-pVDZ and B3LYP/cc-pVDZ, and up to 10,000 core processors by the CASCI(16,16)/6-31G** calculations. We also performed excited QM/MM-MD simulations on the chromophore of Sirius (SIRIUS) in water. Sirius is a pH-insensitive and photo-stable ultramarine fluorescent protein. Platypus accelerated on-the-fly excited-state QM/MM-MD simulations for SIRIUS in water, using over 4000 core processors. In addition, it also succeeded in 50-ps (200,000-step) on-the-fly excited-state QM/MM-MD simulations for the SIRIUS in water. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Will molecular dynamics simulations of proteins ever reach equilibrium?

PubMed

Genheden, Samuel; Ryde, Ulf

2012-06-28

We show that conformational entropies calculated for five proteins and protein-ligand complexes with dihedral-distribution histogramming, the von Mises approach, or quasi-harmonic analysis do not converge to any useful precision even if molecular dynamics (MD) simulations of 380-500 ns length are employed (the uncertainty is 12-89 kJ mol(-1)). To explain this, we suggest a simple protein model involving dihedrals with effective barriers forming a uniform distribution and show that for such a model, the entropy increases logarithmically with time until all significantly populated dihedral states have been sampled, in agreement with the simulations (during the simulations, 52-70% of the available dihedral phase space has been visited). This is also confirmed by the analysis of the trajectories of a 1 ms simulation of bovine pancreatic trypsin inhibitor (31 kJ mol(-1) difference in the entropy between the first and second part of the simulation). Strictly speaking, this means that it is practically impossible to equilibrate MD simulations of proteins. We discuss the implications of such a lack of strict equilibration of protein MD simulations and show that ligand-binding free energies estimated with the MM/GBSA method (molecular mechanics with generalised Born and surface-area solvation) vary by 3-15 kJ mol(-1) during a 500 ns simulation (the higher estimate is caused by rare conformational changes), although they involve a questionable but well-converged normal-mode entropy estimate, whereas free energies estimated by free-energy perturbation vary by less than 0.6 kJ mol(-1) for the same simulation.

Evaluation of protein-ligand affinity prediction using steered molecular dynamics simulations.

PubMed

Okimoto, Noriaki; Suenaga, Atsushi; Taiji, Makoto

2017-11-01

In computational drug design, ranking a series of compound analogs in a manner that is consistent with experimental affinities remains a challenge. In this study, we evaluated the prediction of protein-ligand binding affinities using steered molecular dynamics simulations. First, we investigated the appropriate conditions for accurate predictions in these simulations. A conic harmonic restraint was applied to the system for efficient sampling of work values on the ligand unbinding pathway. We found that pulling velocity significantly influenced affinity predictions, but that the number of collectable trajectories was less influential. We identified the appropriate pulling velocity and collectable trajectories for binding affinity predictions as 1.25 Å/ns and 100, respectively, and these parameters were used to evaluate three target proteins (FK506 binding protein, trypsin, and cyclin-dependent kinase 2). For these proteins using our parameters, the accuracy of affinity prediction was higher and more stable when Jarzynski's equality was employed compared with the second-order cumulant expansion equation of Jarzynski's equality. Our results showed that steered molecular dynamics simulations are effective for predicting the rank order of ligands; thus, they are a potential tool for compound selection in hit-to-lead and lead optimization processes.

Lipid-converter, a framework for lipid manipulations in molecular dynamics simulations

PubMed Central

Larsson, Per; Kasson, Peter M.

2014-01-01

Construction of lipid membrane and membrane protein systems for molecular dynamics simulations can be a challenging process. In addition, there are few available tools to extend existing studies by repeating simulations using other force fields and lipid compositions. To facilitate this, we introduce lipidconverter, a modular Python framework for exchanging force fields and lipid composition in coordinate files obtained from simulations. Force fields and lipids are specified by simple text files, making it easy to introduce support for additional force fields and lipids. The converter produces simulation input files that can be used for structural relaxation of the new membranes. PMID:25081234

The influence of fatty acids on the GpA dimer interface by coarse-grained molecular dynamics simulation.

PubMed

Flinner, Nadine; Mirus, Oliver; Schleiff, Enrico

2014-08-15

The hydrophobic thickness of membranes, which is manly defined by fatty acids, influences the packing of transmembrane domains of proteins and thus can modulate the activity of these proteins. We analyzed the dynamics of the dimerization of Glycophorin A (GpA) by molecular dynamics simulations to describe the fatty acid dependence of the transmembrane region assembly. GpA represents a well-established model for dimerization of single transmembrane helices containing a GxxxG motif in vitro and in silico. We performed simulations of the dynamics of the NMR-derived dimer as well as self-assembly simulations of monomers in membranes composed of different fatty acid chains and monitored the formed interfaces and their transitions. The observed dimeric interfaces, which also include the one known from NMR, are highly dynamic and converted into each other. The frequency of interface formation and the preferred transitions between interfaces similar to the interface observed by NMR analysis strongly depend on the fatty acid used to build the membrane. Molecular dynamic simulations after adaptation of the helix topology parameters to better represent NMR derived structures of single transmembrane helices yielded an enhanced occurrence of the interface determined by NMR in molecular dynamics simulations. Taken together we give insights into the influence of fatty acids and helix conformation on the dynamics of the transmembrane domain of GpA.

The Influence of Fatty Acids on the GpA Dimer Interface by Coarse-Grained Molecular Dynamics Simulation

PubMed Central

Flinner, Nadine; Mirus, Oliver; Schleiff, Enrico

2014-01-01

The hydrophobic thickness of membranes, which is manly defined by fatty acids, influences the packing of transmembrane domains of proteins and thus can modulate the activity of these proteins. We analyzed the dynamics of the dimerization of Glycophorin A (GpA) by molecular dynamics simulations to describe the fatty acid dependence of the transmembrane region assembly. GpA represents a well-established model for dimerization of single transmembrane helices containing a GxxxG motif in vitro and in silico. We performed simulations of the dynamics of the NMR-derived dimer as well as self-assembly simulations of monomers in membranes composed of different fatty acid chains and monitored the formed interfaces and their transitions. The observed dimeric interfaces, which also include the one known from NMR, are highly dynamic and converted into each other. The frequency of interface formation and the preferred transitions between interfaces similar to the interface observed by NMR analysis strongly depend on the fatty acid used to build the membrane. Molecular dynamic simulations after adaptation of the helix topology parameters to better represent NMR derived structures of single transmembrane helices yielded an enhanced occurrence of the interface determined by NMR in molecular dynamics simulations. Taken together we give insights into the influence of fatty acids and helix conformation on the dynamics of the transmembrane domain of GpA. PMID:25196522

Structure and dynamics of aqueous solutions from PBE-based first-principles molecular dynamics simulations.

PubMed

Pham, Tuan Anh; Ogitsu, Tadashi; Lau, Edmond Y; Schwegler, Eric

2016-10-21

Establishing an accurate and predictive computational framework for the description of complex aqueous solutions is an ongoing challenge for density functional theory based first-principles molecular dynamics (FPMD) simulations. In this context, important advances have been made in recent years, including the development of sophisticated exchange-correlation functionals. On the other hand, simulations based on simple generalized gradient approximation (GGA) functionals remain an active field, particularly in the study of complex aqueous solutions due to a good balance between the accuracy, computational expense, and the applicability to a wide range of systems. Such simulations are often performed at elevated temperatures to artificially "correct" for GGA inaccuracies in the description of liquid water; however, a detailed understanding of how the choice of temperature affects the structure and dynamics of other components, such as solvated ions, is largely unknown. To address this question, we carried out a series of FPMD simulations at temperatures ranging from 300 to 460 K for liquid water and three representative aqueous solutions containing solvated Na + , K + , and Cl - ions. We show that simulations at 390-400 K with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional yield water structure and dynamics in good agreement with experiments at ambient conditions. Simultaneously, this computational setup provides ion solvation structures and ion effects on water dynamics consistent with experiments. Our results suggest that an elevated temperature around 390-400 K with the PBE functional can be used for the description of structural and dynamical properties of liquid water and complex solutions with solvated ions at ambient conditions.

Study of silicon crystal surface formation based on molecular dynamics simulation results

NASA Astrophysics Data System (ADS)

Barinovs, G.; Sabanskis, A.; Muiznieks, A.

2014-04-01

The equilibrium shape of <110>-oriented single crystal silicon nanowire, 8 nm in cross-section, was found from molecular dynamics simulations using LAMMPS molecular dynamics package. The calculated shape agrees well to the shape predicted from experimental observations of nanocavities in silicon crystals. By parametrization of the shape and scaling to a known value of {111} surface energy, Wulff form for solid-vapor interface was obtained. The Wulff form for solid-liquid interface was constructed using the same model of the shape as for the solid-vapor interface. The parameters describing solid-liquid interface shape were found using values of surface energies in low-index directions known from published molecular dynamics simulations. Using an experimental value of the liquid-vapor interface energy for silicon and graphical solution of Herring's equation, we constructed angular diagram showing relative equilibrium orientation of solid-liquid, liquid-vapor and solid-vapor interfaces at the triple phase line. The diagram gives quantitative predictions about growth angles for different growth directions and formation of facets on the solid-liquid and solid-vapor interfaces. The diagram can be used to describe growth ridges appearing on the crystal surface grown from a melt. Qualitative comparison to the ridges of a Float zone silicon crystal cone is given.

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

Clustering effects in ionic polymers: Molecular dynamics simulations

DOE PAGES

Agrawal, Anupriya; Perahia, Dvora; Grest, Gary S.

2015-08-18

Ionic clusters control the structure, dynamics, and transport in soft matter. Incorporating a small fraction of ionizable groups in polymers substantially reduces the mobility of the macromolecules in melts. Furthermore, these ionic groups often associate into random clusters in melts, where the distribution and morphology of the clusters impact the transport in these materials. Here, using molecular dynamic simulations we demonstrate a clear correlation between cluster size and morphology with the polymer mobility in melts of sulfonated polystyrene. We show that in low dielectric media ladderlike clusters that are lower in energy compared with spherical assemblies are formed. Reducing themore » electrostatic interactions by enhancing the dielectric constant leads to morphological transformation from ladderlike clusters to globular assemblies. Finally, decrease in electrostatic interaction significantly enhances the mobility of the polymer.« less

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

PubMed

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

2017-03-28

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

Force-field parametrization and molecular dynamics simulations of Congo red

NASA Astrophysics Data System (ADS)

Król, Marcin; Borowski, Tomasz; Roterman, Irena; Piekarska, Barbara; Stopa, Barbara; Rybarska, Joanna; Konieczny, Leszek

2004-01-01

Congo red, a diazo dye widely used in medical diagnosis, is known to form supramolecular systems in solution. Such a supramolecular system may interact with various proteins. In order to examine the nature of such complexes empirical force field parameters for the Congo red molecule were developed. The parametrization of bonding terms closely followed the methodology used in the development of the charmm22 force field, except for the calculation of charges. Point charges were calculated from a fit to a quantum mechanically derived electrostatic potential using the CHELP-BOW method. Obtained parameters were tested in a series of molecular dynamics simulations of both a single molecule and a micelle composed of Congo red molecules. It is shown that newly developed parameters define a stable minimum on the hypersurface of the potential energy and crystal and ab initio geometries and rotational barriers are well reproduced. Furthermore, rotations around C-N bonds are similar to torsional vibrations observed in crystals of diphenyl-diazene, which confirms that the flexibility of the molecule is correct. Comparison of results obtained from micelles molecular dynamics simulations with experimental data shows that the thermal dependence of micelle creation is well reproduced.

Molecular dynamics simulations on networks of heparin and collagen.

PubMed

Kulke, Martin; Geist, Norman; Friedrichs, Wenke; Langel, Walter

2017-06-01

Synthetic scaffolds containing collagen (Type I) are of increasing interest for bone tissue engineering, especially for highly porous biomaterials in combination with glycosaminoglycans. In experiments the integration of heparin during the fibrillogenesis resulted in different types of collagen fibrils, but models for this aggregation on a molecular scale were only tentative. We conducted molecular dynamic simulations investigating the binding of heparin to collagen and the influence of the telopeptides during collagen aggregation. This aims at explaining experimental findings on a molecular level. Novel structures for N- and C-telopeptides were developed with the TIGER2 replica exchange algorithm and dihedral principle component analysis. We present an extended statistical analysis of the mainly electrostatic interaction between heparin and collagen and identify several binding sites. Finally, we propose a molecular mechanism for the influence of glycosaminoglycans on the morphology of collagen fibrils. Proteins 2017; 85:1119-1130. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Coarse-grained molecular dynamics simulations of polymerization with forward and backward reactions.

PubMed

Krajniak, Jakub; Zhang, Zidan; Pandiyan, Sudharsan; Nies, Eric; Samaey, Giovanni

2018-06-11

We develop novel parallel algorithms that allow molecular dynamics simulations in which byproduct molecules are created and removed because of the chemical reactions during the molecular dynamics simulation. To prevent large increases in the potential energy, we introduce the byproduct molecules smoothly by changing the non-bonded interactions gradually. To simulate complete equilibrium reactions, we allow the byproduct molecules attack and destroy created bonds. Modeling of such reactions are, for instance, important to study the pore formation due to the presence of e.g. water molecules or development of polymer morphology during the process of splitting off byproduct molecules. Another concept that could be studied is the degradation of polymeric materials, a very important topic in a recycling of polymer waste. We illustrate the method by simulating the polymerization of polyethylene terephthalate (PET) at the coarse-grained level as an example of a polycondensation reaction with water as a byproduct. The algorithms are implemented in a publicly available software package and are easily accessible using a domain-specific language that describes chemical reactions in an input configuration file. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

27ps DFT Molecular Dynamics Simulation of a-maltose: A Reduced Basis Set Study.

USDA-ARS?s Scientific Manuscript database

DFT molecular dynamics simulations are time intensive when carried out on carbohydrates such as alpha-maltose, requiring up to three or more weeks on a fast 16-processor computer to obtain just 5ps of constant energy dynamics. In a recent publication [1] forces for dynamics were generated from B3LY...

Cluster growth mechanisms in Lennard-Jones fluids: A comparison between molecular dynamics and Brownian dynamics simulations

NASA Astrophysics Data System (ADS)

Jung, Jiyun; Lee, Jumin; Kim, Jun Soo

2015-03-01

We present a simulation study on the mechanisms of a phase separation in dilute fluids of Lennard-Jones (LJ) particles as a model of self-interacting molecules. Molecular dynamics (MD) and Brownian dynamics (BD) simulations of the LJ fluids are employed to model the condensation of a liquid droplet in the vapor phase and the mesoscopic aggregation in the solution phase, respectively. With emphasis on the cluster growth at late times well beyond the nucleation stage, we find that the growth mechanisms can be qualitatively different: cluster diffusion and coalescence in the MD simulations and Ostwald ripening in the BD simulations. We also show that the rates of the cluster growth have distinct scaling behaviors during cluster growth. This work suggests that in the solution phase the random Brownian nature of the solute dynamics may lead to the Ostwald ripening that is qualitatively different from the cluster coalescence in the vapor phase.

GneimoSim: A Modular Internal Coordinates Molecular Dynamics Simulation Package

PubMed Central

Larsen, Adrien B.; Wagner, Jeffrey R.; Kandel, Saugat; Salomon-Ferrer, Romelia; Vaidehi, Nagarajan; Jain, Abhinandan

2014-01-01

The Generalized Newton Euler Inverse Mass Operator (GNEIMO) method is an advanced method for internal coordinates molecular dynamics (ICMD). GNEIMO includes several theoretical and algorithmic advancements that address longstanding challenges with ICMD simulations. In this paper we describe the GneimoSim ICMD software package that implements the GNEIMO method. We believe that GneimoSim is the first software package to include advanced features such as the equipartition principle derived for internal coordinates, and a method for including the Fixman potential to eliminate systematic statistical biases introduced by the use of hard constraints. Moreover, by design, GneimoSim is extensible and can be easily interfaced with third party force field packages for ICMD simulations. Currently, GneimoSim includes interfaces to LAMMPS, OpenMM, Rosetta force field calculation packages. The availability of a comprehensive Python interface to the underlying C++ classes and their methods provides a powerful and versatile mechanism for users to develop simulation scripts to configure the simulation and control the simulation flow. GneimoSim has been used extensively for studying the dynamics of protein structures, refinement of protein homology models, and for simulating large scale protein conformational changes with enhanced sampling methods. GneimoSim is not limited to proteins and can also be used for the simulation of polymeric materials. PMID:25263538

Heterogeneity in homogeneous nucleation from billion-atom molecular dynamics simulation of solidification of pure metal.

PubMed

Shibuta, Yasushi; Sakane, Shinji; Miyoshi, Eisuke; Okita, Shin; Takaki, Tomohiro; Ohno, Munekazu

2017-04-05

Can completely homogeneous nucleation occur? Large scale molecular dynamics simulations performed on a graphics-processing-unit rich supercomputer can shed light on this long-standing issue. Here, a billion-atom molecular dynamics simulation of homogeneous nucleation from an undercooled iron melt reveals that some satellite-like small grains surrounding previously formed large grains exist in the middle of the nucleation process, which are not distributed uniformly. At the same time, grains with a twin boundary are formed by heterogeneous nucleation from the surface of the previously formed grains. The local heterogeneity in the distribution of grains is caused by the local accumulation of the icosahedral structure in the undercooled melt near the previously formed grains. This insight is mainly attributable to the multi-graphics processing unit parallel computation combined with the rapid progress in high-performance computational environments.Nucleation is a fundamental physical process, however it is a long-standing issue whether completely homogeneous nucleation can occur. Here the authors reveal, via a billion-atom molecular dynamics simulation, that local heterogeneity exists during homogeneous nucleation in an undercooled iron melt.

Network visualization of conformational sampling during molecular dynamics simulation.

PubMed

Ahlstrom, Logan S; Baker, Joseph Lee; Ehrlich, Kent; Campbell, Zachary T; Patel, Sunita; Vorontsov, Ivan I; Tama, Florence; Miyashita, Osamu

2013-11-01

Effective data reduction methods are necessary for uncovering the inherent conformational relationships present in large molecular dynamics (MD) trajectories. Clustering algorithms provide a means to interpret the conformational sampling of molecules during simulation by grouping trajectory snapshots into a few subgroups, or clusters, but the relationships between the individual clusters may not be readily understood. Here we show that network analysis can be used to visualize the dominant conformational states explored during simulation as well as the connectivity between them, providing a more coherent description of conformational space than traditional clustering techniques alone. We compare the results of network visualization against 11 clustering algorithms and principal component conformer plots. Several MD simulations of proteins undergoing different conformational changes demonstrate the effectiveness of networks in reaching functional conclusions. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Molecular dynamics simulations and applications in computational toxicology and nanotoxicology.

PubMed

Selvaraj, Chandrabose; Sakkiah, Sugunadevi; Tong, Weida; Hong, Huixiao

2018-02-01

Nanotoxicology studies toxicity of nanomaterials and has been widely applied in biomedical researches to explore toxicity of various biological systems. Investigating biological systems through in vivo and in vitro methods is expensive and time taking. Therefore, computational toxicology, a multi-discipline field that utilizes computational power and algorithms to examine toxicology of biological systems, has gained attractions to scientists. Molecular dynamics (MD) simulations of biomolecules such as proteins and DNA are popular for understanding of interactions between biological systems and chemicals in computational toxicology. In this paper, we review MD simulation methods, protocol for running MD simulations and their applications in studies of toxicity and nanotechnology. We also briefly summarize some popular software tools for execution of MD simulations. Published by Elsevier Ltd.

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.

Dihedral angle principal component analysis of molecular dynamics simulations.

PubMed

Altis, Alexandros; Nguyen, Phuong H; Hegger, Rainer; Stock, Gerhard

2007-06-28

It has recently been suggested by Mu et al. [Proteins 58, 45 (2005)] to use backbone dihedral angles instead of Cartesian coordinates in a principal component analysis of molecular dynamics simulations. Dihedral angles may be advantageous because internal coordinates naturally provide a correct separation of internal and overall motion, which was found to be essential for the construction and interpretation of the free energy landscape of a biomolecule undergoing large structural rearrangements. To account for the circular statistics of angular variables, a transformation from the space of dihedral angles {phi(n)} to the metric coordinate space {x(n)=cos phi(n),y(n)=sin phi(n)} was employed. To study the validity and the applicability of the approach, in this work the theoretical foundations underlying the dihedral angle principal component analysis (dPCA) are discussed. It is shown that the dPCA amounts to a one-to-one representation of the original angle distribution and that its principal components can readily be characterized by the corresponding conformational changes of the peptide. Furthermore, a complex version of the dPCA is introduced, in which N angular variables naturally lead to N eigenvalues and eigenvectors. Applying the methodology to the construction of the free energy landscape of decaalanine from a 300 ns molecular dynamics simulation, a critical comparison of the various methods is given.

Dihedral angle principal component analysis of molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Altis, Alexandros; Nguyen, Phuong H.; Hegger, Rainer; Stock, Gerhard

2007-06-01

It has recently been suggested by Mu et al. [Proteins 58, 45 (2005)] to use backbone dihedral angles instead of Cartesian coordinates in a principal component analysis of molecular dynamics simulations. Dihedral angles may be advantageous because internal coordinates naturally provide a correct separation of internal and overall motion, which was found to be essential for the construction and interpretation of the free energy landscape of a biomolecule undergoing large structural rearrangements. To account for the circular statistics of angular variables, a transformation from the space of dihedral angles {φn} to the metric coordinate space {xn=cosφn,yn=sinφn} was employed. To study the validity and the applicability of the approach, in this work the theoretical foundations underlying the dihedral angle principal component analysis (dPCA) are discussed. It is shown that the dPCA amounts to a one-to-one representation of the original angle distribution and that its principal components can readily be characterized by the corresponding conformational changes of the peptide. Furthermore, a complex version of the dPCA is introduced, in which N angular variables naturally lead to N eigenvalues and eigenvectors. Applying the methodology to the construction of the free energy landscape of decaalanine from a 300ns molecular dynamics simulation, a critical comparison of the various methods is given.

Molecular Dynamics Simulations of Creatine Kinase and Adenine Nucleotide Translocase in Mitochondrial Membrane Patch*

PubMed Central

Karo, Jaanus; Peterson, Pearu; Vendelin, Marko

2012-01-01

Interaction between mitochondrial creatine kinase (MtCK) and adenine nucleotide translocase (ANT) can play an important role in determining energy transfer pathways in the cell. Although the functional coupling between MtCK and ANT has been demonstrated, the precise mechanism of the coupling is not clear. To study the details of the coupling, we turned to molecular dynamics simulations. We introduce a new coarse-grained molecular dynamics model of a patch of the mitochondrial inner membrane containing a transmembrane ANT and an MtCK above the membrane. The membrane model consists of three major types of lipids (phosphatidylcholine, phosphatidylethanolamine, and cardiolipin) in a roughly 2:1:1 molar ratio. A thermodynamics-based coarse-grained force field, termed MARTINI, has been used together with the GROMACS molecular dynamics package for all simulated systems in this work. Several physical properties of the system are reproduced by the model and are in agreement with known data. This includes membrane thickness, dimension of the proteins, and diffusion constants. We have studied the binding of MtCK to the membrane and demonstrated the effect of cardiolipin on the stabilization of the binding. In addition, our simulations predict which part of the MtCK protein sequence interacts with the membrane. Taken together, the model has been verified by dynamical and structural data and can be used as the basis for further studies. PMID:22241474

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.

Large-scale molecular dynamics simulation of DNA: implementation and validation of the AMBER98 force field in LAMMPS.

PubMed

Grindon, Christina; Harris, Sarah; Evans, Tom; Novik, Keir; Coveney, Peter; Laughton, Charles

2004-07-15

Molecular modelling played a central role in the discovery of the structure of DNA by Watson and Crick. Today, such modelling is done on computers: the more powerful these computers are, the more detailed and extensive can be the study of the dynamics of such biological macromolecules. To fully harness the power of modern massively parallel computers, however, we need to develop and deploy algorithms which can exploit the structure of such hardware. The Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) is a scalable molecular dynamics code including long-range Coulomb interactions, which has been specifically designed to function efficiently on parallel platforms. Here we describe the implementation of the AMBER98 force field in LAMMPS and its validation for molecular dynamics investigations of DNA structure and flexibility against the benchmark of results obtained with the long-established code AMBER6 (Assisted Model Building with Energy Refinement, version 6). Extended molecular dynamics simulations on the hydrated DNA dodecamer d(CTTTTGCAAAAG)(2), which has previously been the subject of extensive dynamical analysis using AMBER6, show that it is possible to obtain excellent agreement in terms of static, dynamic and thermodynamic parameters between AMBER6 and LAMMPS. In comparison with AMBER6, LAMMPS shows greatly improved scalability in massively parallel environments, opening up the possibility of efficient simulations of order-of-magnitude larger systems and/or for order-of-magnitude greater simulation times.

Characterizing dynamic behavior of carbon dioxide nano-jets using molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Huang, Pei-Hsing; Chou, Chuen-Shii; Hung, Shang-Chao; Jhan, Jhih-Wei

2017-12-01

This paper reports on the use of molecular dynamics (MD) simulations to elucidate the dynamic behavior of CO2 through a Graphene/Au(111) nano-injector. We investigated the effects of jet diameter ( d), system temperature ( T), and the extrusion velocity ( v) of a graphite piston plate on the jet pattern, system pressure ( P), and the number of molecules ( N m) in the outflow. Simulation results show that the combined effects of high v and small d induced a larger jet angle, resulting in an increase in the number of CO2 molecules attached to the surface of the outlet. Increasing d enhanced the formation of the T-junction molecular geometry of CO2 molecules, due to the effects of electrostatic attraction between C (0.5888 e) and O (- 0.2944 e) of CO2, which caused the formation of larger agglomerations of CO2 molecules in the vicinity of the nano-injector orifice in the final extrusion stage. The increase in P within the cylinder of the nano-injector was more pronounced during middle and final stages of extrusion, compared with the effects observed during the initial stages. Despite the fact that N m increased noticeably with an increase in T, the value of N m at d = 1.5 nm and T ≥ 300 K greatly exceeded that at d = 1.0 nm and T = 500 K, regardless of the value of v. The numerical simulations presented in this study could be helpful in the design of nano-injectors for a diversity of applications associated with engineering systems and biomedicine at the nano-scale.

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

Next Generation Extended Lagrangian Quantum-based Molecular Dynamics

NASA Astrophysics Data System (ADS)

Negre, Christian

2017-06-01

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

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

Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Kandel, Saugat; Salomon-Ferrer, Romelia; Larsen, Adrien B.; Jain, Abhinandan; Vaidehi, Nagarajan

2016-01-01

The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential

Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations.

PubMed

Kandel, Saugat; Salomon-Ferrer, Romelia; Larsen, Adrien B; Jain, Abhinandan; Vaidehi, Nagarajan

2016-01-28

The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential

Molecular dynamics simulations of thermally activated edge dislocation unpinning from voids in α -Fe

NASA Astrophysics Data System (ADS)

Byggmästar, J.; Granberg, F.; Nordlund, K.

2017-10-01

In this study, thermal unpinning of edge dislocations from voids in α -Fe is investigated by means of molecular dynamics simulations. The activation energy as a function of shear stress and temperature is systematically determined. Simulations with a constant applied stress are compared with dynamic simulations with a constant strain rate. We found that a constant applied stress results in a temperature-dependent activation energy. The temperature dependence is attributed to the elastic softening of iron. If the stress is normalized with the softening of the specific shear modulus, the activation energy is shown to be temperature-independent. From the dynamic simulations, the activation energy as a function of critical shear stress was determined using previously developed methods. The results from the dynamic simulations are in good agreement with the constant stress simulations, after the normalization. This indicates that the computationally more efficient dynamic method can be used to obtain the activation energy as a function of stress and temperature. The obtained relation between stress, temperature, and activation energy can be used to introduce a stochastic unpinning event in larger-scale simulation methods, such as discrete dislocation dynamics.

Design of Supercapacitor Electrodes Using Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Bo, Zheng; Li, Changwen; Yang, Huachao; Ostrikov, Kostya; Yan, Jianhua; Cen, Kefa

2018-06-01

Electric double-layer capacitors (EDLCs) are advanced electrochemical devices for energy storage and have attracted strong interest due to their outstanding properties. Rational optimization of electrode-electrolyte interactions is of vital importance to enhance device performance for practical applications. Molecular dynamics (MD) simulations could provide theoretical guidelines for the optimal design of electrodes and the improvement of capacitive performances, e.g., energy density and power density. Here we discuss recent MD simulation studies on energy storage performance of electrode materials containing porous to nanostructures. The energy storage properties are related to the electrode structures, including electrode geometry and electrode modifications. Altering electrode geometry, i.e., pore size and surface topography, can influence EDL capacitance. We critically examine different types of electrode modifications, such as altering the arrangement of carbon atoms, doping heteroatoms and defects, which can change the quantum capacitance. The enhancement of power density can be achieved by the intensified ion dynamics and shortened ion pathway. Rational control of the electrode morphology helps improve the ion dynamics by decreasing the ion diffusion pathway. Tuning the surface properties (e.g., the affinity between the electrode and the ions) can affect the ion-packing phenomena. Our critical analysis helps enhance the energy and power densities of EDLCs by modulating the corresponding electrode structures and surface properties.[Figure not available: see fulltext.

Multiscale molecular dynamics simulations of membrane remodeling by Bin/Amphiphysin/Rvs family proteins

NASA Astrophysics Data System (ADS)

Chun, Chan; Haohua, Wen; Lanyuan, Lu; Jun, Fan

2016-01-01

Membrane curvature is no longer thought of as a passive property of the membrane; rather, it is considered as an active, regulated state that serves various purposes in the cell such as between cells and organelle definition. While transport is usually mediated by tiny membrane bubbles known as vesicles or membrane tubules, such communication requires complex interplay between the lipid bilayers and cytosolic proteins such as members of the Bin/Amphiphysin/Rvs (BAR) superfamily of proteins. With rapid developments in novel experimental techniques, membrane remodeling has become a rapidly emerging new field in recent years. Molecular dynamics (MD) simulations are important tools for obtaining atomistic information regarding the structural and dynamic aspects of biological systems and for understanding the physics-related aspects. The availability of more sophisticated experimental data poses challenges to the theoretical community for developing novel theoretical and computational techniques that can be used to better interpret the experimental results to obtain further functional insights. In this review, we summarize the general mechanisms underlying membrane remodeling controlled or mediated by proteins. While studies combining experiments and molecular dynamics simulations recall existing mechanistic models, concurrently, they extend the role of different BAR domain proteins during membrane remodeling processes. We review these recent findings, focusing on how multiscale molecular dynamics simulations aid in understanding the physical basis of BAR domain proteins, as a representative of membrane-remodeling proteins. Project supported by the National Natural Science Foundation of China (Grant No. 21403182) and the Research Grants Council of Hong Kong, China (Grant No. CityU 21300014).

Automated chemical kinetic modeling via hybrid reactive molecular dynamics and quantum chemistry simulations.

PubMed

Döntgen, Malte; Schmalz, Felix; Kopp, Wassja A; Kröger, Leif C; Leonhard, Kai

2018-06-13

An automated scheme for obtaining chemical kinetic models from scratch using reactive molecular dynamics and quantum chemistry simulations is presented. This methodology combines the phase space sampling of reactive molecular dynamics with the thermochemistry and kinetics prediction capabilities of quantum mechanics. This scheme provides the NASA polynomial and modified Arrhenius equation parameters for all species and reactions that are observed during the simulation and supplies them in the ChemKin format. The ab initio level of theory for predictions is easily exchangeable and the presently used G3MP2 level of theory is found to reliably reproduce hydrogen and methane oxidation thermochemistry and kinetics data. Chemical kinetic models obtained with this approach are ready-to-use for, e.g., ignition delay time simulations, as shown for hydrogen combustion. The presented extension of the ChemTraYzer approach can be used as a basis for methodologically advancing chemical kinetic modeling schemes and as a black-box approach to generate chemical kinetic models.

Reaching multi-nanosecond timescales in combined QM/MM molecular dynamics simulations through parallel horsetail sampling.

PubMed

Martins-Costa, Marilia T C; Ruiz-López, Manuel F

2017-04-15

We report an enhanced sampling technique that allows to reach the multi-nanosecond timescale in quantum mechanics/molecular mechanics molecular dynamics simulations. The proposed technique, called horsetail sampling, is a specific type of multiple molecular dynamics approach exhibiting high parallel efficiency. It couples a main simulation with a large number of shorter trajectories launched on independent processors at periodic time intervals. The technique is applied to study hydrogen peroxide at the water liquid-vapor interface, a system of considerable atmospheric relevance. A total simulation time of a little more than 6 ns has been attained for a total CPU time of 5.1 years representing only about 20 days of wall-clock time. The discussion of the results highlights the strong influence of the solvation effects at the interface on the structure and the electronic properties of the solute. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Molecular dynamics simulation of the structure and dynamics of 5-HT3 serotonin receptor

NASA Astrophysics Data System (ADS)

Antonov, M. Yu.; Popinako, A. V.; Prokopiev, G. A.

2016-10-01

In this work, we investigated structure, dynamics and ion transportation in transmembrane domain of the 5-HT3 serotonin receptor. High-resolution (0.35 nm) structure of the 5-HT3 receptor in complex with stabilizing nanobodies was determined by protein crystallography in 2014 (Protein data bank (PDB) code 4PIR). Transmembrane domain of the structure was prepared in complex with explicit membrane environment (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC)) and solvent (TIP3P water model). Molecular dynamics protocols for simulation and stabilization of the transmembrane domain of the 5-HT3 receptor model were developed and 60 ns simulation of the structure was conducted in order to explore structural parameters of the system. We estimated the mean force profile for Na+ ions using umbrella sampling method.

Structure and dynamics of aqueous solutions from PBE-based first-principles molecular dynamics simulations

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

Pham, Tuan Anh; Ogitsu, Tadashi; Lau, Edmond Y.

Establishing an accurate and predictive computational framework for the description of complex aqueous solutions is an ongoing challenge for density functional theory based first-principles molecular dynamics (FPMD) simulations. In this context, important advances have been made in recent years, including the development of sophisticated exchange-correlation functionals. On the other hand, simulations based on simple generalized gradient approximation (GGA) functionals remain an active field, particularly in the study of complex aqueous solutions due to a good balance between the accuracy, computational expense, and the applicability to a wide range of systems. In such simulations we often perform them at elevated temperaturesmore » to artificially “correct” for GGA inaccuracies in the description of liquid water; however, a detailed understanding of how the choice of temperature affects the structure and dynamics of other components, such as solvated ions, is largely unknown. In order to address this question, we carried out a series of FPMD simulations at temperatures ranging from 300 to 460 K for liquid water and three representative aqueous solutions containing solvated Na +, K +, and Cl - ions. We show that simulations at 390–400 K with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional yield water structure and dynamics in good agreement with experiments at ambient conditions. Simultaneously, this computational setup provides ion solvation structures and ion effects on water dynamics consistent with experiments. These results suggest that an elevated temperature around 390–400 K with the PBE functional can be used for the description of structural and dynamical properties of liquid water and complex solutions with solvated ions at ambient conditions.« less

Structure and dynamics of aqueous solutions from PBE-based first-principles molecular dynamics simulations

DOE PAGES

Pham, Tuan Anh; Ogitsu, Tadashi; Lau, Edmond Y.; ...

2016-10-17

Establishing an accurate and predictive computational framework for the description of complex aqueous solutions is an ongoing challenge for density functional theory based first-principles molecular dynamics (FPMD) simulations. In this context, important advances have been made in recent years, including the development of sophisticated exchange-correlation functionals. On the other hand, simulations based on simple generalized gradient approximation (GGA) functionals remain an active field, particularly in the study of complex aqueous solutions due to a good balance between the accuracy, computational expense, and the applicability to a wide range of systems. In such simulations we often perform them at elevated temperaturesmore » to artificially “correct” for GGA inaccuracies in the description of liquid water; however, a detailed understanding of how the choice of temperature affects the structure and dynamics of other components, such as solvated ions, is largely unknown. In order to address this question, we carried out a series of FPMD simulations at temperatures ranging from 300 to 460 K for liquid water and three representative aqueous solutions containing solvated Na +, K +, and Cl - ions. We show that simulations at 390–400 K with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional yield water structure and dynamics in good agreement with experiments at ambient conditions. Simultaneously, this computational setup provides ion solvation structures and ion effects on water dynamics consistent with experiments. These results suggest that an elevated temperature around 390–400 K with the PBE functional can be used for the description of structural and dynamical properties of liquid water and complex solutions with solvated ions at ambient conditions.« 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 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.

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.

Protein dynamics in organic media at varying water activity studied by molecular dynamics simulation.

PubMed

Wedberg, Rasmus; Abildskov, Jens; Peters, Günther H

2012-03-01

In nonaqueous enzymology, control of enzyme hydration is commonly approached by fixing the thermodynamic water activity of the medium. In this work, we present a strategy for evaluating the water activity in molecular dynamics simulations of proteins in water/organic solvent mixtures. The method relies on determining the water content of the bulk phase and uses a combination of Kirkwood-Buff theory and free energy calculations to determine corresponding activity coefficients. We apply the method in a molecular dynamics study of Candida antarctica lipase B in pure water and the organic solvents methanol, tert-butyl alcohol, methyl tert-butyl ether, and hexane, each mixture at five different water activities. It is shown that similar water activity yields similar enzyme hydration in the different solvents. However, both solvent and water activity are shown to have profound effects on enzyme structure and flexibility.

Supramolecular Systems Behavior at the Air-Water Interface. Molecular Dynamic Simulation Study.

NASA Astrophysics Data System (ADS)

Sandoval, C.; Saavedra, M.; Gargallo, L.; Radić, D.

2008-08-01

Atomistic molecular dynamics simulation (MDS) was development to investigate the structural and dynamic properties of a monolayer of supramolecular systems. The simulations were performed at room temperature, on inclusion complexes (ICs) of α-cyclodextrin (CD) with poly(ethylene-oxide)(PEO), poly(ɛ-caprolactone)(PEC) and poly(tetrahydrofuran)(PTHF). The simulations were carried out for a surface area of 30Å. The trajectories of the MDS show that the system more stable was IC-PEC, being the less stable IC-PEO. The disordered monolayer for the systems was proved by the orientation correlation function and the radial distribution function between the polar groups of ICs and the water molecules. We found that the system IC-PEC was more stable that the systems IC-PTHF and IC-PEO.

Quantum molecular dynamics simulation of shock-wave experiments in aluminum

NASA Astrophysics Data System (ADS)

Minakov, D. V.; Levashov, P. R.; Khishchenko, K. V.; Fortov, V. E.

2014-06-01

We present quantum molecular dynamics calculations of principal, porous, and double shock Hugoniots, release isentropes, and sound velocity behind the shock front for aluminum. A comprehensive analysis of available shock-wave data is performed; the agreement and discrepancies of simulation results with measurements are discussed. Special attention is paid to the melting region of aluminum along the principal Hugoniot; the boundaries of the melting zone are estimated using the self-diffusion coefficient. Also, we make a comparison with a high-quality multiphase equation of state for aluminum. Independent semiempirical and first-principle models are very close to each other in caloric variables (pressure, density, particle velocity, etc.) but the equation of state gives higher temperature on the principal Hugoniot and release isentropes than ab initio calculations. Thus, the quantum molecular dynamics method can be used for calibration of semiempirical equations of state in case of lack of experimental data.

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

Tensile strength of Iß crystalline cellulose predicted by molecular dynamics simulation

Treesearch

Xiawa Wu; Robert J. Moon; Ashlie Martini

2014-01-01

The mechanical properties of Iß crystalline cellulose are studied using molecular dynamics simulation. A model Iß crystal is deformed in the three orthogonal directions at three different strain rates. The stress-strain behaviors for each case are analyzed and then used to calculate mechanical properties. The results show that the elastic modulus, Poisson's ratio...

Animated molecular dynamics simulations of hydrated caesium-smectite interlayers

PubMed Central

Sutton, Rebecca; Sposito, Garrison

2002-01-01

Computer animation of center of mass coordinates obtained from 800 ps molecular dynamics simulations of Cs-smectite hydrates (1/3 and 2/3 water monolayers) provided information concerning the structure and dynamics of the interlayer region that could not be obtained through traditional simulation analysis methods. Cs+ formed inner sphere complexes with the mineral surface, and could be seen to jump from one attracting location near a layer charge site to the next, while water molecules were observed to migrate from the hydration shell of one ion to that of another. Neighboring ions maintained a partial hydration shell by sharing water molecules, such that a single water molecule hydrated two ions simultaneously for hundreds of picoseconds. Cs-montmorillonite hydrates featured the largest extent of this sharing interaction, because interlayer ions were able to inhabit positions near surface cavities as well as at their edges, close to oxygen triads. The greater positional freedom of Cs+ within the montmorillonite interlayer, a result of structural hydroxyl orientation and low tetrahedral charge, promoted the optimization of distances between cations and water molecules required for water sharing. Preference of Cs+ for locations near oxygen triads was observed within interlayer beidellite and hectorite. Water molecules also could be seen to interact directly with the mineral surface, entering its surface cavities to approach attracting charge sites and structural hydroxyls. With increasing water content, water molecules exhibited increased frequency and duration of both cavity habitation and water sharing interactions. Competition between Cs+ and water molecules for surface sites was evident. These important cooperative and competitive features of interlayer molecular behavior were uniquely revealed by animation of an otherwise highly complex simulation output.

Multiscale simulations of anisotropic particles combining molecular dynamics and Green's function reaction dynamics

NASA Astrophysics Data System (ADS)

Vijaykumar, Adithya; Ouldridge, Thomas E.; ten Wolde, Pieter Rein; Bolhuis, Peter G.

2017-03-01

The modeling of complex reaction-diffusion processes in, for instance, cellular biochemical networks or self-assembling soft matter can be tremendously sped up by employing a multiscale algorithm which combines the mesoscopic Green's Function Reaction Dynamics (GFRD) method with explicit stochastic Brownian, Langevin, or deterministic molecular dynamics to treat reactants at the microscopic scale [A. Vijaykumar, P. G. Bolhuis, and P. R. ten Wolde, J. Chem. Phys. 143, 214102 (2015)]. Here we extend this multiscale MD-GFRD approach to include the orientational dynamics that is crucial to describe the anisotropic interactions often prevalent in biomolecular systems. We present the novel algorithm focusing on Brownian dynamics only, although the methodology is generic. We illustrate the novel algorithm using a simple patchy particle model. After validation of the algorithm, we discuss its performance. The rotational Brownian dynamics MD-GFRD multiscale method will open up the possibility for large scale simulations of protein signalling networks.

Mechanism Responsible for Intercalation of Dimethyl Sulfoxide in Kaolinite: Molecular Dynamics Simulations.

PubMed

Zhang, Shuai; Liu, Qinfu; Cheng, Hongfei; Gao, Feng; Liu, Cun; Teppen, Brian J

2018-01-01

Intercalation is the promising strategy to expand the interlayer region of kaolinite for their further applications. Herein, the adaptive biasing force (ABF) accelerated molecular dynamics simulations were performed to calculate the free energies involved in the kaolinite intercalation by dimethyl sulfoxide (DMSO). Additionally, the classical all atom molecular dynamics simulations were carried out to calculate the interfacial interactions between kaolinite interlayer surfaces and DMSO with the aim at exploring the underlying force that drives the DMSO to enter the interlayer space. The results showed that the favorable interaction of DMSO with both kaolinite interlayer octahedral surface and tetrahedral surface can help in introducing DMSO enter kaolinite interlayer. The hydroxyl groups on octahedral surface functioned as H-donors attracting the S=O groups of DMSO through hydrogen bonding interaction. The tetrahedral surface featuring hydrophobic property attracted the methyl groups of DMSO through hydrophobic interaction. The results provided a detailed picture of the energetics and interlayer structure of kaolinite-DMSO intercalate.

GneimoSim: a modular internal coordinates molecular dynamics simulation package.

PubMed

Larsen, Adrien B; Wagner, Jeffrey R; Kandel, Saugat; Salomon-Ferrer, Romelia; Vaidehi, Nagarajan; Jain, Abhinandan

2014-12-05

The generalized Newton-Euler inverse mass operator (GNEIMO) method is an advanced method for internal coordinates molecular dynamics (ICMD). GNEIMO includes several theoretical and algorithmic advancements that address longstanding challenges with ICMD simulations. In this article, we describe the GneimoSim ICMD software package that implements the GNEIMO method. We believe that GneimoSim is the first software package to include advanced features such as the equipartition principle derived for internal coordinates, and a method for including the Fixman potential to eliminate systematic statistical biases introduced by the use of hard constraints. Moreover, by design, GneimoSim is extensible and can be easily interfaced with third party force field packages for ICMD simulations. Currently, GneimoSim includes interfaces to LAMMPS, OpenMM, and Rosetta force field calculation packages. The availability of a comprehensive Python interface to the underlying C++ classes and their methods provides a powerful and versatile mechanism for users to develop simulation scripts to configure the simulation and control the simulation flow. GneimoSim has been used extensively for studying the dynamics of protein structures, refinement of protein homology models, and for simulating large scale protein conformational changes with enhanced sampling methods. GneimoSim is not limited to proteins and can also be used for the simulation of polymeric materials. © 2014 Wiley Periodicals, Inc.

Charge-Neutral Constant pH Molecular Dynamics Simulations Using a Parsimonious Proton Buffer.

PubMed

Donnini, Serena; Ullmann, R Thomas; Groenhof, Gerrit; Grubmüller, Helmut

2016-03-08

In constant pH molecular dynamics simulations, the protonation states of titratable sites can respond to changes of the pH and of their electrostatic environment. Consequently, the number of protons bound to the biomolecule, and therefore the overall charge of the system, fluctuates during the simulation. To avoid artifacts associated with a non-neutral simulation system, we introduce an approach to maintain neutrality of the simulation box in constant pH molecular dynamics simulations, while maintaining an accurate description of all protonation fluctuations. Specifically, we introduce a proton buffer that, like a buffer in experiment, can exchange protons with the biomolecule enabling its charge to fluctuate. To keep the total charge of the system constant, the uptake and release of protons by the buffer are coupled to the titration of the biomolecule with a constraint. We find that, because the fluctuation of the total charge (number of protons) of a typical biomolecule is much smaller than the number of titratable sites of the biomolecule, the number of buffer sites required to maintain overall charge neutrality without compromising the charge fluctuations of the biomolecule, is typically much smaller than the number of titratable sites, implying markedly enhanced simulation and sampling efficiency.

Molecular dynamics simulations of stratum corneum lipid models: fatty acids and cholesterol.

PubMed

Höltje, M; Förster, T; Brandt, B; Engels, T; von Rybinski, W; Höltje, H D

2001-03-09

We report the results of an investigation on stratum corneum lipids, which present the main barrier of the skin. Molecular dynamics simulations, thermal analysis and FTIR measurements were applied. The primary objective of this work was to study the effect of cholesterol on skin structure and dynamics. Two molecular models were constructed, a free fatty acid bilayer (stearic acid, palmitic acid) and a fatty acid/cholesterol mixture at a 1:1 molar ratio. Our simulations were performed at constant pressure and temperature on a nanosecond time scale. The resulting model structures were characterized by calculating surface areas per headgroup, conformational properties, atom densities and order parameters of the fatty acids. Analysis of the simulations indicates that the free fatty acid fraction of stratum corneum lipids stays in a highly ordered crystalline state at skin temperatures. The phase behavior is strongly influenced when cholesterol is added. Cholesterol smoothes the rigid phases of the fatty acids: the order of the hydrocarbon tails (mainly of the last eight bonds) is reduced, the area per molecule becomes larger, the fraction of trans dihedrals is lower and the hydrophobic thickness is reduced. The simulation results are in good agreement with our experimental data from FTIR analysis and NIR-FT Raman spectroscopy.

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

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.

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

Molecular dynamics simulations of graphoepitaxy of organic semiconductors, sexithiophene, and pentacene: Molecular-scale mechanisms of organic graphoepitaxy

NASA Astrophysics Data System (ADS)

Ikeda, Susumu

2018-03-01

Molecular dynamics (MD) simulations of the organic semiconductors α-sexithiophene (6T) and pentacene were carried out to clarify the mechanism of organic graphoepitaxy at the molecular level. First, the models of the grooved substrates were made and the surfaces of the inside of the grooves were modified with -OH or -OSi(CH3)3, making the surfaces hydrophilic or hydrophobic. By the MD simulations of 6T, it was found that three stable azimuthal directions exist (0, ˜45, and 90° the angle that the c-axis makes with the groove), being consistent with experimental results. MD simulations of deposition processes of 6T and pentacene were also carried out, and pentacene molecules showed the spontaneous formation of herringbone packing during deposition. Some pentacene molecules stood on the surface and formed a cluster whose a-axis was parallel to the groove. It is expected that a deep understanding of the molecular-scale mechanisms will lead graphoepitaxy to practical applications, improving the performance of organic devices.

On the hydration of subnanometric antifouling organosilane adlayers: a molecular dynamics simulation.

PubMed

Sheikh, Sonia; Blaszykowski, Christophe; Nolan, Robert; Thompson, Damien; Thompson, Michael

2015-01-01

The connection between antifouling and surface hydration is a fascinating but daunting question to answer. Herein, we use molecular dynamics (MD) computer simulations to gain further insight into the role of surface functionalities in the molecular-level structuration of water (surface kosmotropicity)--within and atop subnanometric organosilane adlayers that were shown in previous experimental work to display varied antifouling behavior. Our simulations support the hypothesized intimate link between surface hydration and antifouling, in particular the importance of both internal and interfacial hydrophilicity and kosmotropicity. The antifouling mechanism is also discussed in terms of surface dehydration energy and water dynamicity (lability and mobility), notably the crucial requirement for clustered water molecules to remain tightly bound for extensive periods of time--i.e. exhibit slow exchange dynamics. A substrate effect on surface hydration, which would also participate in endowing antifouling adlayers with hydrogel-like characteristics, is also proposed. In contrast, the role of adlayer flexibility, if any, is assigned a secondary role in these ultrathin structures made of short building blocks. The conclusions from this work are well in line with those previously drawn in the literature. Copyright © 2014 Elsevier Inc. All rights reserved.

Concerted Dynamic Motions of an FABP4 Model and Its Ligands Revealed by Microsecond Molecular Dynamics Simulations

PubMed Central

2015-01-01

In this work, we investigate the dynamic motions of fatty acid binding protein 4 (FABP4) in the absence and presence of a ligand by explicitly solvated all-atom molecular dynamics simulations. The dynamics of one ligand-free FABP4 and four ligand-bound FABP4s is compared via multiple 1.2 μs simulations. In our simulations, the protein interconverts between the open and closed states. Ligand-free FABP4 prefers the closed state, whereas ligand binding induces a conformational transition to the open state. Coupled with opening and closing of FABP4, the ligand adopts distinct binding modes, which are identified and compared with crystal structures. The concerted dynamics of protein and ligand suggests that there may exist multiple FABP4–ligand binding conformations. Thus, this work provides details about how ligand binding affects the conformational preference of FABP4 and how ligand binding is coupled with a conformational change of FABP4 at an atomic level. PMID:25231537

Concerted dynamic motions of an FABP4 model and its ligands revealed by microsecond molecular dynamics simulations.

PubMed

Li, Yan; Li, Xiang; Dong, Zigang

2014-10-14

In this work, we investigate the dynamic motions of fatty acid binding protein 4 (FABP4) in the absence and presence of a ligand by explicitly solvated all-atom molecular dynamics simulations. The dynamics of one ligand-free FABP4 and four ligand-bound FABP4s is compared via multiple 1.2 μs simulations. In our simulations, the protein interconverts between the open and closed states. Ligand-free FABP4 prefers the closed state, whereas ligand binding induces a conformational transition to the open state. Coupled with opening and closing of FABP4, the ligand adopts distinct binding modes, which are identified and compared with crystal structures. The concerted dynamics of protein and ligand suggests that there may exist multiple FABP4-ligand binding conformations. Thus, this work provides details about how ligand binding affects the conformational preference of FABP4 and how ligand binding is coupled with a conformational change of FABP4 at an atomic level.

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.

Structure and dynamics of the CrIII ion in aqueous solution: Ab initio QM/MM molecular dynamics simulation.

PubMed

Kritayakornupong, Chinapong; Plankensteiner, Kristof; Rode, Bernd M

2004-10-01

Structural and dynamical properties of the Cr(III) ion in aqueous solution have been investigated using a combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation. The hydration structure of Cr(III) was determined in terms of radial distribution functions, coordination numbers, and angular distributions. The QM/MM simulation gives coordination numbers of 6 and 15.4 for the first and second hydration shell, respectively. The first hydration shell is kinetically very inert but by no means rigid and variations of the first hydration shell geometry lead to distinct splitting in the vibrational spectra of Cr(H(2)O)(6) (3+). A mean residence time of 22 ps was obtained for water ligands residing in the second hydration shell, which is remarkably shorter than the experimentally estimated value. The hydration energy of -1108 +/- 7 kcal/mol, obtained from the QM/MM simulation, corresponds well to the experimental hydration enthalpy value. Copyright 2004 Wiley Periodicals, Inc.

Hybrid molecular-continuum simulations using smoothed dissipative particle dynamics

PubMed Central

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

2015-01-01

We present a new multiscale simulation methodology for coupling a region with atomistic detail simulated via molecular dynamics (MD) to a numerical solution of the fluctuating Navier-Stokes equations obtained from smoothed dissipative particle dynamics (SDPD). In this approach, chemical potential gradients emerge due to differences in resolution within the total system and are reduced by introducing a pairwise thermodynamic force inside the buffer region between the two domains where particles change from MD to SDPD types. When combined with a multi-resolution SDPD approach, such as the one proposed by Kulkarni et al. [J. Chem. Phys. 138, 234105 (2013)], this method makes it possible to systematically couple atomistic models to arbitrarily coarse continuum domains modeled as SDPD fluids with varying resolution. We test this technique by showing that it correctly reproduces thermodynamic properties across the entire simulation domain for a simple Lennard-Jones fluid. Furthermore, we demonstrate that this approach is also suitable for non-equilibrium problems by applying it to simulations of the start up of shear flow. The robustness of the method is illustrated with two different flow scenarios in which shear forces act in directions parallel and perpendicular to the interface separating the continuum and atomistic domains. In both cases, we obtain the correct transient velocity profile. We also perform a triple-scale shear flow simulation where we include two SDPD regions with different resolutions in addition to a MD domain, illustrating the feasibility of a three-scale coupling. PMID:25637963

Structured Ionomer Thin Films at Water Interface: Molecular Dynamics Simulation Insight

DOE PAGES

Aryal, Dipak; Agrawal, Anupriya; Perahia, Dvora; ...

2017-08-23

Controlling the structure and dynamics of thin films of ionizable polymers at water interfaces is critical to their many applications. As the chemical diversity within one polymer is increased, controlling the structure and dynamics of the polymer, which is a key to their use, becomes a challenge. Here molecular dynamics simulations (MD) are used to obtain molecular insight into the structure and dynamics of thin films of one such macromolecule at the interface with water. The polymer consists of an ABCBA topology with randomly sulfonated polystyrene (C), tethered symmetrically to flexible poly(ethylene- r-propylene) blocks (B), and end-capped by a poly(more » t-butylstyrene) block (A). The compositions of the interfacial and bulk regions of thin films of the ABCBA polymers are followed as a function of exposure time to water. We find that interfacial rearrangements take place where buried ionic segments migrate toward the water interface. The hydrophobic blocks collapse and rearrange to minimize their exposure to water. In conclusion, the water that initially drives interfacial reengagements breaks the ionic clusters within the film, forming a dynamic hydrophilic internal network within the hydrophobic segments.« less

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.

Implementation of the force decomposition machine for molecular dynamics simulations.

PubMed

Borštnik, Urban; Miller, Benjamin T; Brooks, Bernard R; Janežič, Dušanka

2012-09-01

We present the design and implementation of the force decomposition machine (FDM), a cluster of personal computers (PCs) that is tailored to running molecular dynamics (MD) simulations using the distributed diagonal force decomposition (DDFD) parallelization method. The cluster interconnect architecture is optimized for the communication pattern of the DDFD method. Our implementation of the FDM relies on standard commodity components even for networking. Although the cluster is meant for DDFD MD simulations, it remains general enough for other parallel computations. An analysis of several MD simulation runs on both the FDM and a standard PC cluster demonstrates that the FDM's interconnect architecture provides a greater performance compared to a more general cluster interconnect. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular Dynamics Simulation of Telomere and TRF1

NASA Astrophysics Data System (ADS)

Kaburagi, Masaaki; Fukuda, Masaki; Yamada, Hironao; Miyakawa, Takeshi; Morikawa, Ryota; Takasu, Masako; Kato, Takamitsu A.; Uesaka, Mitsuru

Telomeres play a central role in determining longevity of a cell. Our study focuses on the interaction between telomeric guanines and TRF1 as a means to observe the telomeric based mechanism of the genome protection. In this research, we performed molecular dynamics simulations of a telomeric DNA and TRF1. Our results show a stable structure with a high affinity for the specific protein. Additionally, we calculated the distance between guanines and the protein in their complex state. From this comparison, we found the calculated values of distance to be very similar, and the angle of guanines in their complex states was larger than that in their single state.

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.

PubMed

Šponer, Jiří; Bussi, Giovanni; Krepl, Miroslav; Banáš, Pavel; Bottaro, Sandro; Cunha, Richard A; Gil-Ley, Alejandro; Pinamonti, Giovanni; Poblete, Simón; Jurečka, Petr; Walter, Nils G; Otyepka, Michal

2018-04-25

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA-ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field.

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

PubMed Central

2018-01-01

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA–ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field. PMID:29297679

Rotational Diffusion Depends on Box Size in Molecular Dynamics Simulations.

PubMed

Linke, Max; Köfinger, Jürgen; Hummer, Gerhard

2018-06-07

We show that the rotational dynamics of proteins and nucleic acids determined from molecular dynamics simulations under periodic boundary conditions suffer from significant finite-size effects. We remove the box-size dependence of the rotational diffusion coefficients by adding a hydrodynamic correction k B T/6 ηV with k B Boltzmann's constant, T the absolute temperature, η the solvent shear viscosity, and V the box volume. We show that this correction accounts for the finite-size dependence of the rotational diffusion coefficients of horse-heart myoglobin and a B-DNA dodecamer in aqueous solution. The resulting hydrodynamic radii are in excellent agreement with experiment.

Mass accommodation of water: bridging the gap between molecular dynamics simulations and kinetic condensation models.

PubMed

Julin, Jan; Shiraiwa, Manabu; Miles, Rachael E H; Reid, Jonathan P; Pöschl, Ulrich; Riipinen, Ilona

2013-01-17

The condensational growth of submicrometer aerosol particles to climate relevant sizes is sensitive to their ability to accommodate vapor molecules, which is described by the mass accommodation coefficient. However, the underlying processes are not yet fully understood. We have simulated the mass accommodation and evaporation processes of water using molecular dynamics, and the results are compared to the condensation equations derived from the kinetic gas theory to shed light on the compatibility of the two. Molecular dynamics simulations were performed for a planar TIP4P-Ew water surface at four temperatures in the range 268-300 K as well as two droplets, with radii of 1.92 and 4.14 nm at T = 273.15 K. The evaporation flux from molecular dynamics was found to be in good qualitative agreement with that predicted by the simple kinetic condensation equations. Water droplet growth was also modeled with the kinetic multilayer model KM-GAP of Shiraiwa et al. [Atmos. Chem. Phys. 2012, 12, 2777]. It was found that, due to the fast transport across the interface, the growth of a pure water droplet is controlled by gas phase diffusion. These facts indicate that the simple kinetic treatment is sufficient in describing pure water condensation and evaporation. The droplet size was found to have minimal effect on the value of the mass accommodation coefficient. The mass accommodation coefficient was found to be unity (within 0.004) for all studied surfaces, which is in agreement with previous simulation work. Additionally, the simulated evaporation fluxes imply that the evaporation coefficient is also unity. Comparing the evaporation rates of the mass accommodation and evaporation simulations indicated that the high collision flux, corresponding to high supersaturation, present in typical molecular dynamics mass accommodation simulations can under certain conditions lead to an increase in the evaporation rate. Consequently, in such situations the mass accommodation coefficient

Mass Accommodation of Water: Bridging the Gap Between Molecular Dynamics Simulations and Kinetic Condensation Models

PubMed Central

2012-01-01

The condensational growth of submicrometer aerosol particles to climate relevant sizes is sensitive to their ability to accommodate vapor molecules, which is described by the mass accommodation coefficient. However, the underlying processes are not yet fully understood. We have simulated the mass accommodation and evaporation processes of water using molecular dynamics, and the results are compared to the condensation equations derived from the kinetic gas theory to shed light on the compatibility of the two. Molecular dynamics simulations were performed for a planar TIP4P-Ew water surface at four temperatures in the range 268–300 K as well as two droplets, with radii of 1.92 and 4.14 nm at T = 273.15 K. The evaporation flux from molecular dynamics was found to be in good qualitative agreement with that predicted by the simple kinetic condensation equations. Water droplet growth was also modeled with the kinetic multilayer model KM-GAP of Shiraiwa et al. [Atmos. Chem. Phys.2012, 117, 2777]. It was found that, due to the fast transport across the interface, the growth of a pure water droplet is controlled by gas phase diffusion. These facts indicate that the simple kinetic treatment is sufficient in describing pure water condensation and evaporation. The droplet size was found to have minimal effect on the value of the mass accommodation coefficient. The mass accommodation coefficient was found to be unity (within 0.004) for all studied surfaces, which is in agreement with previous simulation work. Additionally, the simulated evaporation fluxes imply that the evaporation coefficient is also unity. Comparing the evaporation rates of the mass accommodation and evaporation simulations indicated that the high collision flux, corresponding to high supersaturation, present in typical molecular dynamics mass accommodation simulations can under certain conditions lead to an increase in the evaporation rate. Consequently, in such situations the mass accommodation

Efficiency in nonequilibrium molecular dynamics Monte Carlo simulations

DOE PAGES

Radak, Brian K.; Roux, Benoît

2016-10-07

Hybrid algorithms combining nonequilibrium molecular dynamics and Monte Carlo (neMD/MC) offer a powerful avenue for improving the sampling efficiency of computer simulations of complex systems. These neMD/MC algorithms are also increasingly finding use in applications where conventional approaches are impractical, such as constant-pH simulations with explicit solvent. However, selecting an optimal nonequilibrium protocol for maximum efficiency often represents a non-trivial challenge. This work evaluates the efficiency of a broad class of neMD/MC algorithms and protocols within the theoretical framework of linear response theory. The approximations are validated against constant pH-MD simulations and shown to provide accurate predictions of neMD/MC performance.more » An assessment of a large set of protocols confirms (both theoretically and empirically) that a linear work protocol gives the best neMD/MC performance. Lastly, a well-defined criterion for optimizing the time parameters of the protocol is proposed and demonstrated with an adaptive algorithm that improves the performance on-the-fly with minimal cost.« less

Quantum molecular dynamics simulation of shock-wave experiments in aluminum

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

Minakov, D. V.; Khishchenko, K. V.; Fortov, V. E.

2014-06-14

We present quantum molecular dynamics calculations of principal, porous, and double shock Hugoniots, release isentropes, and sound velocity behind the shock front for aluminum. A comprehensive analysis of available shock-wave data is performed; the agreement and discrepancies of simulation results with measurements are discussed. Special attention is paid to the melting region of aluminum along the principal Hugoniot; the boundaries of the melting zone are estimated using the self-diffusion coefficient. Also, we make a comparison with a high-quality multiphase equation of state for aluminum. Independent semiempirical and first-principle models are very close to each other in caloric variables (pressure, density,more » particle velocity, etc.) but the equation of state gives higher temperature on the principal Hugoniot and release isentropes than ab initio calculations. Thus, the quantum molecular dynamics method can be used for calibration of semiempirical equations of state in case of lack of experimental data.« less

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.

Jdpd: an open java simulation kernel for molecular fragment dissipative particle dynamics.

PubMed

van den Broek, Karina; Kuhn, Hubert; Zielesny, Achim

2018-05-21

Jdpd is an open Java simulation kernel for Molecular Fragment Dissipative Particle Dynamics with parallelizable force calculation, efficient caching options and fast property calculations. It is characterized by an interface and factory-pattern driven design for simple code changes and may help to avoid problems of polyglot programming. Detailed input/output communication, parallelization and process control as well as internal logging capabilities for debugging purposes are supported. The new kernel may be utilized in different simulation environments ranging from flexible scripting solutions up to fully integrated "all-in-one" simulation systems.

Molecular Dynamics Simulations of an Idealized Shock Tube: N2 in Ar Bath Driven by He

NASA Astrophysics Data System (ADS)

Piskulich, Ezekiel Ashe; Sewell, Thomas D.; Thompson, Donald L.

2015-06-01

The dynamics of 10% N2 in Ar initially at 298 K in an idealized shock tube driven by He was studied using molecular dynamics. The simulations were performed using the Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) code. Nitrogen was modeled as a Morse oscillator and non-covalent interactions were approximated by the Buckingham exponential-6 pair potential. The initial pressures in the He driver gas and the driven N2/Ar gas were 1000 atm and 20 atm, respectively. Microcanonical trajectories were followed for 2 ns following release of the driver gas. Results for excitation and subsequent relaxation of the N2, as well as properties of the gas during the simulations, will be reported.

Mapping Conformational Dynamics of Proteins Using Torsional Dynamics Simulations

PubMed Central

Gangupomu, Vamshi K.; Wagner, Jeffrey R.; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-01-01

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein’s experimentally established conformational substates. Conformational transition of calmodulin from the Ca2+-bound to the Ca2+-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

Conformational analysis of oligosaccharides and polysaccharides using molecular dynamics simulations.

PubMed

Frank, Martin

2015-01-01

Complex carbohydrates usually have a large number of rotatable bonds and consequently a large number of theoretically possible conformations can be generated (combinatorial explosion). The application of systematic search methods for conformational analysis of carbohydrates is therefore limited to disaccharides and trisaccharides in a routine analysis. An alternative approach is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD) simulations to explore the conformational space of complex carbohydrates. This chapter describes how to use MD simulation data to perform a conformational analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to build realistic 3D structures of large polysaccharides using Conformational Analysis Tools (CAT).

Thermal conductivity of cross-linked polyethylene from molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Xiong, Xue; Yang, Ming; Liu, Changlin; Li, Xiaobo; Tang, Dawei

2017-07-01

The thermal conductivity of cross-linked bulk polyethylene is studied using molecular dynamics simulation. The atomic structure of the cross-linked polyethylene (PEX) is generated through simulated bond formation using LAMMPS. The thermal conductivity of PEX is studied with different degrees of crosslinking, chain length, and tensile strain. Generally, the thermal conductivity increases with the increasing degree of crosslinking. When the length of the primitive chain increases, the thermal conductivity increases linearly. When the polymer is stretched along one direction, the thermal conductivity increases in the stretched direction and decreases in the direction perpendicular to it. However, the thermal conductivity varies slightly when the polymer is stretched in three directions simultaneously.

Molecular dynamics simulations of glycosyltransferase LgtC.

PubMed

Snajdrová, Lenka; Kulhánek, Petr; Imberty, Anne; Koca, Jaroslav

2004-04-02

Molecular dynamics simulations have been performed on fully solvated alpha-(1-->4)-galactosyltransferase LgtC from Neisseria meningitidis with and without the donor substrate UDP-Gal and in the presence of the manganese ion. The analysis of the trajectories revealed a limited movement in the loop X (residues 75-80) and a larger conformational change in the loop Y (residues 246-251) in the simulation, when UDP-Gal was not present. In this case, the loops X and Y open by almost 10A, exposing the active site to the solvent. The 'hinge region' responsible for the opening is composed of residues 246-247. We have also analyzed the behavior of the manganese ion in the simulations. The coordination number is 6 when UDP-Gal is present and it increases to 7 when it is absent. In the latter case, three water molecules become coordinated to the ion. In both cases, the coordination is very stable implying that the manganese ion is tightly bound in the active site of the enzyme even if UDP-Gal is not present. Further analysis of the structural water molecules location confirmed that the mobility of water molecules in the active site and the accessibility of this site for solvent are higher in the absence of the substrate.

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

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.

Identification of potential herbal inhibitor of acetylcholinesterase associated Alzheimer's disorders using molecular docking and molecular dynamics simulation.

PubMed

Seniya, Chandrabhan; Khan, Ghulam Jilani; Uchadia, Kuldeep

2014-01-01

Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.

Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer's Disorders Using Molecular Docking and Molecular Dynamics Simulation

PubMed Central

Seniya, Chandrabhan; Khan, Ghulam Jilani; Uchadia, Kuldeep

2014-01-01

Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential. PMID:25054066

Applicability of mode-coupling theory to polyisobutylene: a molecular dynamics simulation study.

PubMed

Khairy, Y; Alvarez, F; Arbe, A; Colmenero, J

2013-10-01

The applicability of Mode Coupling Theory (MCT) to the glass-forming polymer polyisobutylene (PIB) has been explored by using fully atomistic molecular dynamics simulations. MCT predictions for the so-called asymptotic regime have been successfully tested on the dynamic structure factor and the self-correlation function of PIB main-chain carbons calculated from the simulated cell. The factorization theorem and the time-temperature superposition principle are satisfied. A consistent fitting procedure of the simulation data to the MCT asymptotic power-laws predicted for the α-relaxation regime has delivered the dynamic exponents of the theory-in particular, the exponent parameter λ-the critical non-ergodicity parameters, and the critical temperature T(c). The obtained values of λ and T(c) agree, within the uncertainties involved in both studies, with those deduced from depolarized light scattering experiments [A. Kisliuk et al., J. Polym. Sci. Part B: Polym. Phys. 38, 2785 (2000)]. Both, λ and T(c)/T(g) values found for PIB are unusually large with respect to those commonly obtained in low molecular weight systems. Moreover, the high T(c)/T(g) value is compatible with a certain correlation of this parameter with the fragility in Angell's classification. Conversely, the value of λ is close to that reported for real polymers, simulated "realistic" polymers and simple polymer models with intramolecular barriers. In the framework of the MCT, such finding should be the signature of two different mechanisms for the glass-transition in real polymers: intermolecular packing and intramolecular barriers combined with chain connectivity.

Molecular Dynamics Simulations of Ion Transport and Mechanisms in Polymer Nanocomposites

NASA Astrophysics Data System (ADS)

Mogurampelly, Santosh; Ganesan, Venkat

2015-03-01

Using all atom molecular dynamics and trajectory-extending kinetic Monte Carlo simulations, we study the influence of Al2O3 nanoparticles on the transport properties of Li+ ions in polymer electrolytes consisting of polyethylene oxide (PEO) melt solvated with LiBF4 salt. We observe that the nanoparticles have a strong influence on polymer segmental dynamics which in turn correlates with the mobility of Li+ ions. Explicitly, polymer segmental relaxation times and Li+ ion residence times around polymer were found to increase with the addition of nanoparticles. We also observe that increasing short range repulsive interactions between nanoparticles and polymer membrane leads to increasing polymer dynamics and ion mobility. Overall, our simulation results suggest that nanoparticle induced changes in conformational and dynamic properties of the polymer influences the ion mobilities in polymer electrolytes and suggests possible directions for using such findings to improve the polymer matrix conductivity. The authors acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin for providing computing resources that have contributed to the research.

Molecular dynamics in principal component space.

PubMed

Michielssens, Servaas; van Erp, Titus S; Kutzner, Carsten; Ceulemans, Arnout; de Groot, Bert L

2012-07-26

A molecular dynamics algorithm in principal component space is presented. It is demonstrated that sampling can be improved without changing the ensemble by assigning masses to the principal components proportional to the inverse square root of the eigenvalues. The setup of the simulation requires no prior knowledge of the system; a short initial MD simulation to extract the eigenvectors and eigenvalues suffices. Independent measures indicated a 6-7 times faster sampling compared to a regular molecular dynamics simulation.

Equilibration of experimentally determined protein structures for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Walton, Emily B.; Vanvliet, Krystyn J.

2006-12-01

Preceding molecular dynamics simulations of biomolecular interactions, the molecule of interest is often equilibrated with respect to an initial configuration. This so-called equilibration stage is required because the input structure is typically not within the equilibrium phase space of the simulation conditions, particularly in systems as complex as proteins, which can lead to artifactual trajectories of protein dynamics. The time at which nonequilibrium effects from the initial configuration are minimized—what we will call the equilibration time—marks the beginning of equilibrium phase-space exploration. Note that the identification of this time does not imply exploration of the entire equilibrium phase space. We have found that current equilibration methodologies contain ambiguities that lead to uncertainty in determining the end of the equilibration stage of the trajectory. This results in equilibration times that are either too long, resulting in wasted computational resources, or too short, resulting in the simulation of molecular trajectories that do not accurately represent the physical system. We outline and demonstrate a protocol for identifying the equilibration time that is based on the physical model of Normal Mode Analysis. We attain the computational efficiency required of large-protein simulations via a stretched exponential approximation that enables an analytically tractable and physically meaningful form of the root-mean-square deviation of atoms comprising the protein. We find that the fitting parameters (which correspond to physical properties of the protein) fluctuate initially but then stabilize for increased simulation time, independently of the simulation duration or sampling frequency. We define the end of the equilibration stage—and thus the equilibration time—as the point in the simulation when these parameters attain constant values. Compared to existing methods, our approach provides the objective identification of the time

Crystal Nucleation in Liquids: Open Questions and Future Challenges in Molecular Dynamics Simulations

PubMed Central

2016-01-01

The nucleation of crystals in liquids is one of nature’s most ubiquitous phenomena, playing an important role in areas such as climate change and the production of drugs. As the early stages of nucleation involve exceedingly small time and length scales, atomistic computer simulations can provide unique insights into the microscopic aspects of crystallization. In this review, we take stock of the numerous molecular dynamics simulations that, in the past few decades, have unraveled crucial aspects of crystal nucleation in liquids. We put into context the theoretical framework of classical nucleation theory and the state-of-the-art computational methods by reviewing simulations of such processes as ice nucleation and the crystallization of molecules in solutions. We shall see that molecular dynamics simulations have provided key insights into diverse nucleation scenarios, ranging from colloidal particles to natural gas hydrates, and that, as a result, the general applicability of classical nucleation theory has been repeatedly called into question. We have attempted to identify the most pressing open questions in the field. We believe that, by improving (i) existing interatomic potentials and (ii) currently available enhanced sampling methods, the community can move toward accurate investigations of realistic systems of practical interest, thus bringing simulations a step closer to experiments. PMID:27228560

Crystal Nucleation in Liquids: Open Questions and Future Challenges in Molecular Dynamics Simulations.

PubMed

Sosso, Gabriele C; Chen, Ji; Cox, Stephen J; Fitzner, Martin; Pedevilla, Philipp; Zen, Andrea; Michaelides, Angelos

2016-06-22

The nucleation of crystals in liquids is one of nature's most ubiquitous phenomena, playing an important role in areas such as climate change and the production of drugs. As the early stages of nucleation involve exceedingly small time and length scales, atomistic computer simulations can provide unique insights into the microscopic aspects of crystallization. In this review, we take stock of the numerous molecular dynamics simulations that, in the past few decades, have unraveled crucial aspects of crystal nucleation in liquids. We put into context the theoretical framework of classical nucleation theory and the state-of-the-art computational methods by reviewing simulations of such processes as ice nucleation and the crystallization of molecules in solutions. We shall see that molecular dynamics simulations have provided key insights into diverse nucleation scenarios, ranging from colloidal particles to natural gas hydrates, and that, as a result, the general applicability of classical nucleation theory has been repeatedly called into question. We have attempted to identify the most pressing open questions in the field. We believe that, by improving (i) existing interatomic potentials and (ii) currently available enhanced sampling methods, the community can move toward accurate investigations of realistic systems of practical interest, thus bringing simulations a step closer to experiments.

Properties of inhibitors of methane hydrate formation via molecular dynamics simulations.

PubMed

Anderson, Brian J; Tester, Jefferson W; Borghi, Gian Paolo; Trout, Bernhardt L

2005-12-21

Within the framework of a proposed two-step mechanism for hydrate inhibition, the energy of binding of four inhibitor molecules (PEO, PVP, PVCap, and VIMA) to a hydrate surface is estimated with molecular dynamic simulations. One key feature of this proposed mechanism is that the binding of an inhibitor molecule to the surface of an ensuing hydrate crystal disrupts growth and therein crystallization. It is found through the molecular dynamic simulations that inhibitor molecules that experimentally exhibit better inhibition strength also have higher free energies of binding, an indirect confirmation of our proposed mechanism. Inhibitors increasing in effectiveness, PEO < PVP < PVCap < VIMA, have increasingly negative (exothermic) binding energies of -0.2 < -20.6 < -37.5 < -45.8 kcal/mol and binding free energies of increasing favorability (+0.4 approximately = +0.5 < -9.4 < -15.1 kcal/mol). Furthermore, the effect of an inhibitor molecule on the local liquid water structure under hydrate-forming conditions was examined and correlated to the experimental effectiveness of the inhibitors. Two molecular characteristics that lead to strongly binding inhibitors were found: (1) a charge distribution on the edge of the inhibitor that mimics the charge separation in the water molecules on the surface of the hydrate and (2) the congruence of the size of the inhibitor with respect to the available space at the hydrate-surface binding site. Equipped with this molecular-level understanding of the process of hydrate inhibition via low-dosage kinetic hydrate inhibitors we can design new, more effective inhibitor molecules.

Dynamics of the EAG1 K+ channel selectivity filter assessed by molecular dynamics simulations.

PubMed

Bernsteiner, Harald; Bründl, Michael; Stary-Weinzinger, Anna

2017-02-26

EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4. Further, ions tended to dissociate away from S0 within less than 20 ns, due to increased filter flexibility. This was followed by water influx from the extracellular side, leading to a widening of the filter in this region, and likely non-conductive filter configurations. Simulations with the inactivation-enhancing mutant Y464A or Na + ions lead to trapped water molecules behind the SF, suggesting that these simulations captured early conformational changes linked to C-type inactivation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The universality of β-hairpin misfolding indicated by molecular dynamics simulations.

PubMed

Shao, Qiang; Wang, Jinan; Shi, Jiye; Zhu, Weiliang

2013-10-28

Previous molecular dynamics simulations showed that besides the experimentally measured folded structures, several β-structured polypeptides could also have misfolded "out-of-register" structures. Through the enhanced sampling molecular dynamics simulations on a series of polypeptides using either implicit or explicit solvent model, the present study systematically investigated the universality of β-hairpin misfolding and its determinants. It was observed that the misfolding could take place for almost all polypeptides under study, especially in the presence of weak side chain hydrophobicity. Moreover, the observed misfolded structures for various polypeptides share the following common features: (1) the turn length in misfolded structure is one-residue shorter than that in folded structure; (2) the hydrophobic side chains on the two strands are pointed to the opposite directions instead of packing in the same direction to form hydrophobic core cluster in the folded structure; and (3) the misfolded structure is one-residue-shifted asymmetric β-hairpin structure. The detailed analysis suggested that the misfolding of β-hairpin is the result of the competition between the formation of the alterable turn configurations and the inter-strand hydrophobic interactions. These predictions are desired to be tested by experiments.

The universality of β-hairpin misfolding indicated by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Shao, Qiang; Wang, Jinan; Shi, Jiye; Zhu, Weiliang

2013-10-01

Previous molecular dynamics simulations showed that besides the experimentally measured folded structures, several β-structured polypeptides could also have misfolded "out-of-register" structures. Through the enhanced sampling molecular dynamics simulations on a series of polypeptides using either implicit or explicit solvent model, the present study systematically investigated the universality of β-hairpin misfolding and its determinants. It was observed that the misfolding could take place for almost all polypeptides under study, especially in the presence of weak side chain hydrophobicity. Moreover, the observed misfolded structures for various polypeptides share the following common features: (1) the turn length in misfolded structure is one-residue shorter than that in folded structure; (2) the hydrophobic side chains on the two strands are pointed to the opposite directions instead of packing in the same direction to form hydrophobic core cluster in the folded structure; and (3) the misfolded structure is one-residue-shifted asymmetric β-hairpin structure. The detailed analysis suggested that the misfolding of β-hairpin is the result of the competition between the formation of the alterable turn configurations and the inter-strand hydrophobic interactions. These predictions are desired to be tested by experiments.

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.

Membrane Sculpting by F-BAR Domains Studied by Molecular Dynamics Simulations

PubMed Central

Yu, Hang; Schulten, Klaus

2013-01-01

Interplay between cellular membranes and their peripheral proteins drives many processes in eukaryotic cells. Proteins of the Bin/Amphiphysin/Rvs (BAR) domain family, in particular, play a role in cellular morphogenesis, for example curving planar membranes into tubular membranes. However, it is still unclear how F-BAR domain proteins act on membranes. Electron microscopy revealed that, in vitro, F-BAR proteins form regular lattices on cylindrically deformed membrane surfaces. Using all-atom and coarse-grained (CG) molecular dynamics simulations, we show that such lattices, indeed, induce tubes of observed radii. A 250 ns all-atom simulation reveals that F-BAR domain curves membranes via the so-called scaffolding mechanism. Plasticity of the F-BAR domain permits conformational change in response to membrane interaction, via partial unwinding of the domains 3-helix bundle structure. A CG simulation covering more than 350 µs provides a dynamic picture of membrane tubulation by lattices of F-BAR domains. A series of CG simulations identified the optimal lattice type for membrane sculpting, which matches closely the lattices seen through cryo-electron microscopy. PMID:23382665

Molecular-dynamics simulations of thin films with a free surface

NASA Astrophysics Data System (ADS)

Peter, Simone; Meyer, Hendrik; Baschnagel, Joerg

2007-03-01

We present results [1,2] from molecular-dynamics simulations for a model of non-entangled short polymer chains in a free standing and a supported film geometry. We investigate the influence of confinement on static and dynamic properties of the melt. We find that the relaxation at the surfaces is faster in comparison to the bulk. We perform a layer-resolved analysis of the dynamics and show that it is possible to associate a gradient in critical temperatures Tc(y) with the gradient in the relaxation dynamics. This finding is in qualitative agreement with experimental results on supported polystyrene (PS) films [Ellison et al, Nat. Mater. 2, 695 (2003)]. Furthermore we show that the y-dependence of Tc(y) can be expressed in terms of the depression of Tc(h), the global Tc for a film of thickness h, if we assume that Tc(h) is the arithmetic mean of Tc(y) and parameterize the depression of Tc(h) by Tc(h)=Tc/(1+h0/h), a formula suggested by Herminghaus et al [Eur. Phys. J E 5, 531 (2001)] for the reduction of the glass transition temperature in supported PS films. We demonstrate the validity of this formula by comparing our simulation results to results from other simulations and experiments. [1] S. Peter, H. Meyer and J. Baschnagel, J. Polym. Sci. B, 44, 2951 (2006) [2] S. Peter, H. Meyer, J. Baschnagel and R, Seemann, J. Phys: Condens. Matter (2007)

Anisotropic Rotational Diffusion Studied by Nuclear Spin Relaxation and Molecular Dynamics Simulation: An Undergraduate Physical Chemistry Laboratory

ERIC Educational Resources Information Center

Fuson, Michael M.

2017-01-01

Laboratories studying the anisotropic rotational diffusion of bromobenzene using nuclear spin relaxation and molecular dynamics simulations are described. For many undergraduates, visualizing molecular motion is challenging. Undergraduates rarely encounter laboratories that directly assess molecular motion, and so the concept remains an…

Investigation of structural dynamics of Thrombocytopenia Cargeeg mutants of human apoptotic cytochrome c: A molecular dynamics simulation approach.

PubMed

Muneeswaran, Gurusamy; Kartheeswaran, Subramanian; Pandiaraj, Manickam; Muthukumar, Kaliappan; Sankaralingam, Muniyandi; Arunachalam, Saravanavadivu

2017-11-01

Naturally occurring mutations to cytochrome c (cyt-c) have been identified recently in patients with mild autosomal dominant thrombocytopenia (low platelet levels), which yield cyt-c mutants with enhanced apoptotic activity. However, the molecular mechanism underlying this low platelet production and enhanced apoptosis remain unclear. Therefore, an attempt is made herein for the first time to investigate the effects of mutations of glycine 41 by serine (G41S) and tyrosine 48 by histidine (Y48H) on the conformational and dynamic changes of apoptotic (Fe 3+ ) cyt-c using all atom molecular dynamics (MD) simulations in explicit water solvent. Our 30ns MD simulations demonstrate considerable structural differences in G41S and Y48H compared to wild type (WT) cyt-c, such as increasing distances between the critical electron transfer residues results in open conformation at the heme active site, large fluctuations in β-turns and α-helices. Additionally, although the β-sheets remain mostly unaffected in all the three cyt-c simulations, the α-helices undergo conformational switch to β-turns in both the mutant simulations. Importantly, this conformational switch of α-helix to β-turn around heme active site should attributes to the loss of intraprotein H-bonds in the mutant simulations especially between NE2 (His26) and O (Pro44) in agreement with the experimental report. Further, essential dynamics analysis reveals that overall motions of WT cyt-c is mainly involved only in the first eigenvector, but in G41S and Y48H the overall motions are mainly in three and two eigenvectors respectively. Overall, the detailed atomistic level information provide a unifying description for the molecular mechanism of structural destabilization, disregulation of platelet formation and enhanced peroxidase activity of the mutant cyt-c's in the pathology of intrinsic apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative characterization of short monomeric polyglutamine peptides by replica exchange molecular dynamics simulation.

PubMed

Nakano, Miki; Watanabe, Hirofumi; Rothstein, Stuart M; Tanaka, Shigenori

2010-05-27

Polyglutamine (polyQ) diseases are caused by an abnormal expansion of CAG repeats. While their detailed structure remains unclear, polyQ peptides assume beta-sheet structures when they aggregate. To investigate the conformational ensemble of short, monomeric polyQ peptides, which consist of 15 glutamine residues (Q(15)), we performed replica exchange molecular dynamics (REMD) simulations. We found that Q(15) can assume multiple configurations due to all of the residues affecting the formation of side-chain hydrogen bonds. Analysis of the free energy landscape reveals that Q(15) has a basin for random-coil structures and another for alpha-helix or beta-turn structures. To investigate properties of aggregated polyQ peptides, we performed multiple molecular dynamics (MMD) simulations for monomeric and oligomeric Q(15). MMD revealed that the formation of oligomers stabilizes the beta-turn structure by increasing the number of hydrogen bonds between the main chains.

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

PubMed

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

2010-12-01

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

Motion Tree Delineates Hierarchical Structure of Protein Dynamics Observed in Molecular Dynamics Simulation

PubMed Central

Moritsugu, Kei; Koike, Ryotaro; Yamada, Kouki; Kato, Hiroaki; Kidera, Akinori

2015-01-01

Molecular dynamics (MD) simulations of proteins provide important information to understand their functional mechanisms, which are, however, likely to be hidden behind their complicated motions with a wide range of spatial and temporal scales. A straightforward and intuitive analysis of protein dynamics observed in MD simulation trajectories is therefore of growing significance with the large increase in both the simulation time and system size. In this study, we propose a novel description of protein motions based on the hierarchical clustering of fluctuations in the inter-atomic distances calculated from an MD trajectory, which constructs a single tree diagram, named a “Motion Tree”, to determine a set of rigid-domain pairs hierarchically along with associated inter-domain fluctuations. The method was first applied to the MD trajectory of substrate-free adenylate kinase to clarify the usefulness of the Motion Tree, which illustrated a clear-cut dynamics picture of the inter-domain motions involving the ATP/AMP lid and the core domain together with the associated amplitudes and correlations. The comparison of two Motion Trees calculated from MD simulations of ligand-free and -bound glutamine binding proteins clarified changes in inherent dynamics upon ligand binding appeared in both large domains and a small loop that stabilized ligand molecule. Another application to a huge protein, a multidrug ATP binding cassette (ABC) transporter, captured significant increases of fluctuations upon binding a drug molecule observed in both large scale inter-subunit motions and a motion localized at a transmembrane helix, which may be a trigger to the subsequent structural change from inward-open to outward-open states to transport the drug molecule. These applications demonstrated the capabilities of Motion Trees to provide an at-a-glance view of various sizes of functional motions inherent in the complicated MD trajectory. PMID:26148295

Thermal- and urea-induced unfolding processes of glutathione S-transferase by molecular dynamics simulation.

PubMed

Li, Jiahuang; Chen, Yuan; Yang, Jie; Hua, Zichun

2015-05-01

The Schistosoma juponicum 26 kDa glutathione S-transferase (sj26GST) consists of the N-terminal domain (N-domain), containing three alpha-helices (named H1-H3) and four anti-parallel beta-strands (S1-S4), and the C-terminal domain (C-domain), comprising five alpha-helices (named H4-H8). In present work, molecular dynamics simulations and fluorescence spectroscopic were used to gain insights into the unfolding process of sj26GST. The molecular dynamics simulations on sj26GST subunit both in water and in 8 M urea were carried out at 300 K, 400 K and 500 K, respectively. Spectroscopic measurements were employed to monitor structural changes. Molecular dynamics simulations of sj26GST subunit induced by urea and temperature showed that the initial unfolding step of sj26GST both in water and urea occurred on N-domain, involving the disruption of helices H2, H3 and strands S3 and S4, whereas H6 was the last region exposed to solution and was the last helix to unfold. Moreover, simulations analyses combining with fluorescence and circular dichroism spectra indicated that N-domain could not fold independent, suggesting that correct folding of N-domain depended on its interactions with C-domain. We further proposed that the folding of GSTs could begin with the hydrophobic collapse of C-domain whose H4, H5, H6 and H7 could move close to each other and form a hydrophobic core, especially H6 wrapped in the hydrophobic center and beginning spontaneous formation of the helix. S3, S4, H3, and H2 could form in the wake of the interaction between C-domain and N-domain. The paper can offer insights into the molecular mechanism of GSTs unfolding. © 2014 Wiley Periodicals, Inc.

Study of the interaction of potassium ion channel protein with micelle by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Shantappa, Anil; Talukdar, Keka

2018-04-01

Ion channels are proteins forming pore inside the body of all living organisms. This potassium ion channel known as KcsA channel and it is found in the each cell and nervous system. Flow of various ions is regulated by the function of the ion channels. The nerve ion channel protein with protein data bank entry 1BL8, which is basically an ion channel protein in Streptomyces Lividans and which is taken up to form micelle-protein system and the system is analyzed by using molecular dynamics simulation. Firstly, ion channel pore is engineered by CHARMM potential and then Micelle-protein system is subjected to molecular dynamics simulation. For some specific micelle concentration, the protein unfolding is observed.

The effect of glycosylation on the transferrin structure: A molecular dynamic simulation analysis.

PubMed

Ghanbari, Z; Housaindokht, M R; Bozorgmehr, M R; Izadyar, M

2016-09-07

Transferrins have been defined by the highly cooperative binding of iron and a carbonate anion to form a Fe-CO3-Tf ternary complex. As such, the layout of the binding site residues affects transferrin function significantly; In contrast to N-lobe, C-lobe binding site of the transferrin structure has been less characterized and little research which surveyed the interaction of carbonate with transferrin in the C-lobe binding site has been found. In the present work, molecular dynamic simulation was employed to gain access into the molecular level understanding of carbonate binding site and their interactions in each lobe. Residues responsible for carbonate binding of transferrin structure were pointed out. In addition, native human transferrin is a glycoprotein that two N-linked complex glycan chains located in the C-lobe. Usually, in the molecular dynamic simulation for simplifying, glycan is removed from the protein structure. Here, we explore the effect of glycosylation on the transferrin structure. Glycosylation appears to have an effect on the layout of the binding site residue and transferrin structure. On the other hand, sometimes the entire transferrin formed by separated lobes that it allows the results to be interpreted in a straightforward manner rather than more parameters required for full length protein. But, it should be noted that there are differences between the separated lobe and full length transferrin, hence, a comparative analysis by the molecular dynamic simulation was performed to investigate such structural variations. Results revealed that separation in C-lobe caused a significant structural variation in comparison to N-lobe. Consequently, the separated lobes and the full length one are different, showing the importance of the interlobe communication and the impact of the lobes on each other in the transferrin structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Dynamics Simulations of G Protein-Coupled Receptors.

PubMed

Bruno, Agostino; Costantino, Gabriele

2012-04-01

G protein-coupled receptors (GPCRs) constitute the largest family of membrane-bound receptors with more than 800 members encoded by 351 genes in humans. It has been estimated that more than 50 % of clinically available drugs act on GPCRs, with an amount of 400, 50 and 25 druggable proteins for the class A, B and C, respectively. Furthermore, Class A GPCRs with approximately 25 % of marketed small drugs represent the most attractive pharmaceutical class. The recent availability of high-resolution 3-dimensional structures of some GPCRs supports the notion that GPCRs are dynamically versatile, and their functions can be modulated by several factors. In this scenario, molecular dynamics (MD) simulations techniques appear to be crucial when studying GPCR flexibility associated to functioning and ligand recognition. A general overview of biased and unbiased MD techniques is here presented with special emphasis on the recent results obtained in the GPCRs field. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Parameterization of Ca+2-protein interactions for molecular dynamics simulations.

PubMed

Project, Elad; Nachliel, Esther; Gutman, Menachem

2008-05-01

Molecular dynamics simulations of Ca+2 ions near protein were performed with three force fields: GROMOS96, OPLS-AA, and CHARMM22. The simulations reveal major, force-field dependent, inconsistencies in the interaction between the Ca+2 ions with the protein. The variations are attributed to the nonbonded parameterizations of the Ca+2-carboxylates interactions. The simulations results were compared to experimental data, using the Ca+2-HCOO- equilibrium as a model. The OPLS-AA force field grossly overestimates the binding affinity of the Ca+2 ions to the carboxylate whereas the GROMOS96 and CHARMM22 force fields underestimate the stability of the complex. Optimization of the Lennard-Jones parameters for the Ca+2-carboxylate interactions were carried out, yielding new parameters which reproduce experimental data. Copyright 2007 Wiley Periodicals, Inc.

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

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.

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

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).

Molecular dynamics simulations on interaction between bacterial proteins: Implication on pathogenic activities.

PubMed

Mondal, Manas; Chakrabarti, Jaydeb; Ghosh, Mahua

2018-03-01

We perform molecular dynamics simulation studies on interaction between bacterial proteins: an outer-membrane protein STY3179 and a yfdX protein STY3178 of Salmonella Typhi. STY3179 has been found to be involved in bacterial adhesion and invasion. STY3178 is recently biophysically characterized. It is a soluble protein having antibiotic binding and chaperon activity capabilities. These two proteins co-occur and are from neighboring gene in Salmonella Typhi-occurrence of homologs of both STY3178 and STY3179 are identified in many Gram-negative bacteria. We show using homology modeling, docking followed by molecular dynamics simulation that they can form a stable complex. STY3178 belongs to aqueous phase, while the beta barrel portion of STY3179 remains buried in DPPC bilayer with extra-cellular loops exposed to water. To understand the molecular basis of interaction between STY3178 and STY3179, we compute the conformational thermodynamics which indicate that these two proteins interact through polar and acidic residues belonging to their interfacial region. Conformational thermodynamics results further reveal instability of certain residues in extra-cellular loops of STY3179 upon complexation with STY3178 which is an indication for binding with host cell protein laminin. © 2017 Wiley Periodicals, Inc.

An investigation of molecular dynamics simulation and molecular docking: interaction of citrus flavonoids and bovine β-lactoglobulin in focus.

PubMed

Sahihi, M; Ghayeb, Y

2014-08-01

Citrus flavonoids are natural compounds with important health benefits. The study of their interaction with a transport protein, such as bovine β-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to investigate the interaction of hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as transport protein. The molecular docking results revealed that these flavonoids bind in the internal cavity of BLG and the BLG affinity for binding the flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking results also indicated that the BLG-flavonoid complexes are stabilized through hydrophobic interactions, hydrogen bond interactions and π-π stacking interactions. The analysis of molecular dynamics (MD) simulation trajectories showed that the root mean square deviation (RMSD) of various systems reaches equilibrium and fluctuates around the mean value at various times. Time evolution of the radius of gyration, total solvent accessible surface of the protein and the second structure of protein showed as well that BLG and BLG-flavonoid complexes were stable around 2500ps, and there was not any conformational change as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations indicated the rigidity of the ligand binding site during the simulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mapping conformational dynamics of proteins using torsional dynamics simulations.

PubMed

Gangupomu, Vamshi K; Wagner, Jeffrey R; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-05-07

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein's experimentally established conformational substates. Conformational transition of calmodulin from the Ca(2+)-bound to the Ca(2+)-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

Molecular dynamics simulations reveal the conformational dynamics of Arabidopsis thaliana BRI1 and BAK1 receptor-like kinases.

PubMed

Moffett, Alexander S; Bender, Kyle W; Huber, Steven C; Shukla, Diwakar

2017-07-28

The structural motifs responsible for activation and regulation of eukaryotic protein kinases in animals have been studied extensively in recent years, and a coherent picture of their activation mechanisms has begun to emerge. In contrast, non-animal eukaryotic protein kinases are not as well understood from a structural perspective, representing a large knowledge gap. To this end, we investigated the conformational dynamics of two key Arabidopsis thaliana receptor-like kinases, brassinosteroid-insensitive 1 (BRI1) and BRI1-associated kinase 1 (BAK1), through extensive molecular dynamics simulations of their fully phosphorylated kinase domains. Molecular dynamics simulations calculate the motion of each atom in a protein based on classical approximations of interatomic forces, giving researchers insight into protein function at unparalleled spatial and temporal resolutions. We found that in an otherwise "active" BAK1 the αC helix is highly disordered, a hallmark of deactivation, whereas the BRI1 αC helix is moderately disordered and displays swinging behavior similar to numerous animal kinases. An analysis of all known sequences in the A. thaliana kinome found that αC helix disorder may be a common feature of plant kinases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

i-PI: A Python interface for ab initio path integral molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Ceriotti, Michele; More, Joshua; Manolopoulos, David E.

2014-03-01

Recent developments in path integral methodology have significantly reduced the computational expense of including quantum mechanical effects in the nuclear motion in ab initio molecular dynamics simulations. However, the implementation of these developments requires a considerable programming effort, which has hindered their adoption. Here we describe i-PI, an interface written in Python that has been designed to minimise the effort required to bring state-of-the-art path integral techniques to an electronic structure program. While it is best suited to first principles calculations and path integral molecular dynamics, i-PI can also be used to perform classical molecular dynamics simulations, and can just as easily be interfaced with an empirical forcefield code. To give just one example of the many potential applications of the interface, we use it in conjunction with the CP2K electronic structure package to showcase the importance of nuclear quantum effects in high-pressure water. Catalogue identifier: AERN_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AERN_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 138626 No. of bytes in distributed program, including test data, etc.: 3128618 Distribution format: tar.gz Programming language: Python. Computer: Multiple architectures. Operating system: Linux, Mac OSX, Windows. RAM: Less than 256 Mb Classification: 7.7. External routines: NumPy Nature of problem: Bringing the latest developments in the modelling of nuclear quantum effects with path integral molecular dynamics to ab initio electronic structure programs with minimal implementational effort. Solution method: State-of-the-art path integral molecular dynamics techniques are implemented in a Python interface. Any electronic structure code can be patched to receive the atomic

Molecular dynamics simulation of Bu4N+ in dimethylformamide: Solvation-induced volume changes

NASA Astrophysics Data System (ADS)

Kiselev, M. G.; Safonova, L. P.

2011-06-01

The structure of the Bu4N+-dimethylformamide system in the condensed and gas phases was studied by molecular dynamics simulation and quantum-chemical calculations. The calculation results were used to reveal the role played by steric effects in the volumetric characteristics of ion solvation.

Solvation and Dynamics of Sodium and Potassium in Ethylene Carbonate from ab Initio Molecular Dynamics Simulations

DOE PAGES

Pham, Tuan Anh; Kweon, Kyoung E.; Samanta, Amit; ...

2017-09-18

The development of sodium and potassium batteries offers a promising way to meet the scaling and cost challenges of energy storage. However, compared to Li +, several intrinsic properties of Na + and K +, including their solvation and dynamics in typical organic electrolytes utilized in battery applications, are less well-understood. Here in this paper, we report a systematic investigation of Na + and K + in ethylene carbonate (EC) using first-principles molecular dynamics simulations. Our simulations reveal significant differences in the solvation structure and dynamical properties of Na + and K + compared to Li +. We find that,more » in contrast to Li + which exhibits a well-defined first solvation shell, the larger Na+ and K+ ions show more disordered and flexible solvation structures. These differences in solvation were found to significantly influence the ion dynamics, leading to larger diffusion coefficients of Na + and K + compared to Li +. Our simulations also reveal a clear and interesting analog in the behavior of the ions in EC and aqueous environments, particularly in the specific ion effects on the solvent dynamics. Lastly, this work provides fundamental understanding of the intrinsic properties of Na + and K + in organic electrolytes, which may ultimately influence the intercalation mechanism at the electrode–electrolyte interface and therefore battery performance, lifetime, and safety.« less

Insights into structural and dynamical features of water at halloysite interfaces probed by DFT and classical molecular dynamics simulations.

PubMed

Presti, Davide; Pedone, Alfonso; Mancini, Giordano; Duce, Celia; Tiné, Maria Rosaria; Barone, Vincenzo

2016-01-21

Density functional theory calculations and classical molecular dynamics simulations have been used to investigate the structure and dynamics of water molecules on kaolinite surfaces and confined in the interlayer of a halloysite model of nanometric dimension. The first technique allowed us to accurately describe the structure of the tetrahedral-octahedral slab of kaolinite in vacuum and in interaction with water molecules and to assess the performance of two widely employed empirical force fields to model water/clay interfaces. Classical molecular dynamics simulations were used to study the hydrogen bond network structure and dynamics of water adsorbed on kaolinite surfaces and confined in the halloysite interlayer. The results are in nice agreement with the few experimental data available in the literature, showing a pronounced ordering and reduced mobility of water molecules at the hydrophilic octahedral surfaces of kaolinite and confined in the halloysite interlayer, with respect to water interacting with the hydrophobic tetrahedral surfaces and in the bulk. Finally, this investigation provides new atomistic insights into the structural and dynamical properties of water-clay interfaces, which are of fundamental importance for both natural processes and industrial applications.

Molecular dynamics simulations of field emission from a planar nanodiode

NASA Astrophysics Data System (ADS)

Torfason, Kristinn; Valfells, Agust; Manolescu, Andrei

2015-03-01

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

A model for including thermal conduction in molecular dynamics simulations

NASA Technical Reports Server (NTRS)

Wu, Yue; Friauf, Robert J.

1989-01-01

A technique is introduced for including thermal conduction in molecular dynamics simulations for solids. A model is developed to allow energy flow between the computational cell and the bulk of the solid when periodic boundary conditions cannot be used. Thermal conduction is achieved by scaling the velocities of atoms in a transitional boundary layer. The scaling factor is obtained from the thermal diffusivity, and the results show good agreement with the solution for a continuous medium at long times. The effects of different temperature and size of the system, and of variations in strength parameter, atomic mass, and thermal diffusivity were investigated. In all cases, no significant change in simulation results has been found.

Ergodicity and model quality in template-restrained canonical and temperature/Hamiltonian replica exchange coarse-grained molecular dynamics simulations of proteins.

PubMed

Karczyńska, Agnieszka S; Czaplewski, Cezary; Krupa, Paweł; Mozolewska, Magdalena A; Joo, Keehyoung; Lee, Jooyoung; Liwo, Adam

2017-12-05

Molecular simulations restrained to single or multiple templates are commonly used in protein-structure modeling. However, the restraints introduce additional barriers, thus impairing the ergodicity of simulations, which can affect the quality of the resulting models. In this work, the effect of restraint types and simulation schemes on ergodicity and model quality was investigated by performing template-restrained canonical molecular dynamics (MD), multiplexed replica-exchange molecular dynamics, and Hamiltonian replica exchange molecular dynamics (HREMD) simulations with the coarse-grained UNRES force field on nine selected proteins, with pseudo-harmonic log-Gaussian (unbounded) or Lorentzian (bounded) restraint functions. The best ergodicity was exhibited by HREMD. It has been found that non-ergodicity does not affect model quality if good templates are used to generate restraints. However, when poor-quality restraints not covering the entire protein are used, the improved ergodicity of HREMD can lead to significantly improved protein models. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Molecular Dynamics Simulation of Membranes and a Transmembrane Helix

NASA Astrophysics Data System (ADS)

Duong, Tap Ha; Mehler, Ernest L.; Weinstein, Harel

1999-05-01

Three molecular dynamics (MD) simulations of 1.5-ns length were carried out on fully hydrated patches of dimyristoyl phosphatidylcholine (DMPC) bilayers in the liquid-crystalline phase. The simulations were performed using different ensembles and electrostatic conditions: a microcanonical ensemble or constant pressure-temperature ensemble, with or without truncated electrostatic interactions. Calculated properties of the membrane patches from the three different protocols were compared to available data from experiments. These data include the resulting overall geometrical dimensions, the order characteristics of the lipid hydrocarbon chains, as well as various measures of the conformations of the polar head groups. The comparisons indicate that the simulation carried out within the microcanonical ensemble with truncated electrostatic interactions yielded results closest to the experimental data, provided that the initial equilibration phase preceding the production run was sufficiently long. The effects of embedding a non-ideal helical protein domain in the membrane patch were studied with the same MD protocols. This simulation was carried out for 2.5 ns. The protein domain corresponds to the seventh transmembrane segment (TMS7) of the human serotonin 5HT 2Areceptor. The peptide is composed of two α-helical segments linked by a hinge domain around a perturbing Asn-Pro motif that produces at the end of the simulation a kink angle of nearly 80° between the two helices. Several aspects of the TMS7 structure, such as the bending angle, backbone Φ and Ψ torsion angles, the intramolecular hydrogen bonds, and the overall conformation, were found to be very similar to those determined by NMR for the corresponding transmembrane segment of the tachykinin NK-1 receptor. In general, the simulations were found to yield structural and dynamic characteristics that are in good agreement with experiment. These findings support the application of simulation methods to the study

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.

Metascalable molecular dynamics simulation of nano-mechano-chemistry

NASA Astrophysics Data System (ADS)

Shimojo, F.; Kalia, R. K.; Nakano, A.; Nomura, K.; Vashishta, P.

2008-07-01

We have developed a metascalable (or 'design once, scale on new architectures') parallel application-development framework for first-principles based simulations of nano-mechano-chemical processes on emerging petaflops architectures based on spatiotemporal data locality principles. The framework consists of (1) an embedded divide-and-conquer (EDC) algorithmic framework based on spatial locality to design linear-scaling algorithms, (2) a space-time-ensemble parallel (STEP) approach based on temporal locality to predict long-time dynamics, and (3) a tunable hierarchical cellular decomposition (HCD) parallelization framework to map these scalable algorithms onto hardware. The EDC-STEP-HCD framework exposes and expresses maximal concurrency and data locality, thereby achieving parallel efficiency as high as 0.99 for 1.59-billion-atom reactive force field molecular dynamics (MD) and 17.7-million-atom (1.56 trillion electronic degrees of freedom) quantum mechanical (QM) MD in the framework of the density functional theory (DFT) on adaptive multigrids, in addition to 201-billion-atom nonreactive MD, on 196 608 IBM BlueGene/L processors. We have also used the framework for automated execution of adaptive hybrid DFT/MD simulation on a grid of six supercomputers in the US and Japan, in which the number of processors changed dynamically on demand and tasks were migrated according to unexpected faults. The paper presents the application of the framework to the study of nanoenergetic materials: (1) combustion of an Al/Fe2O3 thermite and (2) shock initiation and reactive nanojets at a void in an energetic crystal.

Absorption and folding of melittin onto lipid bilayer membranes via unbiased atomic detail microsecond molecular dynamics simulation.

PubMed

Chen, Charles H; Wiedman, Gregory; Khan, Ayesha; Ulmschneider, Martin B

2014-09-01

Unbiased molecular simulation is a powerful tool to study the atomic details driving functional structural changes or folding pathways of highly fluid systems, which present great challenges experimentally. Here we apply unbiased long-timescale molecular dynamics simulation to study the ab initio folding and partitioning of melittin, a template amphiphilic membrane active peptide. The simulations reveal that the peptide binds strongly to the lipid bilayer in an unstructured configuration. Interfacial folding results in a localized bilayer deformation. Akin to purely hydrophobic transmembrane segments the surface bound native helical conformer is highly resistant against thermal denaturation. Circular dichroism spectroscopy experiments confirm the strong binding and thermostability of the peptide. The study highlights the utility of molecular dynamics simulations for studying transient mechanisms in fluid lipid bilayer systems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014. Published by Elsevier B.V.

Information flow and protein dynamics: the interplay between nuclear magnetic resonance spectroscopy and molecular dynamics simulations

PubMed Central

Pastor, Nina; Amero, Carlos

2015-01-01

Proteins participate in information pathways in cells, both as links in the chain of signals, and as the ultimate effectors. Upon ligand binding, proteins undergo conformation and motion changes, which can be sensed by the following link in the chain of information. Nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations represent powerful tools for examining the time-dependent function of biological molecules. The recent advances in NMR and the availability of faster computers have opened the door to more detailed analyses of structure, dynamics, and interactions. Here we briefly describe the recent applications that allow NMR spectroscopy and MD simulations to offer unique insight into the basic motions that underlie information transfer within and between cells. PMID:25999971

Elucidating the mechanism of protein water channels by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Grubmuller, Helmut

2004-03-01

Aquaporins are highly selective water channels. Molecular dynamics simulations of multiple water permeation events correctly predict the measured rate and explain at the atomic level why these membrane channels are so efficient, while blocking other small molecules, ions, and even protons. High efficiency is achieved through a carefully tailored balance of hydrogen bonds that the protein substitutes for the bulk interactions; selectivity is achieved mainly by electrostatic barriers.

Molecular dynamics simulations of field emission from a prolate spheroidal tip

NASA Astrophysics Data System (ADS)

Torfason, Kristinn; Valfells, Agust; Manolescu, Andrei

2016-12-01

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

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

PubMed Central

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

2012-01-01

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

Molecular dynamics simulations of fluoropolymers in the solid state

NASA Astrophysics Data System (ADS)

Holt, David Bryan

1998-10-01

Molecular mechanics and dynamics simulations have been utilized to address the behavior of helix reversal defects in fluoropolymers. The results of the simulations confirm that helix reversals do form and migrate in PTFE crystals. The most important defect structure is a helix reversal band: two helix reversals which bracker a small chain segment (typically 6-7 backbone atoms) having the opposite helical sense from the parent molecule. Small reversal bands had velocities ranging between 100 m/s (low temperature)-250 m/s (high temperature). The size of this reversal band defect is dependent upon the helical conformation and is equal to approximately half of the helical repeat unit in the low and intermediate temperature phases. In the high temperature phase where intermolecular effects are diminished, a wider distribution of reversal band sizes was observed during the simulations. A mechanism is identified by which significant reorientation of a chain segment about the molecular axis can occur when it is bracketed by two helix reversal bands. Simulations with a model containing a perfluoromethyl (PFM) group at low temperature showed that the presence of the PFM group significantly restricts chain mobility locally. However, a significant reduction in the helix reversal defect density was observed on neighboring chains as well. During simulations in which a shear deformation was applied to the models with and without a PFM group, an increase in reversal defect density was observed. However, the helix reversal density in the sheared model containing the PFM branch was less than that in the model without a PFM branch under no shear. These data implicate helix reversal defects and associated chain segment motions in the mechanical behavior of fluoropolymer materials.

A Molecular Dynamics Simulation of the Turbulent Couette Minimal Flow Unit

NASA Astrophysics Data System (ADS)

Smith, Edward

2016-11-01

What happens to turbulent motions below the Kolmogorov length scale? In order to explore this question, a 300 million molecule Molecular Dynamics (MD) simulation is presented for the minimal Couette channel in which turbulence can be sustained. The regeneration cycle and turbulent statistics show excellent agreement to continuum based computational fluid dynamics (CFD) at Re=400. As MD requires only Newton's laws and a form of inter-molecular potential, it captures a much greater range of phenomena without requiring the assumptions of Newton's law of viscosity, thermodynamic equilibrium, fluid isotropy or the limitation of grid resolution. The fundamental nature of MD means it is uniquely placed to explore the nature of turbulent transport. A number of unique insights from MD are presented, including energy budgets, sub-grid turbulent energy spectra, probability density functions, Lagrangian statistics and fluid wall interactions. EPSRC Post Doctoral Prize Fellowship.

Analyzing the Molecular Kinetics of Water Spreading on Hydrophobic Surfaces via Molecular Dynamics Simulation.

PubMed

Zhao, Lei; Cheng, Jiangtao

2017-09-07

In this paper, we report molecular kinetic analyses of water spreading on hydrophobic surfaces via molecular dynamics simulation. The hydrophobic surfaces are composed of amorphous polytetrafluoroethylene (PTFE) with a static contact angle of ~112.4° for water. On the basis of the molecular kinetic theory (MKT), the influences of both viscous damping and solid-liquid retarding were analyzed in evaluating contact line friction, which characterizes the frictional force on the contact line. The unit displacement length on PTFE was estimated to be ~0.621 nm and is ~4 times as long as the bond length of C-C backbone. The static friction coefficient was found to be ~[Formula: see text] Pa·s, which is on the same order of magnitude as the dynamic viscosity of water, and increases with the droplet size. A nondimensional number defined by the ratio of the standard deviation of wetting velocity to the characteristic wetting velocity was put forward to signify the strength of the inherent contact line fluctuation and unveil the mechanism of enhanced energy dissipation in nanoscale, whereas such effect would become insignificant in macroscale. Moreover, regarding a liquid droplet on hydrophobic or superhydrophobic surfaces, an approximate solution to the base radius development was derived by an asymptotic expansion approach.

Multipole Algorithms for Molecular Dynamics Simulation on High Performance Computers.

NASA Astrophysics Data System (ADS)

Elliott, William Dewey

1995-01-01

A fundamental problem in modeling large molecular systems with molecular dynamics (MD) simulations is the underlying N-body problem of computing the interactions between all pairs of N atoms. The simplest algorithm to compute pair-wise atomic interactions scales in runtime {cal O}(N^2), making it impractical for interesting biomolecular systems, which can contain millions of atoms. Recently, several algorithms have become available that solve the N-body problem by computing the effects of all pair-wise interactions while scaling in runtime less than {cal O}(N^2). One algorithm, which scales {cal O}(N) for a uniform distribution of particles, is called the Greengard-Rokhlin Fast Multipole Algorithm (FMA). This work describes an FMA-like algorithm called the Molecular Dynamics Multipole Algorithm (MDMA). The algorithm contains several features that are new to N-body algorithms. MDMA uses new, efficient series expansion equations to compute general 1/r^{n } potentials to arbitrary accuracy. In particular, the 1/r Coulomb potential and the 1/r^6 portion of the Lennard-Jones potential are implemented. The new equations are based on multivariate Taylor series expansions. In addition, MDMA uses a cell-to-cell interaction region of cells that is closely tied to worst case error bounds. The worst case error bounds for MDMA are derived in this work also. These bounds apply to other multipole algorithms as well. Several implementation enhancements are described which apply to MDMA as well as other N-body algorithms such as FMA and tree codes. The mathematics of the cell -to-cell interactions are converted to the Fourier domain for reduced operation count and faster computation. A relative indexing scheme was devised to locate cells in the interaction region which allows efficient pre-computation of redundant information and prestorage of much of the cell-to-cell interaction. Also, MDMA was integrated into the MD program SIgMA to demonstrate the performance of the program over

Ligand Induced Conformational Changes of the Human Serotonin Transporter Revealed by Molecular Dynamics Simulations

PubMed Central

Grouleff, Julie; Schiøtt, Birgit

2013-01-01

The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design. PMID:23776432

Short-Range Order and Collective Dynamics of DMPC Bilayers: A Comparison between Molecular Dynamics Simulations, X-Ray, and Neutron Scattering Experiments

PubMed Central

Hub, Jochen S.; Salditt, Tim; Rheinstädter, Maikel C.; de Groot, Bert L.

2007-01-01

We present an extensive comparison of short-range order and short wavelength dynamics of a hydrated phospholipid bilayer derived by molecular dynamics simulations, elastic x-ray, and inelastic neutron scattering experiments. The quantities that are compared between simulation and experiment include static and dynamic structure factors, reciprocal space mappings, and electron density profiles. We show that the simultaneous use of molecular dynamics and diffraction data can help to extract real space properties like the area per lipid and the lipid chain ordering from experimental data. In addition, we assert that the interchain distance can be computed to high accuracy from the interchain correlation peak of the structure factor. Moreover, it is found that the position of the interchain correlation peak is not affected by the area per lipid, while its correlation length decreases linearly with the area per lipid. This finding allows us to relate a property of the structure factor quantitatively to the area per lipid. Finally, the short wavelength dynamics obtained from the simulations and from inelastic neutron scattering are analyzed and compared. The conventional interpretation in terms of the three-effective-eigenmode model is found to be only partly suitable to describe the complex fluid dynamics of lipid chains. PMID:17631531

Lightweight computational steering of very large scale molecular dynamics simulations

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

Beazley, D.M.; Lomdahl, P.S.

1996-09-01

We present a computational steering approach for controlling, analyzing, and visualizing very large scale molecular dynamics simulations involving tens to hundreds of millions of atoms. Our approach relies on extensible scripting languages and an easy to use tool for building extensions and modules. The system is extremely easy to modify, works with existing C code, is memory efficient, and can be used from inexpensive workstations and networks. We demonstrate how we have used this system to manipulate data from production MD simulations involving as many as 104 million atoms running on the CM-5 and Cray T3D. We also show howmore » this approach can be used to build systems that integrate common scripting languages (including Tcl/Tk, Perl, and Python), simulation code, user extensions, and commercial data analysis packages.« less

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

Biological evaluation, docking and molecular dynamic simulation of some novel diaryl urea derivatives bearing quinoxalindione moiety

PubMed Central

Sadeghian-Rizi, Sedighe; Khodarahmi, Ghadamali Ali; Sakhteman, Amirhossein; Jahanian-Najafabadi, Ali; Rostami, Mahboubeh; Mirzaei, Mahmoud; Hassanzadeh, Farshid

2017-01-01

In this study a series of diarylurea derivatives containing quinoxalindione group were biologically evaluated for their cytotoxic activities using MTT assay against MCF-7 and HepG2 cell lines. Antibacterial activities of these compounds were also evaluated by Microplate Alamar Blue Assay (MABA) against three Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three Gram-positive (Staphylococcus aureus, Bacillus subtilis and Listeria monocitogenes) and one yeast-like fungus (Candida albicans) strain. Furthermore, molecular docking was carried out to study the binding pattern of the compounds to the active site of B-RAF kinase (PDB code: 1UWH). Molecular dynamics simulation was performed on the best ligand (16e) to investigate the ligand binding dynamics in the physiological environment. Cytotoxic evaluation revealed the most prominent cytotoxicity for 6 compounds with IC50 values of 10-18 μM against two mentioned cell lines. None of the synthesized compounds showed significant antimicrobial activity. The obtained results of the molecular docking study showed that all compounds fitted in the binding site of enzyme with binding energy range of -11.22 to -12.69 kcal/mol vs sorafenib binding energy -11.74 kcal/mol as the lead compound. Molecular dynamic simulation indicated that the binding of ligand (16e) was stable in the active site of B-RAF during the simulation. PMID:29204178

Molecular dynamics simulations of amphiphilic graft copolymer molecules at a water/air interface.

PubMed

Anderson, Philip M; Wilson, Mark R

2004-11-01

Fully atomistic molecular dynamics simulations of amphiphilic graft copolymer molecules have been performed at a range of surface concentrations at a water/air interface. These simulations are compared to experimental results from a corresponding system over a similar range of surface concentrations. Neutron reflectivity data calculated from the simulation trajectories agrees well with experimentally acquired profiles. In particular, excellent agreement in neutron reflectivity is found for lower surface concentration simulations. A simulation of a poly(ethylene oxide) (PEO) chain in aqueous solution has also been performed. This simulation allows the conformational behavior of the free PEO chain and those tethered to the interface in the previous simulations to be compared. (c) 2004 American Institute of Physics.

Molecular dynamics simulation of water at mineral surfaces: Structure, dynamics, energetics and hydrogen bonding

NASA Astrophysics Data System (ADS)

Kalinichev, A. G.; Wang, J.; Kirkpatrick, R.

2006-05-01

Fundamental molecular-level understanding of the properties of aqueous mineral interfaces is of great importance for many geochemical and environmental systems. Interaction between water and mineral surfaces substantially affects the properties of both phases, including the reactivity and functionality of the substrate surface, and the structure, dynamics, and energetics of the near surface aqueous phase. Experimental studies of interfacial water structure and dynamics using surface-sensitive techniques such as sum-frequency vibrational spectroscopy or X-ray and neutron reflectivity are not always possible for many practically important substrates, and their results often require interpretation concerning the atomistic mechanisms responsible for the observed behavior. Molecular computer simulations can provide new insight into the underlying molecular- level relationships between the inorganic substrate structure and composition and the structure, ordering, and dynamics of interfacial water. We have performed a series of molecular dynamics (MD) computer simulations of aqueous interfaces with several silicates (quartz, muscovite, and talc) and hydroxides (brucite, portlandite, gibbsite, Ca/Al and Mg/Al double hydroxides) to quantify the effects of the substrate mineral structure and composition on the structural, transport, and thermodynamic properties of water on these mineral surfaces. Due to the prevalent effects of the development of well-interconnected H-bonding networks across the mineral- water interfaces, all the hydroxide surfaces (including a fully hydroxylated quartz surface) show very similar H2O density profiles perpendicular to the interface. However, the predominant orientations of the interfacial H2O molecules and their detailed 2-dimensional near-surface structure and dynamics parallel to the interface are quite different reflecting the differences in the substrate structural charge distribution and the density and orientations of the surface OH

Nanoscale deicing by molecular dynamics simulation.

PubMed

Xiao, Senbo; He, Jianying; Zhang, Zhiliang

2016-08-14

Deicing is important to human activities in low-temperature circumstances, and is critical for combating the damage caused by excessive accumulation of ice. The aim of creating anti-icing materials, surfaces and applications relies on the understanding of fundamental nanoscale ice adhesion mechanics. Here in this study, we employ all-atom modeling and molecular dynamics simulation to investigate ice adhesion. We apply force to detach and shear nano-sized ice cubes for probing the determinants of atomistic adhesion mechanics, and at the same time investigate the mechanical effect of a sandwiched aqueous water layer between ice and substrates. We observe that high interfacial energy restricts ice mobility and increases both ice detaching and shearing stresses. We quantify up to a 60% decrease in ice adhesion strength by an aqueous water layer, and provide atomistic details that support previous experimental studies. Our results contribute quantitative comparison of nanoscale adhesion strength of ice on hydrophobic and hydrophilic surfaces, and supply for the first time theoretical references for understanding the mechanics at the atomistic origins of macroscale ice adhesion.

Molecular dynamics simulation of square graphene-nanoflake oscillator on graphene nanoribbon.

PubMed

Kang, Jeong Won; Lee, Kang Whan

2014-12-01

Graphene nanoflakes (GNFs) have been of interest for a building block in order to develop electromechanical devices on a nanometer scale. Here, we present the oscillation motions of a square GNF oscillator on graphene nanoribbon (GNR) in the retracting-motions by performing classical molecular dynamics simulations. The simulation results showed that the GNF oscillators can be considered as a building block for nanoelectromechanical systems such as carbon-nanotube (CNT) oscillators. The oscillation dynamics of the GNF oscillator were similar to those of the CNT oscillators. When the square GNF had an initial velocity as impulse dynamics, its oscillation motions on the GNR were achieved from its self-retracting van der Waals force. For low initial velocity, its translational motions were dominant in its motions rather than its rotational motions. The kinetic energy damping ratio rapidly decreased as initial velocity increased and the kinetic energy for the translational motion of the GNF oscillator rapidly transferred into that for its rotational motion. The oscillation frequency of the GNF oscillator was dependent on its initial velocity.

Classical molecular dynamics simulation of electronically non-adiabatic processes.

PubMed

Miller, William H; Cotton, Stephen J

2016-12-22

Both classical and quantum mechanics (as well as hybrids thereof, i.e., semiclassical approaches) find widespread use in simulating dynamical processes in molecular systems. For large chemical systems, however, which involve potential energy surfaces (PES) of general/arbitrary form, it is usually the case that only classical molecular dynamics (MD) approaches are feasible, and their use is thus ubiquitous nowadays, at least for chemical processes involving dynamics on a single PES (i.e., within a single Born-Oppenheimer electronic state). This paper reviews recent developments in an approach which extends standard classical MD methods to the treatment of electronically non-adiabatic processes, i.e., those that involve transitions between different electronic states. The approach treats nuclear and electronic degrees of freedom (DOF) equivalently (i.e., by classical mechanics, thereby retaining the simplicity of standard MD), and provides "quantization" of the electronic states through a symmetrical quasi-classical (SQC) windowing model. The approach is seen to be capable of treating extreme regimes of strong and weak coupling between the electronic states, as well as accurately describing coherence effects in the electronic DOF (including the de-coherence of such effects caused by coupling to the nuclear DOF). A survey of recent applications is presented to illustrate the performance of the approach. Also described is a newly developed variation on the original SQC model (found universally superior to the original) and a general extension of the SQC model to obtain the full electronic density matrix (at no additional cost/complexity).

Exploration of the chlorpyrifos escape pathway from acylpeptide hydrolases using steered molecular dynamics simulations.

PubMed

Wang, Dongmei; Jin, Hanyong; Wang, Junling; Guan, Shanshan; Zhang, Zuoming; Han, Weiwei

2016-01-01

Acylpeptide hydrolases (APH) catalyze the removal of an N-acylated amino acid from blocked peptides. APH is significantly more sensitive than acetylcholinesterase, a target of Alzheimer's disease, to inhibition by organophosphorus (OP) compounds. Thus, OP compounds can be used as a tool to probe the physiological functions of APH. Here, we report the results of a computational study of molecular dynamics simulations of APH bound to the OP compounds and an exploration of the chlorpyrifos escape pathway using steered molecular dynamics (SMD) simulations. In addition, we apply SMD simulations to identify potential escape routes of chlorpyrifos from hydrolase hydrophobic cavities in the APH-inhibitor complex. Two previously proposed APH pathways were reliably identified by CAVER 3.0, with the estimated relative importance of P1 > P2 for its size. We identify the major pathway, P2, using SMD simulations, and Arg526, Glu88, Gly86, and Asn65 are identified as important residues for the ligand leaving via P2. These results may help in the design of APH-targeting drugs with improved efficacy, as well as in understanding APH selectivity of the inhibitor binding in the prolyl oligopeptidase family.

Structure and Dynamics of Confined C-O-H Fluids Relevant to the Subsurface: Application of Magnetic Resonance, Neutron Scattering and Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Gautam, Siddharth S.; Ok, Salim; Cole, David R.

2017-06-01

Geo-fluids consisting of C-O-H volatiles are the main mode of transport of mass and energy throughout the lithosphere and are commonly found confined in pores, grain boundaries and fractures. The confinement of these fluids by porous media at the length scales of a few nanometers gives rise to numerous physical and chemical properties that deviate from the bulk behavior. Studying the structural and dynamical properties of these confined fluids at the length and time scales of nanometers and picoseconds respectively forms an important component of understanding their behavior. To study confined fluids, non-destructive penetrative probes are needed. Nuclear magnetic resonance (NMR) by virtue of its ability to monitor longitudinal and transverse magnetization relaxations of spins, and chemical shifts brought about by the chemical environment of a nucleus, and measuring diffusion coefficient provides a good opportunity to study dynamics and chemical structure at the molecular length and time scales. Another technique that gives insights into the dynamics and structure at these length and time scales is neutron scattering (NS). This is because the wavelength and energies of cold and thermal neutrons used in scattering experiments are in the same range as the spatial features and energies involved in the dynamical processes occurring at the molecular level. Molecular Dynamics (MD) simulations on the other hand help with the interpretation of the NMR and NS data. Simulations can also supplement the experiments by calculating quantities not easily accessible to experiments. Thus using NMR, NS and MD simulations in conjunction, a complete description of the molecular structure and dynamics of confined geo-fluids can be obtained. In the current review, our aim is to show how a synergistic use of these three techniques has helped shed light on the complex behavior of water, CO2, and low molecular weight hydrocarbons. After summarizing the theoretical backgrounds of the

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.

Free-energy analyses of a proton transfer reaction by simulated-tempering umbrella sampling and first-principles molecular dynamics simulations.

PubMed

Mori, Yoshiharu; Okamoto, Yuko

2013-02-01

A simulated tempering method, which is referred to as simulated-tempering umbrella sampling, for calculating the free energy of chemical reactions is proposed. First principles molecular dynamics simulations with this simulated tempering were performed to study the intramolecular proton transfer reaction of malonaldehyde in an aqueous solution. Conformational sampling in reaction coordinate space can be easily enhanced with this method, and the free energy along a reaction coordinate can be calculated accurately. Moreover, the simulated-tempering umbrella sampling provides trajectory data more efficiently than the conventional umbrella sampling method.

Molecular dynamics simulations of field emission from a planar nanodiode

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

Torfason, Kristinn; Valfells, Agust; Manolescu, Andrei

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

Molecular Dynamics Analysis of Lysozyme Protein in Ethanol- Water Mixed Solvent

DTIC Science & Technology

2012-01-01

molecular dynamics simulations of solvent effect on lysozyme protein, using water, ethanol, and different concentrations of water-ethanol mixtures as...understood. This work focuses on detailed molecular dynamics simulations of solvent effect on lysozyme protein, using water, ethanol, and different...using GROMACS molecular dynamics simulation (MD) code. Compared to water environment, the lysozyme structure showed remarkable changes in water

Application of principal component analysis in protein unfolding: an all-atom molecular dynamics simulation study.

PubMed

Das, Atanu; Mukhopadhyay, Chaitali

2007-10-28

We have performed molecular dynamics (MD) simulation of the thermal denaturation of one protein and one peptide-ubiquitin and melittin. To identify the correlation in dynamics among various secondary structural fragments and also the individual contribution of different residues towards thermal unfolding, principal component analysis method was applied in order to give a new insight to protein dynamics by analyzing the contribution of coefficients of principal components. The cross-correlation matrix obtained from MD simulation trajectory provided important information regarding the anisotropy of backbone dynamics that leads to unfolding. Unfolding of ubiquitin was found to be a three-state process, while that of melittin, though smaller and mostly helical, is more complicated.

Application of principal component analysis in protein unfolding: An all-atom molecular dynamics simulation study