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MD Simulations (md + simulation)
Selected AbstractsAn Atomistic MD Simulation and Pair-Distribution-Function Study of Disorder and Reactivity of ,-AlF3 Nanoparticles.CHEMINFORM, Issue 3 2007Santanu Chaudhuri Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Chemical Crosslinking of PVA and Prediction of Material Properties by Means of Fully Atomistic MD SimulationsMACROMOLECULAR THEORY AND SIMULATIONS, Issue 4-5 2009Javier Sacristan Bermejo Abstract A method has been developed for building fully atomistic models of chemically crosslinked PVA. It combines a dynamic crosslinking approach followed by a high-temperature annealing procedure. The crosslinking procedure allows to control both crosslinking density and the amount of free crosslinking sites. It also takes into account some network defects, such as dangling tails and wasted loops, which have been experimentally observed on chemically crosslinked polymer networks. This procedure is applied to PVA which is chemically crosslinked with two different linear polyols. Several material properties such as glass transition temperature, Young's, shear and bulk modulus were predicted from the equilibrated structures and found to agree well with available experimental data. [source] Dependency of Tritium Retention in Graphite on Temperature Control of Molecular DynamicsCONTRIBUTIONS TO PLASMA PHYSICS, Issue 3-5 2010A. Ito Abstract We have investigated the carbon plasma facing material and hydrogen atom interaction by the use of molecular dynamics simulation to clarify chemical erosion processes on divertor plate. The present paper is our first try at elucidation of temperature dependence by the molecular dynamics. Temperature was controlled by using Langevin thermostat method. As a result, the retention of hydrogen atom achieve steady state, and the CH4 was generated, which was not found MD simulations without a temperature control method. About 30 percent of injected hydrogen atoms are retained. CH4 yields has a peak at 600 K, which accords with experimental results. A dominant path of CH4 generation found by the present molecular dynamics simulation is as follows: a CH is detached from eroded surface and then it grows into CH4 adsorbing hydrogen atoms via CH2 and CH3. In addition, we propose the problem that the hydrogen atom retention and CH,, yields depend on the thermal relaxation time in MD simulation using temperature control methods (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Protein folding simulations: From coarse-grained model to all-atom modelIUBMB LIFE, Issue 6 2009Jian Zhang Abstract Protein folding is an important and challenging problem in molecular biology. During the last two decades, molecular dynamics (MD) simulation has proved to be a paramount tool and was widely used to study protein structures, folding kinetics and thermodynamics, and structure,stability,function relationship. It was also used to help engineering and designing new proteins, and to answer even more general questions such as the minimal number of amino acid or the evolution principle of protein families. Nowadays, the MD simulation is still undergoing rapid developments. The first trend is to toward developing new coarse-grained models and studying larger and more complex molecular systems such as protein,protein complex and their assembling process, amyloid related aggregations, and structure and motion of chaperons, motors, channels and virus capsides; the second trend is toward building high resolution models and explore more detailed and accurate pictures of protein folding and the associated processes, such as the coordination bond or disulfide bond involved folding, the polarization, charge transfer and protonate/deprotonate process involved in metal coupled folding, and the ion permeation and its coupling with the kinetics of channels. On these new territories, MD simulations have given many promising results and will continue to offer exciting views. Here, we review several new subjects investigated by using MD simulations as well as the corresponding developments of appropriate protein models. These include but are not limited to the attempt to go beyond the topology based G,-like model and characterize the energetic factors in protein structures and dynamics, the study of the thermodynamics and kinetics of disulfide bond involved protein folding, the modeling of the interactions between chaperonin and the encapsulated protein and the protein folding under this circumstance, the effort to clarify the important yet still elusive folding mechanism of protein BBL, the development of discrete MD and its application in studying the ,,, conformational conversion and oligomer assembling process, and the modeling of metal ion involved protein folding. © 2009 IUBMB IUBMB Life, 61(6): 627,643, 2009 [source] Reconstruction of atomistic details from coarse-grained structuresJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2010Andrzej J. Rzepiela Abstract We present an algorithm to reconstruct atomistic structures from their corresponding coarse-grained (CG) representations and its implementation into the freely available molecular dynamics (MD) program package GROMACS. The central part of the algorithm is a simulated annealing MD simulation in which the CG and atomistic structures are coupled via restraints. A number of examples demonstrate the application of the reconstruction procedure to obtain low-energy atomistic structural ensembles from their CG counterparts. We reconstructed individual molecules in vacuo (NCQ tripeptide, dipalmitoylphosphatidylcholine, and cholesterol), bulk water, and a WALP transmembrane peptide embedded in a solvated lipid bilayer. The first examples serve to optimize the parameters for the reconstruction procedure, whereas the latter examples illustrate the applicability to condensed-phase biomolecular systems. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source] Coarse-grained force field for the nucleosome from self-consistent multiscalingJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 9 2008Karine Voltz Abstract A coarse-grained simulation model for the nucleosome is developed, using a methodology modified from previous work on the ribosome. Protein residues and DNA nucleotides are represented as beads, interacting through harmonic (for neighboring) or Morse (for nonbonded) potentials. Force-field parameters were estimated by Boltzmann inversion of the corresponding radial distribution functions obtained from a 5-ns all-atom molecular dynamics (MD) simulation, and were refined to produce agreement with the all-atom MD simulation. This self-consistent multiscale approach yields a coarse-grained model that is capable of reproducing equilibrium structural properties calculated from a 50-ns all-atom MD simulation. This coarse-grained model speeds up nucleosome simulations by a factor of 103 and is expected to be useful in examining biologically relevant dynamical nucleosome phenomena on the microsecond timescale and beyond. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Molecular dynamics simulation in the grand canonical ensembleJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 10 2007Hossein Eslami Abstract An extended system Hamiltonian is proposed to perform molecular dynamics (MD) simulation in the grand canonical ensemble. The Hamiltonian is similar to the one proposed by Lynch and Pettitt (Lynch and Pettitt, J Chem Phys 1997, 107, 8594), which consists of the kinetic and potential energies for real and fractional particles as well as the kinetic and potential energy terms for material and heat reservoirs interacting with the system. We perform a nonlinear scaling of the potential energy parameters of the fractional particle, as well as its mass to vary the number of particles dynamically. On the basis of the equations of motion derived from this Hamiltonian, an algorithm has been proposed for MD simulation at constant chemical potential. The algorithm has been tested for the ideal gas, for the Lennard,Jones fluid over a wide range of temperatures and densities, and for water. The results for the low-density Lennard,Jones fluid are compared with the predictions from a truncated virial equation of state. In the case of the dense Lennard,Jones fluid and water our predicted results are compared with the results reported using other available methods for the calculation of the chemical potential. The method is also applied to the case of vapor-liquid coexistence point predictions. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [source] Molecular dynamics simulation of clustered DNA damage sites containing 8-oxoguanine and abasic siteJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 8 2005Hirofumi Fujimoto Abstract Clustered DNA damage sites induced by ionizing radiation have been suggested to have serious consequences to organisms, such as cancer, due to their reduced probability to be repaired by the enzymatic repair machinery of the cell. Although experimental results have revealed that clustered DNA damage sites effectively retard the efficient function of repair enzymes, it remains unclear as to what particular factors influence this retardation. In this study, approaches based on molecular dynamics (MD) simulation have been applied to examine conformational changes and energetic properties of DNA molecules containing clustered damage sites consisting of two lesioned sites, namely 7,8-dihydro-8-oxoguanine (8-oxoG) and apurinic/apyrimidinic (AP) site, located within a few base pairs of each other. After 1 ns of MD simulation, one of the six DNA molecules containing a clustered damage site develops specific characteristic features: sharp bending at the lesioned site and weakening or complete loss of electrostatic interaction energy between 8-oxoG and bases located on the complementary strand. From these results it is suggested that these changes would make it difficult for the repair enzyme to bind to the lesions within the clustered damage site and thereby result in a reduction of its repair capacity. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 788,798, 2005 [source] Rigid-body dynamics in the isothermal-isobaric ensemble: A test on the accuracy and computational efficiencyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 8 2003Wataru Shinoda Abstract We have developed a time-reversible rigid-body (rRB) molecular dynamics algorithm in the isothermal-isobaric (NPT) ensemble. The algorithm is an extension of rigid-body dynamics [Matubayasi and Nakahara, J Chem Phys 1999, 110, 3291] to the NPT ensemble on the basis of non-Hamiltonian statistical mechanics [Martyna, G. J. et al., J Chem Phys 1994, 101, 4177]. A series of MD simulations of water as well as fully hydrated lipid bilayer systems have been undertaken to investigate the accuracy and efficiency of the algorithm. The rRB algorithm was shown to be superior to the state-of-the-art constraint-dynamics algorithm SHAKE/RATTLE/ROLL, with respect to computational efficiency. However, it was revealed that both algorithms produced accurate trajectories of molecules in the NPT as well as NVT ensembles, as long as a reasonably short time step was used. A couple of multiple time-step (MTS) integration schemes were also examined. The advantage of the rRB algorithm for computational efficiency increased when the MD simulation was carried out using MTS on parallel processing computer systems; total computer time for MTS-MD of a lipid bilayer using 64 processors was reduced by about 40% using rRB instead of SHAKE/RATTLE/ROLL. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 920,930, 2003 [source] Peptide T exhibits a well-defined structure in fluorinated solvent at low temperatureJOURNAL OF PEPTIDE SCIENCE, Issue 12 2009Tran-Chin Yang Abstract The structure of Peptide T was determined by solution NMR spectroscopy, under strong structure-inducing conditions: 40% hexafluoro-2-propanol aqueous solution at 5 °C. Under these conditions it was possible to detect medium-range NOEs for the first time for this peptide. This allowed a much better-defined structure to be determined for Peptide T in comparison with earlier NMR and computational studies. Peptide structures consistent with the experimental restraints were generated using a restrained MD simulation with a full empirical force field. Residues 4,8 of Peptide T take on a well-defined structure with a heavy atom RMSD of 0.78 Å. The structure is stabilized by hydrogen bonding to side-chain oxygen atoms of Thr 4 and Thr 8, as well as backbone hydrogen bonding between residues 5 and 7 that forms this region into a classic ,-turn. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Temperature and urea induced denaturation of the TRP-cage mini protein TC5b: A simulation study consistent with experimental observationsPROTEIN SCIENCE, Issue 10 2009Z. Gattin Abstract The effects of temperature and urea denaturation (6M urea) on the dominant structures of the 20-residue Trp-cage mini-protein TC5b are investigated by molecular dynamics simulations of the protein at different temperatures in aqueous and in 6M urea solution using explicit solvent degrees of freedom and the GROMOS force-field parameter set 45A3. In aqueous solution at 278 K, TC5b is stable throughout the 20 ns of MD simulation and the trajectory structures largely agree with the NMR-NOE atom,atom distance data available. Raising the temperature to 360 K and to 400 K, the protein denatures within 22 ns and 3 ns, showing that the denaturation temperature is well below 360 K using the GROMOS force field. This is 40,90 K lower than the denaturation temperatures observed in simulations using other much used protein force fields. As the experimental denaturation temperature is about 315 K, the GROMOS force field appears not to overstabilize TC5b, as other force fields and the use of continuum solvation models seem to do. This feature may directly stem from the GROMOS force-field parameter calibration protocol, which primarily involves reproduction of condensed phase thermodynamic quantities such as energies, densities, and solvation free energies of small compounds representative for protein fragments. By adding 6M urea to the solution, the onset of denaturation is observed in the simulation, but is too slow to observe a particular side-chain side-chain contact (Trp6-Ile4) that was experimentally observed to be characteristic for the denatured state. Interestingly, using temperature denaturation, the process is accelerated and the experimental data are reproduced. [source] Tryptophanyl fluorescence lifetime distribution of hyperthermophilic ,-glycosidase from molecular dynamics simulation: A comparison with the experimental dataPROTEIN SCIENCE, Issue 9 2000Ettore Bismuto Abstract A molecular dynamics simulation approach has been utilized to understand the unusual fluorescence emission decay observed for ,-glycosidase from the hyperthermophilic bacterium Solfolobus sulfataricus (S,gly), a tetrameric enzyme containing 17 tryptophanyl residues for each subunit. The tryptophanyl emission decay of (S,gly) results from a bimodal distribution of fluorescence lifetimes with a short-lived component centered at 2.5 ns and a long-lived one at 7.4 ns Bismuto E, Nucci R, Rossi M, Irace G, 1999, Proteins 27:71,79). From the examination of the trajectories of the side chains capable of causing intramolecular quenching for each tryptophan microenvironment and using a modified Stern,Volmer model for the emission quenching processes, we calculated the fluorescence lifetime for each tryptophanyl residue of S,gly at two different temperatures, i.e., 300 and 365 K. The highest temperature was chosen because in this condition S,lgy evidences a maximum in its catalytic activity and is stable for a very long time. The calculated lifetime distributions overlap those experimentally determined. Moreover, the majority of trytptophanyl residues having longer lifetimes correspond to those originally identified by inspection of the crystallographic structure. The tryptophanyl lifetimes appear to be a complex function of several variables, such as microenvironment viscosity, solvent accessibility, the chemical structure of quencher side chains, and side-chain dynamics. The lifetime calculation by MD simulation can be used to validate a predicted structure by comparing the theoretical data with the experimental fluorescence decay results. [source] Solution structure of a novel T-cell adhesion inhibitor derived from the fragment of ICAM-1 receptor: Cyclo(1,8)-Cys-Pro-Arg-Gly-Gly-Ser-Val-CysBIOPOLYMERS, Issue 8 2009Bimo A. Tejo Abstract This study is aimed at elucidating the structure of a novel T-cell adhesion inhibitor, cyclo(1,8)-CPRGGSVC using one- and two-dimensional (2D) 1H NMR and molecular dynamics (MD) simulation. The peptide is derived from the sequence of its parent peptide cIBR (cyclo(1,12)-PenPRGGSVLVTGC), which is a fragment of intercellular adhesion molecule-1 (ICAM-1). Our previous results show that the cyclo(1,8)-CPRGGSVC peptide binds to the LFA-1 I-domain and inhibits heterotypic T-cell adhesion, presumably by blocking the LFA-1/ICAM-1 interactions. The structure of the peptide was determined using NMR and MD simulation in aqueous solution. Our results indicate that the peptide adopts type-I ,-turn conformation at the Pro2-Arg3-Gly4-Gly5 (PRGG) sequence. The ,-turn structure at the PRGG motif is well conserved in cIBR peptide and ICAM-1 receptor, which suggests the importance of the PRGG motif for the biological activity of cyclo(1,8)-CPRGGSVC peptide. Meanwhile, the Gly5-Ser6-Val7-Cys8-Cys1 (GSVCC) sequence forms a "turn-like" random coil structure that does not belong to any structured motif. Therefore, cyclo(1,8)-CPRGGSVC peptide has only one structured region at the PRGG sequence, which may play an important role in the binding of the peptide to the LFA-1 I-domain. The conserved ,-turn conformation of the PRGG motif in ICAM-1, cIBR, and cyclo(1,8)-CPRGGSVC peptides can potentially be used to design peptidomimetics. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 633,641, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Understanding the Plasticity of the ,/, Hydrolase Fold: Lid Swapping on the Candida antarctica Lipase B Results in Chimeras with Interesting Biocatalytic PropertiesCHEMBIOCHEM, Issue 3 2009Michael Skjøt Dr. Abstract The best of both worlds. Long molecular dynamics (MD) simulations of Candida antarctica lipase B (CALB) confirmed the function of helix ,5 as a lid structure. Replacement of the helix with corresponding lid regions from CALB homologues from Neurospora crassa and Gibberella zeae resulted in new CALB chimeras with novel biocatalytic properties. The figure shows a snapshot from the MD simulation. The Candida antarctica lipase B (CALB) has found very extensive use in biocatalysis reactions. Long molecular dynamics simulations of CALB in explicit aqueous solvent confirmed the high mobility of the regions lining the channel that leads into the active site, in particular, of helices ,5 and ,10. The simulation also confirmed the function of helix ,5 as a lid of the lipase. Replacing it with corresponding lid regions from the CALB homologues from Neurospora crassa and Gibberella zeae resulted in two new CALB mutants. Characterization of these revealed several interesting properties, including increased hydrolytic activity on simple esters, specifically substrates with C, branching on the carboxylic side, and much increased enantioselectivity in hydrolysis of racemic ethyl 2-phenylpropanoate (E>50), which is a common structure of the profen drug family. [source] Dependency of Tritium Retention in Graphite on Temperature Control of Molecular DynamicsCONTRIBUTIONS TO PLASMA PHYSICS, Issue 3-5 2010A. Ito Abstract We have investigated the carbon plasma facing material and hydrogen atom interaction by the use of molecular dynamics simulation to clarify chemical erosion processes on divertor plate. The present paper is our first try at elucidation of temperature dependence by the molecular dynamics. Temperature was controlled by using Langevin thermostat method. As a result, the retention of hydrogen atom achieve steady state, and the CH4 was generated, which was not found MD simulations without a temperature control method. About 30 percent of injected hydrogen atoms are retained. CH4 yields has a peak at 600 K, which accords with experimental results. A dominant path of CH4 generation found by the present molecular dynamics simulation is as follows: a CH is detached from eroded surface and then it grows into CH4 adsorbing hydrogen atoms via CH2 and CH3. In addition, we propose the problem that the hydrogen atom retention and CH,, yields depend on the thermal relaxation time in MD simulation using temperature control methods (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Comparison of Cyclodextrin-Dipeptide Inclusion Complexes in the Absence and Presence of Urea by Means of Capillary Electrophoresis, Nuclear Magnetic Resonance and Molecular ModelingEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2007Benjamin Waibel Abstract The use of capillary electrophoresis (CE) modified with cyclodextrin (CD) for the separation of stereoisomers of peptides is well established. To increase the solubility of ,-CD, urea is often added to the buffer which may influence the complexation of a CD with a guest molecule. The aim of the present study was to investigate the influence of urea on the complexation between dipeptides and ,-CD using Ala-Phe and Ala-Tyr as model compounds. For this purpose three different analytical methods were employed: capillary electrophoresis (CE), 1H-NMR spectroscopy and molecular dynamics simulations (MD). Electropherograms of the peptide enantiomers were different in the presence and absence of urea. For example, at pH,2.5 in the absence of urea the enantiomers of Ala-Tyr are not separated in contrast to the use of buffers containing urea. Applying "complexation-induced chemical shift (CICS)" in NMR spectroscopy and rotating frame Overhauser enhancement spectroscopy (ROESY) revealed differences in the complexation of the peptide enantiomers by ,-CD in the absence and presence of urea suggesting the stabilization of the complex through the phenolic hydroxyl group of tyrosine. MD simulations for different complexes were carried out with consideration of both water and urea molecules in solution. Simulations were performed for 1 ns. In conclusion, NMR spectroscopy and MD methods help to understand the structure of peptide-CD complexes and the separation and migration behavior in CE. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Formation of 2,4,D complexes on montmorillonites , an ab initio molecular dynamics studyEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 3 2007D. Tunega Summary Sorption of the anionic form of the pesticide 2,4,D (2,4,dichlorophenoxyacetic acid) on the surface of the clay mineral montmorillonite was investigated using a short-time ab initio molecular dynamics (MD) simulation at room temperature. Three different situations were modelled: sorption on a dry surface, on a hydrated surface and an intercalation between montmorillonite layers. In all three cases, the calcium cation compensates the excess negative charge of the montmorillonite layer and the negative charge of the 2,4,D anion. It was found that in all models with direct contact of the Ca2+ cation with the montmorillonite layer, the most stable position of Ca2+ is above the ditrigonal hole of the mineral layer. While in the case of a dry surface very stable bidentate binding is created between the 2,4,D anion and the Ca2+ cation, the formation of the monodentate complexes is preferred in all models that include water molecules. Hydrogen bonds formed between water molecules and the 2,4,D anion make a considerable contribution to the formation of the monodentate complexes. Tetrahedral substitutions in the montmorillonite layer have a significant effect on the formation of the complexes of any type. However, the MD simulations did not support the role of Ca2+ as a cation bridge in the adsorption mechanism. Calculations showed that hydrated 2,4,D···Ca2+ complexes are thermodynamically more stable than complexes in which the Ca2+ cation acts as a bridge to the surface. On the other hand, it is possible that phyllosilicates with a greater concentration of isomorphic substitutions (e.g. mica) will be able to form stable surface complexes with a cation bridge mechanism. [source] The effect of water content on proton transport in polymer electrolyte membranesFUEL CELLS, Issue 3-4 2002P. Commer Abstract We investigate proton transport in a polymer electrolyte membrane using continuum theory and molecular dynamics (MD) computer simulations. Specifically our goal is to understand the possible molecular origin of the effect of water content on the activation energy (AE) and pre-exponential factor of proton conductivity, in comparison with experimental observations reported for Nafion, where a decrease of AE with increasing water content has been observed. We study proton diffusion in a single pore, using a slab-like model. We find that although the average proton diffusion coefficient is several times smaller in a narrow pore than in a wide water-rich pore, its AE is almost unaffected by the pore width. This contradicts an earlier proposed conjecture that the sizable Coulomb potential energy barriers near the lattice of immobile point-like SO3, groups increase the AE in a narrow pore. Here we show that these barriers become smeared out by thermal motion of SO3, groups and by the spatial charge distribution over their atoms. This effect strongly diminishes the variation of the AE with pore width, which is also found in MD simulations. The pre-exponential factor for the diffusion process, however, decreases, indicating a limited number of pathways for proton transfer and the freezing out of degrees of freedom that contribute to the effective frequency of transfer. Decreasing the pore size diminishes bulk-like water regions in the pore, with only less mobile surface water molecules remaining. This hampers proton transfer. The increase of AE takes place only if the thermal motion of the SO3, head groups freezes out simultaneously with decreasing water content, but the effect is not profound. The stronger effect observed experimentally may thus be associated with some other rate-determining consecutive process, concerned with polymer dynamics, such as opening and closing of connections (bridges) between aqueous domains in the membrane under low water content. [source] Molecular dynamics simulations of polarizable DNA in crystal environmentINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 15 2006Volodymyr Babin Abstract We have investigated the role of the electrostatic description and cell environment in molecular dynamics (MD) simulations of DNA. Multiple unrestrained MD simulations of the DNA duplex d(CCAACGTTGG)2 have been carried out using two different force fields: a traditional description based on atomic point charges and a polarizable force field. For the time scales probed, and given the "right" distribution of divalent ions, the latter performs better than the nonpolarizable force field. In particular, by imposing the experimental unit cell environment, an initial configuration with ideal B-DNA duplexes in the unit cell acquires sequence-dependent features that very closely resemble the crystallographic ones. Simultaneously, the all-atom root-mean-square coordinates deviation (RMSD) with respect to the crystallographic structure is seen to decay. At later times, the polarizable force field is able to maintain this lower RMSD, while the nonpolarizable force field starts to drift away. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006 [source] Modeling zinc sulfhydryl bonds in zinc fingersINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 3-4 2001Johan Bredenberg Abstract Molecular dynamics simulations have been carried out employing three different model descriptions of the zinc sulfhydryl interactions in class II fingers. One bonded and two nonbonded models were studied. Two variant structures of the glucocorticoid receptor DNA-binding domain and a NMR structure from a fragment of methionyl-tRNA synthetase were subjected to long-time MD simulations with these models. Our analysis is focused on comparison with experimental and quantum mechanical data, concerning the local Zn-finger and overall structural and dynamic properties for these models. All models performed well, but the nonbonded models appeared to reproduce the protein dynamics in better agreement with experimental data than does the bonded description. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 230,244, 2001 [source] Protein folding simulations: From coarse-grained model to all-atom modelIUBMB LIFE, Issue 6 2009Jian Zhang Abstract Protein folding is an important and challenging problem in molecular biology. During the last two decades, molecular dynamics (MD) simulation has proved to be a paramount tool and was widely used to study protein structures, folding kinetics and thermodynamics, and structure,stability,function relationship. It was also used to help engineering and designing new proteins, and to answer even more general questions such as the minimal number of amino acid or the evolution principle of protein families. Nowadays, the MD simulation is still undergoing rapid developments. The first trend is to toward developing new coarse-grained models and studying larger and more complex molecular systems such as protein,protein complex and their assembling process, amyloid related aggregations, and structure and motion of chaperons, motors, channels and virus capsides; the second trend is toward building high resolution models and explore more detailed and accurate pictures of protein folding and the associated processes, such as the coordination bond or disulfide bond involved folding, the polarization, charge transfer and protonate/deprotonate process involved in metal coupled folding, and the ion permeation and its coupling with the kinetics of channels. On these new territories, MD simulations have given many promising results and will continue to offer exciting views. Here, we review several new subjects investigated by using MD simulations as well as the corresponding developments of appropriate protein models. These include but are not limited to the attempt to go beyond the topology based G,-like model and characterize the energetic factors in protein structures and dynamics, the study of the thermodynamics and kinetics of disulfide bond involved protein folding, the modeling of the interactions between chaperonin and the encapsulated protein and the protein folding under this circumstance, the effort to clarify the important yet still elusive folding mechanism of protein BBL, the development of discrete MD and its application in studying the ,,, conformational conversion and oligomer assembling process, and the modeling of metal ion involved protein folding. © 2009 IUBMB IUBMB Life, 61(6): 627,643, 2009 [source] MDLab: A molecular dynamics simulation prototyping environmentJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2010Trevor Cickovski Abstract Molecular dynamics (MD) simulation involves solving Newton's equations of motion for a system of atoms, by calculating forces and updating atomic positions and velocities over a timestep ,t. Despite the large amount of computing power currently available, the timescale of MD simulations is limited by both the small timestep required for propagation, and the expensive algorithm for computing pairwise forces. These issues are currently addressed through the development of efficient simulation methods, some of which make acceptable approximations and as a result can afford larger timesteps. We present MDLab, a development environment for MD simulations built with Python which facilitates prototyping, testing, and debugging of these methods. MDLab provides constructs which allow the development of propagators, force calculators, and high level sampling protocols that run several instances of molecular dynamics. For computationally demanding sampling protocols which require testing on large biomolecules, MDL includes an interface to the OpenMM libraries of Friedrichs et al. which execute on graphical processing units (GPUs) and achieve considerable speedup over execution on the CPU. As an example of an interesting high level method developed in MDLab, we present a parallel implementation of the On-The-Fly string method of Maragliano and Vanden-Eijnden. MDLab is available at http://mdlab.sourceforge.net. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010 [source] Using the local elevation method to construct optimized umbrella sampling potentials: Calculation of the relative free energies and interconversion barriers of glucopyranose ring conformers in waterJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2010Halvor S. Hansen Abstract A method is proposed to combine the local elevation (LE) conformational searching and the umbrella sampling (US) conformational sampling approaches into a single local elevation umbrella sampling (LEUS) scheme for (explicit-solvent) molecular dynamics (MD) simulations. In this approach, an initial (relatively short) LE build-up (searching) phase is used to construct an optimized biasing potential within a subspace of conformationally relevant degrees of freedom, that is then used in a (comparatively longer) US sampling phase. This scheme dramatically enhances (in comparison with plain MD) the sampling power of MD simulations, taking advantage of the fact that the preoptimized biasing potential represents a reasonable approximation to the negative of the free energy surface in the considered conformational subspace. The method is applied to the calculation of the relative free energies of ,- D -glucopyranose ring conformers in water (within the GROMOS 45A4 force field). Different schemes to assign sampled conformational regions to distinct states are also compared. This approach, which bears some analogies with adaptive umbrella sampling and metadynamics (but within a very distinct implementation), is shown to be: (i) efficient (nearly all the computational effort is invested in the actual sampling phase rather than in searching and equilibration); (ii) robust (the method is only weakly sensitive to the details of the build-up protocol, even for relatively short build-up times); (iii) versatile (a LEUS biasing potential database could easily be preoptimized for small molecules and assembled on a fragment basis for larger ones). © 2009 Wiley Periodicals, Inc. J Comput Chem 2010 [source] Molecular dynamics simulations of fluid methane properties using ab initio intermolecular interaction potentialsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2009Shih-Wei Chao Abstract Intermolecular interaction energy data for the methane dimer have been calculated at a spectroscopic accuracy and employed to construct an ab initio potential energy surface (PES) for molecular dynamics (MD) simulations of fluid methane properties. The full potential curves of the methane dimer at 12 symmetric conformations were calculated by the supermolecule counterpoise-corrected second-order Møller-Plesset (MP2) perturbation theory. Single-point coupled cluster with single and double and perturbative triple excitations [CCSD(T)] calculations were also carried out to calibrate the MP2 potentials. We employed Pople's medium size basis sets [up to 6-311++G(3df, 3pd)] and Dunning's correlation consistent basis sets (cc-pVXZ and aug-cc-pVXZ, X = D, T, Q). For each conformer, the intermolecular carbon,carbon separation was sampled in a step 0.1 Å for a range of 3,9 Å, resulting in a total of 732 configuration points calculated. The MP2 binding curves display significant anisotropy with respect to the relative orientations of the dimer. The potential curves at the complete basis set (CBS) limit were estimated using well-established analytical extrapolation schemes. A 4-site potential model with sites located at the hydrogen atoms was used to fit the ab initio potential data. This model stems from a hydrogen,hydrogen repulsion mechanism to explain the stability of the dimer structure. MD simulations using the ab initio PES show quantitative agreements on both the atom-wise radial distribution functions and the self-diffusion coefficients over a wide range of experimental conditions. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009 [source] Strategies to model the near-solute solvent molecular density/polarizationJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 5 2009Pei-Kun Yang Abstract The solvent molecular distribution significantly affects the behavior of the solute molecules and is thus important in studying many biological phenomena. It can be described by the solvent molecular density distribution, g, and the solvent electric dipole distribution, p. The g and p can be computed directly by counting the number of solvent molecules/dipoles in a microscopic volume centered at r during a simulation or indirectly from the mean force F and electrostatic field E acting on the solvent molecule at r, respectively. However, it is not clear how the g and p derived from simulations depend on the solvent molecular center or the solute charge and if the gF and pE computed from the mean force and electric field acting on the solvent molecule, respectively, could reproduce the corresponding g and p obtained by direct counting. Hence, we have computed g,p,gF, and pE using different water centers from simulations of a solute atom of varying charge solvated in TIP3P water. The results show that gF and pE can reproduce the g and p obtained using a given count center. This implies that rather than solving the coordinates of each water molecule by MD simulations, the distribution of water molecules could be indirectly obtained from analytical formulas for the mean force F and electrostatic field E acting on the solvent molecule at r. Furthermore, the dependence of the g and p distributions on the solute charge revealed provides an estimate of the change in g and p surrounding a biomolecule upon a change in its conformation. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source] The implementation of a fast and accurate QM/MM potential method in AmberJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2008Ross C. Walker Abstract Version 9 of the Amber simulation programs includes a new semi-empirical hybrid QM/MM functionality. This includes support for implicit solvent (generalized Born) and for periodic explicit solvent simulations using a newly developed QM/MM implementation of the particle mesh Ewald (PME) method. The code provides sufficiently accurate gradients to run constant energy QM/MM MD simulations for many nanoseconds. The link atom approach used for treating the QM/MM boundary shows improved performance, and the user interface has been rewritten to bring the format into line with classical MD simulations. Support is provided for the PM3, PDDG/PM3, PM3CARB1, AM1, MNDO, and PDDG/MNDO semi-empirical Hamiltonians as well as the self-consistent charge density functional tight binding (SCC-DFTB) method. Performance has been improved to the point where using QM/MM, for a QM system of 71 atoms within an explicitly solvated protein using periodic boundaries and PME requires less than twice the cpu time of the corresponding classical simulation. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Application of torsion angle molecular dynamics for efficient sampling of protein conformationsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2005Jianhan Chen Abstract We investigate the application of torsion angle molecular dynamics (TAMD) to augment conformational sampling of peptides and proteins. Interesting conformational changes in proteins mainly involve torsional degrees of freedom. Carrying out molecular dynamics in torsion space does not only explicitly sample the most relevant degrees of freedom, but also allows larger integration time steps with elimination of the bond and angle degrees of freedom. However, the covalent geometry needs to be fixed during internal coordinate dynamics, which can introduce severe distortions to the underlying potential surface in the extensively parameterized modern Cartesian-based protein force fields. A "projection" approach (Katritch et al. J Comput Chem 2003, 24, 254,265) is extended to construct an accurate internal coordinate force field (ICFF) from a source Cartesian force field. Torsion crossterm corrections constructed from local molecular fragments, together with softened van der Waals and electrostatic interactions, are used to recover the potential surface and incorporate implicit bond and angle flexibility. MD simulations of dipeptide models demonstrate that full flexibility in both the backbone ,/, and side chain ,1 angles are virtually restored. The efficacy of TAMD in enhancing conformational sampling is then further examined by folding simulations of small peptides and refinement experiments of protein NMR structures. The results show that an increase of several fold in conformational sampling efficiency can be reliably achieved. The current study also reveals some complicated intrinsic properties of internal coordinate dynamics, beyond energy conservation, that can limit the maximum size of the integration time step and thus the achievable gain in sampling efficiency. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1565,1578, 2005 [source] A force-field description of short-range repulsions for high density alkane molecular dynamics simulationsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2004Joseph M. Hayes Abstract The use of Buckingham (exp-6) van der Waals potentials in molecular dynamics (MD) simulations can quite successfully reproduce experimental thermodynamic data at low densities. However, they are less successful in producing a description of the repulsive regions of the potential energy surface (PES) that is in accord with the results of high-level ab initio computations. We show that Morse potentials can be parameterized to give excellent fits to both the attractive and repulsive regions of the PES. The best set of alkane van der Waals Morse function parameters reported to date for the description of nonbond repulsive interactions is presented, as determined by comparison with both ab initio and experimental results. C,C, H,H and C,H atom-pair potentials employing parameter sets based on the use of the geometric mean in the fitting procedure are found to be portable from methane to n- butane. Fitting to a combination of methane dimer interaction energies and forces from ab initio calculations yields parameter sets whose performance is superior to those determined from the interaction energies alone. Used in MD simulations, our newly developed parameter sets predict thermodynamic functions that show better agreement with experiment than those based on parameter sets in common use. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1953,1966, 2004 [source] Rigid-body dynamics in the isothermal-isobaric ensemble: A test on the accuracy and computational efficiencyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 8 2003Wataru Shinoda Abstract We have developed a time-reversible rigid-body (rRB) molecular dynamics algorithm in the isothermal-isobaric (NPT) ensemble. The algorithm is an extension of rigid-body dynamics [Matubayasi and Nakahara, J Chem Phys 1999, 110, 3291] to the NPT ensemble on the basis of non-Hamiltonian statistical mechanics [Martyna, G. J. et al., J Chem Phys 1994, 101, 4177]. A series of MD simulations of water as well as fully hydrated lipid bilayer systems have been undertaken to investigate the accuracy and efficiency of the algorithm. The rRB algorithm was shown to be superior to the state-of-the-art constraint-dynamics algorithm SHAKE/RATTLE/ROLL, with respect to computational efficiency. However, it was revealed that both algorithms produced accurate trajectories of molecules in the NPT as well as NVT ensembles, as long as a reasonably short time step was used. A couple of multiple time-step (MTS) integration schemes were also examined. The advantage of the rRB algorithm for computational efficiency increased when the MD simulation was carried out using MTS on parallel processing computer systems; total computer time for MTS-MD of a lipid bilayer using 64 processors was reduced by about 40% using rRB instead of SHAKE/RATTLE/ROLL. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 920,930, 2003 [source] Comparison of linear-scaling semiempirical methods and combined quantum mechanical/molecular mechanical methods for enzymic reactions.JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 14 2002Abstract QM/MM methods have been developed as a computationally feasible solution to QM simulation of chemical processes, such as enzyme-catalyzed reactions, within a more approximate MM representation of the condensed-phase environment. However, there has been no independent method for checking the quality of this representation, especially for highly nonisotropic protein environments such as those surrounding enzyme active sites. Hence, the validity of QM/MM methods is largely untested. Here we use the possibility of performing all-QM calculations at the semiempirical PM3 level with a linear-scaling method (MOZYME) to assess the performance of a QM/MM method (PM3/AMBER94 force field). Using two model pathways for the hydride-ion transfer reaction of the enzyme dihydrofolate reductase studied previously (Titmuss et al., Chem Phys Lett 2000, 320, 169,176), we have analyzed the reaction energy contributions (QM, QM/MM, and MM) from the QM/MM results and compared them with analogous-region components calculated via an energy partitioning scheme implemented into MOZYME. This analysis further divided the MOZYME components into Coulomb, resonance and exchange energy terms. For the model in which the MM coordinates are kept fixed during the reaction, we find that the MOZYME and QM/MM total energy profiles agree very well, but that there are significant differences in the energy components. Most significantly there is a large change (,16 kcal/mol) in the MOZYME MM component due to polarization of the MM region surrounding the active site, and which arises mostly from MM atoms close to (<10 Å) the active-site QM region, which is not modelled explicitly by our QM/MM method. However, for the model where the MM coordinates are allowed to vary during the reaction, we find large differences in the MOZYME and QM/MM total energy profiles, with a discrepancy of 52 kcal/mol between the relative reaction (product,reactant) energies. This is largely due to a difference in the MM energies of 58 kcal/mol, of which we can attribute ,40 kcal/mol to geometry effects in the MM region and the remainder, as before, to MM region polarization. Contrary to the fixed-geometry model, there is no correlation of the MM energy changes with distance from the QM region, nor are they contributed by only a few residues. Overall, the results suggest that merely extending the size of the QM region in the QM/MM calculation is not a universal solution to the MOZYME- and QM/MM-method differences. They also suggest that attaching physical significance to MOZYME Coulomb, resonance and exchange components is problematic. Although we conclude that it would be possible to reparameterize the QM/MM force field to reproduce MOZYME energies, a better way to account for both the effects of the protein environment and known deficiencies in semiempirical methods would be to parameterize the force field based on data from DFT or ab initio QM linear-scaling calculations. Such a force field could be used efficiently in MD simulations to calculate free energies. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1314,1322, 2002 [source] | |||||||||||||||||||||||||