Hydration of T-antigen Gal beta(1-3)GalNAc and the isomer Gal beta(1-3)GlcNAc by molecular dynamics simulations

We present a 250 ps molecular dynamics simulation of the T-antigen Gal beta(1-3)GalNAc and its isomer Gal beta(1-3)GlcNAc in the classic Gibbs Ensemble, Number of particles, Pressure and Temperature (NPT) with explicit representation of 432 water molecules. We computed the radial distribution function, equilibrium conformation, intramolecular and intermolecular hydrogen bonds, and water residence time to characterize the hydration pattern of these sugars, which are not very different and exhibit hydrophilic behavior. Based on hydration dynamics, it was concluded that these sugars should be classified as negative hydrated. Formation of an intramolecular hydrogen bond between the ring oxygen atom O5 of the first unit and the OH4' group of glycoside of the second unit might influence interaction with the antigenic receptor and could explain the main difference of affinities between them.     

Molecular dynamics simulations of shear-driven gas flows in nano-channels

Using the recently developed smart wall molecular dynamics algorithm, shear-driven gas flows in nano-scale channels are investigated to reveal the surface–gas interaction effects for flows in the transition and free molecular flow regimes. For the specified surface properties and gas–surface pair interactions, density and stress profiles exhibit a universal behavior inside the wall force penetration region at different flow conditions. Shear stress results are utilized to calculate the tangential momentum accommodation coefficient (TMAC) between argon gas and FCC walls. The TMAC value is shown to be independent of the flow properties and Knudsen number in all simulations. Velocity profiles show distinct deviations from the kinetic theory based solutions inside the wall force penetration depth, while they match the linearized Boltzmann equation solution outside these zones. Results indicate emergence of the wall force field penetration depth as an additional length scale for gas flows in nano-channels, breaking the dynamic similarity between rarefied and nano-scale gas flows solely based on the Knudsen and Mach numbers.     

Molecular dynamics simulations of oscillatory flows in microfluidic channels

In this paper we apply the direct non-equilibrium molecular dynamics technique to oscillatory flows of fluids in microscopic channels. Initially, we show that the microscopic simulations resemble the macroscopic predictions based on the Navier–Stokes equation very well for large channel width, high density and low temperature. Further simulations for high temperature and low density show that the non-slip boundary condition traditionally used in the macroscopic equation is greatly compromised when the fluid–wall interactions are the same as the fluid–fluid interactions. Simulations of a system with very narrow channel width confirm earlier findings of Poiseuille flow, namely, that the velocity profiles are modulated. We find that these modulations cannot be explained by the local area density model.

Molecular dynamics simulations of thermal effects in nanometric cutting process

Understanding the basic action of how material removing in nanoscale is a critical issue of producing well-formed components.In order to clarify thermal effects on material removal at atomic level,molecular dynamics(MD)simulations of nanometric cutting of mono-crystalline copper are performed with Morse,EAM and Tersoff potential.The effects of cutting speed on temperature distribution are investigated.The simulation results demonstrate that the temperature distribution shows a roughly concentric shape aroun...     

Molecular dynamics simulations of Oxprenolol and Propranolol in a DPPC lipid bilayer

Extensive microscopic molecular dynamics simulations have been performed to study the effects of tow β-blocker drugs (Propranolol, Oxprenolol) on fully hydrated dipalmitoylphosphatidylcholine (DPPC) in the fluid phase at 323 K. Simulation of 4 systems containing varying concentrations of drugs was carried out. For the purpose of comparison, a fully hydrated DPPC bilayer without drugs was also studied at the same level of simulation technique which has been done on 4 other systems. The length of each simulation was 100 ns. The effects of concentrations of both drugs were analyzed on lipid bilayer properties, such as electrostatic potential, order parameter, diffusion coefficients, and hydrogen bond formation, etc. Penetration of water in the bilayer system was also investigated using radial distribution function analysis. Efficacy of varying concentrations of both drugs has no significant effect on P–N vector. Consistent with experimental results, by increasing the concentration of Propranolol, the thickness of the bilayer was increased.     

Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature.

This paper describes molecular dynamics simulations of prion protein at 300 and 500 K. This was undertaken to gain insight into the factors involved in the stability of prion protein. Simulations were done using the Particle Mesh Ewald (PME) method using a homology model of the C-terminal fragment of human prion protein and the NMR structure of the human prion protein. The simulations at both 300 and 500 K were stable. Simulations were also undertaken with a mutant known to be associated with prion disease: Asp178Asn. The Asp178Asn simulation trajectory was observed to be much less stable than for the wild-type protein trajectory. Significant breakdown in secondary structure was observed for Asp178Asn at 500 K.     

Molecular dynamics simulations of the relaxation processes in the condensed matter on GPUs

We report on simulation technique and benchmarks for molecular dynamics simulations of the relaxation processes in solids and liquids using the graphics processing units (GPUs). The implementation of a many-body potential such as the embedded atom method (EAM) on GPU is discussed. The benchmarks obtained by LAMMPS and HOOMD packages for simple Lennard-Jones liquids and metals using EAM potentials are presented for both Intel CPUs and Nvidia GPUs. As an example the crystallization rate of the supercooled Al melt is computed.     

Molecular dynamics simulations to aid the rational design of organic friction modifiers

Molecular dynamics simulations were performed under conditions of constant volume and temperature and of constant pressure and temperature to elucidate the structure activity relationships of a series of non-ionic surfactant molecules derived from vegetable fat and employed as friction modifiers in commercial engine oils. The simulations show the extent to which intermolecular hydrogen bonding is important in determining the stability of the monolayer formed by the surfactant molecules and show that mono-alkanoyl glyceride molecules are able to pack more efficiently, forming significantly more intermolecular hydrogen bonds and occupying approximately half the volume needed by di-alkanoyl glyceride molecules. Density profiles are presented which show significant mixing of the hydrophobic tail groups and a non-polar solvent. The distribution of torsion angles in the tail groups shows that the conformation is consistent with a liquid at finite temperature rather than a crystal structure. The measured friction coefficients of equimolar solutions of the glycerides show that the efficacy as friction modifiers varies in the order mono-, di- and the tri-oleyl glyceride, which is consistent with the efficacy of film formation predicted by the molecular dynamics calculations.     

氯霉素分子印迹聚合物预组装过程的分子动力学研究

以氯霉素(CAP)为模板分子,甲基丙烯酸(MAA)、丙烯酸(AA)、丙烯酰胺(AM)、甲基丙烯酸甲酯(MMA)为功能单体,采用分子动力学方法研究了不同预组装体系中CAP与功能单体的相互作用,考察了溶剂(氯仿、甲醇、乙腈)对预组装体系的影响,并采用试验方法验证模拟结果,最后研究了预组装体系中CAP与功能单体相互作用距离。结果表明:模拟结果与实验结果一致,在甲醇溶剂中,CAP与功能单体相互作用强弱顺序为MAA>AA>AM>MMA;乙腈溶剂中顺序为AM>MAA>AA>MMA。CAP与功能单体相互作用基团的距离在1.8~5.0,两者间可能存在较强的非共价结合作用。     

Molecular basis of agonicity and antagonicity in the androgen receptor studied by molecular dynamics simulations

Treatment of prostate cancer patients with antiandrogens is initially successful, though the therapy often becomes refractory over the time. This mechanism is not fully understood, but the presence of androgen receptor (AR) mutant forms which are activated by antiandrogens and other endogenous ligands, and overexpression of the receptor have been suggested. In an attempt to explain the molecular basis for agonicity and antagonicity in the androgen receptor, and the changes on biological activity of subtle modifications at the ligand and receptor (mutations) level, molecular dynamics simulations were performed on the androgen receptor wild type (WT), and T877A and W741 mutant forms, complexed with several non-steroidal androgens. The stabilizing role of residues from helices 3, 5, 11 and 12 was observed in non-steroidal androgens R-3, S-1, and R-bicalutamide and hydroxyflutamide in resistant mutations. In the AR WT antiandrogen R-bicalutamide complex, destabilization of M895 by both W741 and the sulfonyl linkage of the ligand may be responsible for reported antagonism. Changes in the ligand or mutations alleviating this effect were observed to stabilize the receptor in the active conformation, thus developing resistance to R-bicalutamide. The results presented provide a plausible explanation for the molecular basis of agonicity and antagonicity in the androgen receptor, and complement previous studies using static crystal structures, incorporating for the first time protein dynamics into the analysis. Thus, our results provide a valuable framework for the structure-based design of improved antiandrogens.     

Molecular dynamics simulations of isoleucine-release pathway in GAF domain of N-CodY from Bacillus Subtilis

The GAF domain located in the N-terminal motifs of CodY (N-CodY) is responsible for increasing the affinity of CodY to its target sites on DNA by its interaction with the branched chain amino acids (BCAAs) involving isoleucine, leucine and valine. The study of the interaction of GAF domain with isoleucine gains much attention in recent years, but the mechanism of isoleucine release still remains unclear. In this paper, a conventional molecular dynamics (MD) and force probe molecular dynamics (FPMD) simulations have been performed with the aim to understand how the isoleucine ligand escapes from the GAF domain of N-CodY from Bacillus subtilis. The MD results reveal that the ligand release is a gradual process, which is accompanied by the movement of the loop between β3 and β4. During the periods of ligand escaping from the bottom to the top of binding pocket, isoleucine forms hydrogen bonds one after another with series of residues, such as ARG61, THR96, PHE98, VAL100, GLU101 and ASN102, under the mediation of hydrophobic contacts. The FPMD results show that the easiest way to pull ligand out of the cavity is along x direction (i.e. the direction is opposite to MET62).     

基于温度对H型水合物稳定性影响的分子动力学模拟

采用分子动力学模拟平台(ME),计算了H型水合物的性质及结构参数,并通过分析水合物晶体的最终构像、径向分布函数、均方位移、扩散系数、模拟体系势能等微观特征参数,考察了温度对H型水合物晶体结构稳定性的影响。模拟结果表明,随温度的升高,H型水合物的稳定性降低,笼型结构有分解之趋势。     

New solitonic solutions to a (3+1)-dimensional Jimbo-Miwa equation

Performing computerized symbolic computation, we are able to present new analytic solutions of a (3+1)-dimensional Jimbo-Miwa equation which does not pass any of the conventional integrability tests. Applying the generalized tanh method, we have found such exact solutions as both the nontraveling-solitonic and traveling-solitary waves.     

Structural dynamics of Casein Kinase I (CKI) from malarial parasite Plasmodium falciparum (Isolate 3D7): Insights from theoretical modelling and molecular simulations

The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation. Bi-lobed catalytic domain of PfCKI shares a high degree of secondary structure topology with CKI domains of rice, human, and mouse indicating co-evolution of these kinases. Molecular docking study revealed that ATP binds to the active site where the glycine-rich ATP-binding motif (G16-X-G18-X-X-G21) along with few conserved residues plays a crucial role maintaining stability of the complex. Structural superposition of PfCKI with close structural homologs depicted that the location and length of important loops are different, indicating the dynamic properties of these loops among CKIs, which is consistent with principal component analysis (PCA). PCA displayed that the overall global motion of ATP-bound form is comparatively higher than that of apo form. The present study provides insights into the structural features of PfCKI, which could contribute towards further understanding of related protein structures, dynamics of catalysis and phosphorylation mechanism in these important STKs from malarial parasite in near future.     

氯化钾溶液中离子水化的分子动力学模拟

使用Material Studio软件包中的COMPASS力场,采用分子动力学模拟的方法研究了温度为298.15 K时,浓度分别为1.065 mol/L、2.140 mol/L、3.129 mol/L的氯化钾溶液中离子水化的微观结构和动力学性质.发现浓度对离子近程水化的结构有一定的影响,随着溶液浓度的增加O-O径向分布...     

Dynamical analysis of the conformation of the active site of porcine pancreatic elastase in native and Michaelis complex states. Molecular dynamics simulations

Mechanistic details of events preceeding and occurring during enzymatic catalysis are extremely difficult to obtain experimentally. While molecular dynamics methods permit the simulation of discrete steps along the catalytic pathway, they also can overwhelm the investigator with a mountain of structural details, necessitating the development of specific analytic tools. Based on recent crystallographic data, several molecular dynamics simulations have been performed using the AMBER 3.0 program package. Two different simulations for the hydrated native enzyme (100 and 50 ps) and two simulations (30 and 70 ps) of the Michaelis complex of this enzyme with the substrate (Thr-Pro-nVal-Leu-Tyr-Thr) have been performed. Dynamical properties of the active site (especially the catalytic tetrad: Ser-195, His-57, Asp-102 and Ser-214; chymotrypsinogen numbering system) have been examined using the program MD_ANALYSIS_1. It, together with the program MDKINO, facilitates analysis of dynamical changes of conformation (especially the hydrogen bond network) of the active site. Hydrogen bonding among Asp-102, Ser-214 and His-57 was quite stable, but the catalytic Ser-195 sidechain was flexible. Therefore the catalytically crucial H-bond between HO_γ (Ser-195) and N_ϵ (His-57) is relatively labile. In the native case (i.e. without substrate) this H-bond was never formed due to competition for the acceptor atom (N_ϵ) between water molecules and the HO_γ group. In the Michaelis complex the H-bond is more readily formed, although the sidechain (Ser-195) may sometimes change its conformation do to the influence of the carbonyl group of Ser-214. Due to the dynamical motion of the enzyme there were six different short periods in which the distance between both heavy atoms in this crucial H-bond was less than 2.6 Å, which may facilitate proton transfer from Ser-195 to His-57 (the first step during the proper catalysis). These results suggest mechanistic details about the precise clockwork of a functioning enzyme.     

Enhanced sampling by multiple molecular dynamics trajectories: carbonmonoxy myoglobin 10 micros A0-->A(1-3) transition from ten 400 picosecond simulations

The utility of multiple trajectories to extend the time scale of molecular dynamics simulations is reported for the spectroscopic A-states of carbonmonoxy myoglobin (MbCO). Experimentally, the A0-->A(1-3) transition has been observed to be 10 micros at 300 K, which is beyond the time scale of standard molecular dynamics simulations. To simulate this transition, 10 short (400 ps) and two longer time (1.2 ns) molecular dynamics trajectories, starting from five different crystallographic and solution phase structures with random initial velocities centered in a 37 A radius sphere of water, have been used to sample the native-fold of MbCO. Analysis of the ensemble of structures gathered over the cumulative 5.6 ns reveals two biomolecular motions involving the side chains of His64 and Arg45 to explain the spectroscopic states of MbCO. The 10 micros A0-->A(1-3) transition involves the motion of His64, where distance between His64 and CO is found to vary up to 8.8 +/- 1.0 A during the transition of His64 from the ligand (A(1-3)) to bulk solvent (A0). The His64 motion occurs within a single trajectory only once, however the multiple trajectories populate the spectroscopic A-states fully. Consequently, multiple independent molecular dynamics simulations have been found to extend biomolecular motion from 5 ns of total simulation to experimental phenomena on the microsecond time scale.     

H-POSS表面润湿性的分子动力学模拟

采用分子动力学模拟方法研究了水滴在多面体低聚倍半硅氧烷(H-POSS)固体表面的润湿性能,H-POSS分子和水分子分别采用COMPASS力场和SPC力场模型。模拟得到H-POSS基体密度为1.84g/cm~3,且X射线衍射模拟发现基体具有明显衍射峰,表现出晶体特性,说明COMPASS力场适用于H-POSS基体的构建与研究。H-POSS表面水接触角的模拟值为104.9°,具有疏水性能。通过直接水解法由三氯硅烷(HSiCl_3)实验合成出H-POSS样品,傅立叶红外表征(FT-IR)发现,在2260、1142和871cm~(-1)波数位置出现吸收峰,证实了所合成的样品为H-POSS。其表面水接触角的实验值为109.3°,与模拟值的相对误差仅为4%,说明分子动力学方法可应用于计算H-POSS材料表面润湿性。模拟结果还表明体系温度影响H-POSS材料的表面润湿性,增大体系温度,表面疏水性能降低。     

分子动力学模拟聚赖氨酸在晶格界面上的吸附

分子模拟为从微观角度理解生物大分子提供了有利的工具。本文采用分子动力学方法研究在Pt(100)、Pt(110)及Pt (111)三种晶格界面上聚十赖氨酸分子的吸附,以从分子水平上研究蛋白质吸附的动态过程和机理。界面的作用使部分聚十赖氨酸分子出现了较明显的二面角变化,说明吸附过程中界面的特性对聚赖氨酸的分子结构有影响;在Pt(100)与Pt(111)界面上,聚十赖氨酸分子构象变化较大,Pt(110)变化较小。聚十赖氨酸分子在吸附中,能量变化与分子构象变化的结果一致,构象变化较大的Pt(100)和Pt(111)界面上聚十赖氨酸分子能量的平均值高于Pt(110)。聚十赖氨酸分子在Pt(100)与Pt(111)界面上先远离界面运动,然后在某位置稳定波动;在Pt(110)界面上先靠近界面运动一段时间后又远离界面。