Molecular dynamics simulations:bring biomolecular structures alive on a computer

The molecular dynamics (MD) simulations play a very important role in science today. They have been used successfully in binding free-energy calculations and rational design of drugs and vaccines. MD simulations can help visualize and understand structures and dynamics at an atomistic level when combined with molecular graphics programs. The molecular and atomistic properties can be displayed on a computer in a time-dependent way, which opens a road toward a better understanding of the relationship of structure, dynamics, and function. In this chapter, the basics of MD are explained, together with a step-by-step description of setup and running an MD simulation.

Molecular dynamics simulations of the adsorption and diffusion behavior of pure and mixed alkanes in silicalite

The adsorption and diffusion of mixed hydrocarbon components in silicalite have been studied using molecular dynamic simulation methods. We have investigated the effect of molecular loadings and temperature on the diffusional behavior of both pure and mixed alkane components. For binary mixtures with components of similar sizes, molecular diffusional behavior in the channels was noticed to be reversed as loading is increased. This behavior was noticeably absent for components of different sizes in the mixture. Methane molecules in the methane/propane mixture have the highest diffusion coefficients across the entire loading range. Binary mixtures containing ethane molecules prove more difficult to separate compared to other binary components. In the ternary mixture, however, ethane molecules diffuse much faster at 400 K in the channel with a tendency to separate out quickly from other components. © 2005 Elsevier Inc. All rights reserved.

Monte Carlo and molecular dynamics simulations of methane in potassium montmorillonite clay hydrates at elevated pressures and temperatures

The structure and dynamics of methane in hydrated potassium montmorillonite clay have been studied under conditions encountered in sedimentary basin and compared to those of hydrated sodium montmorillonite clay using computer simulation techniques. The simulated systems contain two molecular layers of water and followed gradients of 150 barkm-1 and 30 Kkm-1 up to a maximum burial depth of 6 km. Methane particle is coordinated to about 19 oxygen atoms, with 6 of these coming from the clay surface oxygen. Potassium ions tend to move away from the center towards the clay surface, in contrast to the behavior observed with the hydrated sodium form. The clay surface affinity for methane was found to be higher in the hydrated K-form. Methane diffusion in the two-layer hydrated K-montmorillonite increases from 0.39×10-9 m2s-1 at 280 K to 3.27×10-9 m2s-1 at 460 K compared to 0.36×10-9 m2s-1 at 280 K to 4.26×10-9 m2s-1 at 460 K in Na-montmorillonite hydrate. The distributions of the potassium ions were found to vary in the hydrates when compared to those of sodium form. Water molecules were also found to be very mobile in the potassium clay hydrates compared to sodium clay hydrates. © 2004 Elsevier Inc. All All rights reserved.

Stress-induced platelet formation in silicon:a molecular dynamics study

The effect of stress on vacancy cluster configurations in silicon is examined using molecular dynamics. At zero pressure, the shape and stability of the vacancy clusters agrees with previous atomistic results. When stress is applied the orientation of small planar clusters changes to reduce the strain energy. The preferred orientation for the vacancy clusters under stress agrees with the experimentally observed orientations of hydrogen platelets in the high stress regions of hydrogen implanted silicon. These results suggest a theory for hydrogen platelet formation. © 2005 The American Physical Society.

Water network dynamics at the critical moment of a peptide's ß-turn formation:a molecular dynamics study

All-atom molecular dynamics simulations for a single molecule of Leu-Enkephalin in aqueous solution have been used to study the role of the water network during the formation of ß-turns. We give a detailed account of the intramolecular hydrogen bonding, the water-peptide hydrogen bonding, and the orientation and residence times of water molecules focusing on the short critical periods of transition to the stable ß-turns. These studies suggest that, when intramolecular hydrogen bonding between the first and fourth residue of the ß-turn is not present, the disruption of the water network and the establishment of water bridges constitute decisive factors in the formation and stability of the ß-turn. Finally, we provide possible explanations and mechanisms for the formations of different kinds of ß-turns.

Bridging large and small scales of water models using hybrid Molecular Dynamics/Fluctuating Hydrodynamics framework

This thesis presents a two-dimensional water model investigation and development of a multiscale method for the modelling of large systems, such as virus in water or peptide immersed in the solvent. We have implemented a two-dimensional ‘Mercedes Benz’ (MB) or BN2D water model using Molecular Dynamics. We have studied its dynamical and structural properties dependence on the model’s parameters. For the first time we derived formulas to calculate thermodynamic properties of the MB model in the microcanonical (NVE) ensemble. We also derived equations of motion in the isothermal–isobaric (NPT) ensemble. We have analysed the rotational degree of freedom of the model in both ensembles. We have developed and implemented a self-consistent multiscale method, which is able to communicate micro- and macro- scales. This multiscale method assumes, that matter consists of the two phases. One phase is related to micro- and the other to macroscale. We simulate the macro scale using Landau Lifshitz-Fluctuating Hydrodynamics, while we describe the microscale using Molecular Dynamics. We have demonstrated that the communication between the disparate scales is possible without introduction of fictitious interface or approximations which reduce the accuracy of the information exchange between the scales. We have investigated control parameters, which were introduced to control the contribution of each phases to the matter behaviour. We have shown, that microscales inherit dynamical properties of the macroscales and vice versa, depending on the concentration of each phase. We have shown, that Radial Distribution Function is not altered and velocity autocorrelation functions are gradually transformed, from Molecular Dynamics to Fluctuating Hydrodynamics description, when phase balance is changed. In this work we test our multiscale method for the liquid argon, BN2D and SPC/E water models. For the SPC/E water model we investigate microscale fluctuations which are computed using advanced mapping technique of the small scales to the large scales, which was developed by Voulgarakisand et. al.

Molecular dynamics simulation of brittle fracture in silicon

The fracture process involves converting potential energy from a strained body into surface energy, thermal energy, and the energy needed to create lattice defects. In dynamic fracture, energy is also initially converted into kinetic energy. This paper uses molecular dynamics (MD) to simulate brittle frcture in silicon and determine how energy is converted from potential energy (strain energy) into other forms.

Molecular dynamics simulation of methane in sodium montmorillonite clay hydrates at elevated pressures and temperatures

Computer simulation has been used to study the structure and dynamics of methane in hydrated sodium montmorillonite clays under conditions encountered in sedimentary basins. Systems containing approximately one, two, three and four molecular layers of water have followed gradients of 150 bar km-1 and 30Kkm-1, to a maximum burial depth of 6 km (900 bar and 460 K). Methane is coordinated to approximately 19 oxygen atoms, of which typically 6 are provided by the clay surface. Only in the three- and four-layer hydrates is methane able to leave the clay surface. Diffusion depends strongly on the porosity (water content) and burial depth: self-diffusion coefficients are in the range 0.12 × 10-9m2s-1 for water and 0.04 × 10−9m2s−1 < D < 8.64 × 10−9m2s−1 for methane. Bearing in mind that porosity decreases with burial depth, it is estimated that maximum diffusion occurs at around 3 km. This is in good agreement with the known location of methane reservoirs in sedimentary basins.

Large-scale molecular dynamics simulations of HLA-A*0201 complexed with a tumor-specific antigenic peptide:can the α3 and β2m domains be neglected?

Large-scale massively parallel molecular dynamics (MD) simulations of the human class I major histo-compatibility complex (MHC) protein HLA-A*0201 bound to a decameric tumor-specific antigenic peptide GVY-DGREHTV were performed using a scalable MD code on high-performance computing platforms. Such computational capabilities put us in reach of simulations of various scales and complexities. The supercomputing resources available Large-scale massively parallel molecular dynamics (MD) simulations of the human class I major histocompatibility complex (MHC) protein HLA-A*0201 bound to a decameric tumor-specific antigenic peptide GVYDGREHTV were performed using a scalable MD code on high-performance computing platforms. Such computational capabilities put us in reach of simulations of various scales and complexities. The supercomputing resources available for this study allow us to compare directly differences in the behavior of very large molecular models; in this case, the entire extracellular portion of the peptide–MHC complex vs. the isolated peptide binding domain. Comparison of the results from the partial and the whole system simulations indicates that the peptide is less tightly bound in the partial system than in the whole system. From a detailed study of conformations, solvent-accessible surface area, the nature of the water network structure, and the binding energies, we conclude that, when considering the conformation of the α1–α2 domain, the α3 and β2m domains cannot be neglected. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1803–1813, 2004

Molecular Dynamics implementation of BN2D or 'Mercedes Benz' water model

Two-dimensional 'Mercedes Benz' (MB) or BN2D water model (Naim, 1971) is implemented in Molecular Dynamics. It is known that the MB model can capture abnormal properties of real water (high heat capacity, minima of pressure and isothermal compressibility, negative thermal expansion coefficient) (Silverstein et al., 1998). In this work formulas for calculating the thermodynamic, structural and dynamic properties in microcanonical (NVE) and isothermal-isobaric (NPT) ensembles for the model from Molecular Dynamics simulation are derived and verified against known Monte Carlo results. The convergence of the thermodynamic properties and the system's numerical stability are investigated. The results qualitatively reproduce the peculiarities of real water making the model a visually convenient tool that also requires less computational resources, thus allowing simulations of large (hydrodynamic scale) molecular systems. We provide the open source code written in C/C++ for the BN2D water model implementation using Molecular Dynamics.

Histidine hydrogen bonding in MHC at pH 5 and pH 7 modeled by molecular docking and molecular dynamics simulations

Hydrogen bonds play important roles in maintaining the structure of proteins and in the formation of most biomolecular protein-ligand complexes. All amino acids can act as hydrogen bond donors and acceptors. Among amino acids, Histidine is unique, as it can exist in neutral or positively charged forms within the physiological pH range of 5.0 to 7.0. Histidine can thus interact with other aromatic residues as well as forming hydrogen bonds with polar and charged residues. The ability of His to exchange a proton lies at the heart of many important functional biomolecular interactions, including immunological ones. By using molecular docking and molecular dynamics simulation, we examine the influence of His protonation/deprotonation on peptide binding affinity to MHC class II proteins from locus HLA-DP. Peptide-MHC interaction underlies the adaptive cellular immune response, upon which the next generation of commercially-important vaccines will depend. Consistent with experiment, we find that peptides containing protonated His residues bind better to HLA-DP proteins than those with unprotonated His. Enhanced binding at pH 5.0 is due, in part, to additional hydrogen bonds formed between peptide His+ and DP proteins. In acidic endosomes, protein His79β is predominantly protonated. As a result, the peptide binding cleft narrows in the vicinity of His79β, which stabilizes the peptide - HLA-DP protein complex. © 2014 Bentham Science Publishers.

Multiscale molecular dynamics/hydrodynamics implementation of two dimensional “Mercedes Benz” water model

A multiscale Molecular Dynamics/Hydrodynamics implementation of the 2D Mercedes Benz (MB or BN2D) [1] water model is developed and investigated. The concept and the governing equations of multiscale coupling together with the results of the two-way coupling implementation are reported. The sensitivity of the multiscale model for obtaining macroscopic and microscopic parameters of the system, such as macroscopic density and velocity fluctuations, radial distribution and velocity autocorrelation functions of MB particles, is evaluated. Critical issues for extending the current model to large systems are discussed.

A hybrid molecular dynamics/fluctuating hydrodynamics method for modelling liquids at multiple scales in space and time

A new 3D implementation of a hybrid model based on the analogy with two-phase hydrodynamics has been developed for the simulation of liquids at microscale. The idea of the method is to smoothly combine the atomistic description in the molecular dynamics zone with the Landau-Lifshitz fluctuating hydrodynamics representation in the rest of the system in the framework of macroscopic conservation laws through the use of a single "zoom-in" user-defined function s that has the meaning of a partial concentration in the two-phase analogy model. In comparison with our previous works, the implementation has been extended to full 3D simulations for a range of atomistic models in GROMACS from argon to water in equilibrium conditions with a constant or a spatially variable function s. Preliminary results of simulating the diffusion of a small peptide in water are also reported.

Computational mechanics of molecular systems:quantifying high-dimensional dynamics by distribution of Poincaré recurrence times

A framework that connects computational mechanics and molecular dynamics has been developed and described. As the key parts of the framework, the problem of symbolising molecular trajectory and the associated interrelation between microscopic phase space variables and macroscopic observables of the molecular system are considered. Following Shalizi and Moore, it is shown that causal states, the constituent parts of the main construct of computational mechanics, the e-machine, define areas of the phase space that are optimal in the sense of transferring information from the micro-variables to the macro-observables. We have demonstrated that, based on the decay of their Poincare´ return times, these areas can be divided into two classes that characterise the separation of the phase space into resonant and chaotic areas. The first class is characterised by predominantly short time returns, typical to quasi-periodic or periodic trajectories. This class includes a countable number of areas corresponding to resonances. The second class includes trajectories with chaotic behaviour characterised by the exponential decay of return times in accordance with the Poincare´ theorem.

Complexity of classical dynamics of molecular systems. II. Finite statistical complexity of a water-Na+ system

The computational mechanics approach has been applied to the orientational behavior of water molecules in a molecular dynamics simulated water–Na + system. The distinctively different statistical complexity of water molecules in the bulk and in the first solvation shell of the ion is demonstrated. It is shown that the molecules undergo more complex orientational motion when surrounded by other water molecules compared to those constrained by the electric field of the ion. However the spatial coordinates of the oxygen atom shows the opposite complexity behavior in that complexity is higher for the solvation shell molecules. New information about the dynamics of water molecules in the solvation shell is provided that is additional to that given by traditional methods of analysis.