From Molecular to Process Simulation: Novel Approaches to the Prediction of Phase Equilibria and PVT Behavior Based on Molecular/Quantum Mechanics and Molecular Dynamics Simulations

Abstract

Actually, in modern process simulators, more than 75% of the code implemented is dedicated to physical properties estimation, calculation and predictions. Data banks storing pure component parameters and binary interaction parameters for phase equilibrium calculations are extensively used and continuously implemented in actual process simulators. This gives an idea of the important role physical properties availability plays in process simulation.

In this paper we propose a new way for coupling molecular and process simulation. The basic machinery is to resort to molecular/quantum mechanics and molecular dynamics simulation techniques for generating the parameters of some equations of state that will subsequently be used for the prediction of phase equilibria and PVT behavior of small and polymeric molecules as well. This information, in turn, will be used as input in the process simulator, thus creating a final and well-defined bridge between molecular and process simulations in chemical engineering.     

Molecular simulation for predicting the rheological properties of polymer melts

ABSTRACT

Bottom-up prediction that links materials chemistry to their properties is a constant theme in polymer simulation. Rheological properties are particularly challenging to predict because of the extended time scales involved as well as large uncertainty in the stress output from molecular simulation. This review focuses on the application of molecular simulation in the prediction of such properties, including approaches solely based on molecular simulation and its integration with rheological models. Most attention is given to the prediction of quantitative properties, in particular, those most studied such as shear viscosity and linear viscoelasticity. Studies on the fundamental understanding of rheology are referenced only when they are directly relevant to the property prediction. The review starts with an overview of the major methods for extracting rheological properties from molecular simulation, using bead-spring chain models as a sandbox system. It then discusses materials-specific prediction using chemically-realistic models, including systematically coarse-grained models that allow the mapping between scales. Finally, integrating molecular simulation with rheological models extends the prediction to highly entangled polymers. Recent development of several multiscale predictive frameworks allowed the successful prediction of rheological properties from the chemical structure for polymers of experimentally relevant molecular weights.     

Molecular Dynamics Study of the Diffusion of Hydrogen in Solid Palladium

Abstract

The diffusion of hydrogen atoms in solid palladium is studied via a molecular dynamics simulation. In this calculation, the palladium atoms are fixed on the sites of the fcc lattice and the hydrogen atoms are initially put on the O (octahedral) sites. Through the present molecular dynamics simulation, the diffusion constant and activation energy are calculated for several different concentrations of hydrogen atoms. We find that the hydrogen atoms show jump motions between the O sites which lead to super diffusion in the solid palladium. We have also obtained the temperature dependence and concentration dependence of the vacancy factor and jump correlation functions.     

Molecular dynamics simulation of proteins under high pressure: Structure,function and thermodynamics

BackgroundMolecular dynamics (MD) simulation is well-recognized as a powerful tool to investigate protein structure, function, and thermodynamics. MD simulation is also used to investigate high pressure effects on proteins. For conducting better MD simulation under high pressure, the main issues to be addressed are: (i) protein force fields and water models were originally developed to reproduce experimental properties obtained at ambient pressure; and (ii) the timescale to observe the pressure effect is often much longer than that of conventional MD simulations.Scope of reviewFirst, we describe recent developments in MD simulation methodologies for studying the high-pressure structure and dynamics of protein molecules. These developments include force fields for proteins and water molecules, and enhanced simulation techniques. Then, we summarize recent studies of MD simulations of proteins in water under high pressure.Major conclusionsRecent MD simulations of proteins in solution under pressure have reproduced various phenomena identified by experiments using high pressure, such as hydration, water penetration, conformational change, helix stabilization, and molecular stiffening.General significanceMD simulations demonstrate differences in the properties of proteins and water molecules between ambient and high-pressure conditions. Comparing the results obtained by MD calculations with those obtained experimentally could reveal the mechanism by which biological molecular machines work well in collaboration with water molecules.     

Molecular Dynamics Simulation of CaF2 Structure in Crystalline,Superionic and Molten Phases

Abstract

We describe here a number of molecular dynamics simulations on calcium fluoride over a range of temperatures spanning the transitions to the superionic and molten state. The simulation temperatures are 1400, 1590, 1800, 2000, 2200 K. By using the bond spherical harmonics method with equal neighbor number, we have studied the structure and bond orientation of cation sublattice and anion sublattice in superionic conductor CaF₂. The bond order parameters Q₁ have been calculated both for the computer generated instataneous configurations from the simulation system and for the standard configurations from the normal distribution model of bond orientation. The comparison of Q₁ between the molecular dynamics simulation and the normal distribution model shows that not only the cation sublattice but also the anion sublattice can be described by the normal distribution model. The cations keep their original fcc frame, but in the anion case there is a great deal of random distortions from the original anion sublattice.     

Structural Transformations of Ice at High Pressures Via Molecular Dynamics Simulations

Abstract

A simple classical model is used for the study of the structural transformations of ice under high pressures, such as ice VIII to VII and X, via classical molecular dynamics (MD) simulation. In the present MD simulation, pair potentials of a simple form between pair of atoms and a thee-body potential representing the H-O-H angle dependence, originally developed by Kawamura et al., were used. Starting with a stable ice VIII at low pressure and low temperature, we have carried out two different MD runs, one with increasing pressure keeping the temperature constant (simulation I) and the other with increasing temperature under constant pressure (simulation II). From these MD simulations we have obtained the structural transformations from ice VIII to VII for both simulations; the former was finally transformed into ice X for the simulation I. The present results are compatible with recent experiments on high pressure ices.     

On the Accuracy Of Some Common Molecular Dynamics Algorithms

Abstract

Attention is drawn to the fact that some of the algorithms used in the simulation of molecular dynamics are less accurate than is commonly believed. In particular, we show that many of the “Verlet-equivalent” integration schemes are not equivalent to the Verlet algorithm, and consequently are not necessarily third order schemes which exhibit exact time-reversal symmetry. Of this class of algorithms, only Beeman's technique is found to generate the optimal positions and velocities for a third order technique. It is also pointed out that the method of constraints introduces errors of O(τ³) into the calculated position, and hence limits the accuracy of simulations that employ this method to second order.     

Gibbs-Ensemble Molecular Dynamics: Liquid-Gas Equilibria for Lennard-Jones Spheres and n-Hexane

Abstract

We present a novel method to simulate phase equilibria in atomic and molecular systems. The method is a Molecular Dynamics version of the Gibbs-Ensemble Monte Carlo technique, which has been developed some years ago for the direct simulation of phase equilibria in fluid systems. The idea is to have two separate simulation boxes, which can exchange particles (or molecules) in a thermodynamically consistent fashion. Here we pres the derivation of the generalized equations of motion and discuss the relation of the resulting trajectory averages to the relevant ensemble. We test this Gibbs-Ensemble Molecular Dynamics algorithm by applying it to an atomic and a molecular system, i.e. to the liquid-gas coexistence in a Lennard-Jones fluid and in n-hexane. In both cases our results are in good accord with previous mean field and Gibbs-Ensemble Monte Carlo results as well as with the experimental data in the case of hexane. We also show that our Gibbs-Ensemble Molecular Dynamics algorithm like other Molecular Dynamics techniques can be used to study the dynamics of the system. Self-diffusion coefficients calculated with this method are in agreement with the result of conventional constant temperature Molecular Dynamics.     

Structure of Supercritical Fluid Krypton at Small Scattering Angle Using Parallel Molecular Dynamics Simulation

Abstract

We present a parallel algorithm for molecular dynamics involving short-range two- and three-body potentials and the pair-correlation function, g(r). The method is based on a spatial decomposition of the simulation box that takes advantage of a linked-cell list, and allows a load balanced partition of the computations of both the forces and g(r) over the processors. The tests of the program is conducted by evaluating the efficiency for both the thermalization phase and the production phase of the simulation. This method is successfully applied to the calculation of the direct correlation function of fluid krypton at small scattering angle along the T = 297 K supercritical isotherm.     

A Molecular Dynamics Simulation Study of Rigid and Non-rigid Hard Dumb-bells

Abstract

We present a comparative study, using molecular dynamics, of systems of diatomic, hard dumb-bell, molecules in which the interatomic distance is either constrained to a fixed value or is allowed to vary freely between preset limits. A significant improvement in simulation effciency can be attained by allowing the bond length to vary. We find that thermodynamic properties, and some time correlation functions, are only slightly affected by the removal of the rigid bond-length constraint. The atomic velocity correlation function responds dramatically at short times to changes in the degree of non-rigidity, but at long times these differences are much less important.     

Molecular interaction of δ-conopeptide EVIA with voltage-gated Na+ channels

BackgroundFor a large number of conopeptides basic knowledge related to structure-activity relationships is unavailable although such information is indispensable with respect to drug development and their use as drug leads.MethodsA combined experimental and theoretical approach employing electrophysiology and molecular modeling was applied for identifying the conopeptide δ-EVIA binding site at voltage-gated Na⁺ channels and to gain insight into the toxin's mode of action.ResultsConopeptide δ-EVIA was synthesized and its structure was re-determined by NMR spectroscopy for molecular docking studies. Molecular docking and molecular dynamics simulation studies were performed involving the domain IV voltage sensor in a resting conformation and part of the domain I S5 transmembrane segment. Molecular modeling was stimulated by functional studies, which demonstrated the importance of domains I and IV of the neuronal Na_V1.7 channel for toxin action.Conclusionsδ-EVIA shares its binding epitope with other voltage-sensor toxins, such as the conotoxin δ-SVIE and various scorpion α-toxins. In contrast to previous in silico toxin binding studies, we present here in silico binding studies of a voltage-sensor toxin including the entire toxin binding site comprising the resting domain IV voltage sensor and S5 of domain I.General significanceThe prototypical voltage-sensor toxin δ-EVIA is suited for the elucidation of its binding epitope; in-depth analysis of its interaction with the channel target yields information on the mode of action and might also help to unravel the mechanism of voltage-dependent channel gating and coupling of activation and inactivation.     

Prevalent Mutations of Human Prion Protein: A Molecular Modeling and Molecular Dynamics Study

Abstract

Point mutations in the human prion protein gene, leading to amino acid substitutions in the human prion protein contribute to conversion of PrP^C to PrP^Sc and amyloid formation, resulting in prion diseases such as familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), and fatal familial insomnia. We have investigated impressions of prevalent mutations including Q217R, D202N, F198S, on the human prion protein and compared the mutant models with wild types. Structural analyses of models were performed with molecular modeling and molecular dynamics simulation methods. According to our results, frequently occurred mutations are observed in conserved and fully conserved sequences of human prion protein and the most fluctuation values occur in the Helix 1 around residues 144–152 and C-terminal end of the Helix 2. Our analysis of results obtained from MD simulation clearly shows that this long-range effect plays an important role in the conformational fluctuations in mutant structures of human prion protein. Results obtained from molecular modeling such as creation or elimination of some hydrogen bonds, increase or decrease of the accessible surface area and molecular surface, loss or accumulation of negative or positive charges on specific positions, and altering the polarity and pKa values, show that amino acid point mutations, though not urgently change the stability of PrP, might have some local impacts on the protein interactions which are required for oligomerization into fibrillar species.     

Investigations of Nematic-Isotropic Transition by Means of Constant Pressure Molecular Dynamics Simulations

Abstract

Constant pressure molecular dynamics simulations, which secure the system to be under hydrostatic pressure, are used to simulate the behavior of liquid crystals consisting of anisotropic molecules with both translational and orientational freedom. In order to investigate to what extent can the properties known to real liquid crystalline phases be explained by the anisotropy of the shape of the molecules alone, the molecular dynamic (MD) simulation uses purely repulsive short-range pair potentials representing soft spherocylinders. A clear change in the microscopic as well as the macroscopic physical properties are observed near the phase transition from nematic liquid crystal to isotropic liquid.     

MD Simulations of Liquids with Td,Oh Molecular Symmetry

Abstract

A new method is proposed for the calculation of intermolecular interactions in Molecular Dynamics simulations of liquids with T_d, O_h molecular symmetry. The new algorithm is based on the separation of the pair potential into a short-range and a long-range contribution described by a site-site and a spherical centre-centre potential model respectively using an additional cutoff distance. Test calculations for the Lennard-Jones fluids CCl₄ and SF₆ show significant savings in CPU time. We compare thermodynamic properties, pair correlation functions and a few dynamic autocorrelation functions obtained with the novel strategy with results of the commonly used algorithm for systems containing 864 molecules. Since no significant differences appear the new algorithm may be suggested as a useful contribution to the area of Molecular Dynamics simulation of liquids with these rather high molecular symmetries.     

Molecular Dynamics Simulation of Nucleation and Growth of a Binary Quasicrystal

Abstract

The quasicrystal structure is considered to be a new type of ordered phase because its Fourier transform has Laue spots with icosahedral symmetry, which is inconsistent with crystal structure. Computer simulation of the formation process of a quasicrystal was performed by the molecular dynamics method. On the basis of the Strandburg type of quasicrystal model, we developed an algorithm of the formation process of binary quasicrystal reflecting the procedure as realistically as possible. The Fourier transform of some of the obtained structures has shown decagonal symmetry although the spots are rather diffused. It has been shown that the potential parameter and experimental condition should be limited to produce a perfect quasicrystal structure.     

嗜热丁烷氧化古菌Candidatus Syntrophoarchaeum烷基转移酶MtaA催化丁基辅酶M的分子机制研究

【背景】嗜热古菌Candidatus Syntrophoarchaeum可以与硫酸盐还原细菌共生,通过逆转产甲烷途径进行正丁烷的氧化,但在该过程中负责催化丁基辅酶M氧化的酶尚未确定。【目的】利用分子动力学模拟证明Ca.Syntrophoarchaeum中mta A基因编码的蛋白可以特异性催化丁基辅酶M中丁基的转移,并非转移甲基。【方法】使用Methanosarcina mazei辅酶M甲基转移酶Mta A的晶体结构(PDB ID:4ay8)作为模板,对Mta A_1 (Gen Bank登录号OFV65993.1)和Mta A_2 (Gen Bank登录号OFV65678.1)进行同源建模。使用分子对接得到两者分别结合CH_3-Co M和C_4H_9-Co M时的结构,并用AMBER18进行分子动力学模拟。【结果】当Mta A_1和Mta A_2分别结合C_4H_9-Co M时,表现出与4ay8晶体结构类似的TIM-Barrel折叠三维结构,但在活性中心形状、Zn~(2+)与底物距离以及活性位点附近氨基酸配位方式等方面存在差异,这可能是导致Ca.Syntrophoarchaeum中mta A基因编码的蛋白催化丁基辅酶M氧化的原因。其中Mta A_2与4ay8结构更相似,活性中心氨基酸配位更完整,暗示其更可能具备催化活性。然而当Mta A_1和Mta A_2分别结合CH_3-Co M时,整体结构不合实际,活性中心Zn~(2+)与底物距离过远,表明底物几乎不可能与酶结合。【结论】Ca.Syntrophoarchaeum中的Mta A_1和Mta A_2很可能是特异性的丁基转移酶,而非催化甲基的转移,其中Mta A_2具备活性的可能性更高。     

An Application of Classical Molecular Dynamics Simulation and AB Initio Density-Functional Calculation in Surface Physics

Abstract

Classical molecular dynamics simulation and ab initio mixed basis Car-Parrinello methods are discussed and applied to the investigation of the results of a recently performed STM-based experiment involving the adsorption of C₆₀ molecules on the dimerized Si surface. We show that these methods are capable of providing the theoretical basis for this experiment and test the validity of the associated conjectures.

A mixed-basis all-electron formalism for the Car-Parrinello method is proposed to obtain the detailed understanding of the electronic states and dynamics of surface structure. A band structure calculation using this formalism is performed for the c(4 × 3) structure of C₆₀ adsorbed on Si (100) surface and is compared with the experimental results.     

Molecular insights of benzodipyrazole as CDK2 inhibitors: combined molecular docking,molecular dynamics,and 3D QSAR studies

Abstract

Benzodipyrazoles have been previously evaluated for their in vitro CDK2 inhibitory activity. In the current investigation, we identified a six-feature common pharmacophore model (AADDRR.33) which is predicted to be responsible for CDK2 inhibition. An efficient 3D QSAR (r^2?=?0.98 and q^2?=?0.82) model was also constructed by employing PLS regression analysis. From the molecular docking studies, we examined the binding patterns of compound 7aa with the target protein and also calculated the binding energy using MM-GBSA calculations. Three hydrogen bonds with Lys 33, Glu 81, and Leu 83 are conserved even after 1000?ps run in a molecular dynamics simulation. We identified the slight displacement in bond lengths and the conformational changes occurred during the dynamics. The results also elucidated the protein residue–ligand interaction fractions which clearly explained the involvement of non-H-bond interactions.