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This article is from PLoS ONE , volume 9 . Abstract In this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy and pharmacokinetics. Using computational docking, we predicted the structure of the complex between the antimalarial agent artemether and CYP2B6 whose conformations were obtained by MD simulation. The simulation demonstrated that the entire structure of the protein changes even when a single residue is mutated. Moreover, the structural flexibility is affected by the mutations and it may influence the enzyme activity. The results suggest that some of the inactive mutants cannot recognize artemether due to structural changes caused by the mutation.

This article is from PLoS ONE , volume 9 . Abstract In this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy and pharmacokinetics. Using computational docking, we predicted the structure of the complex between the antimalarial agent artemether and CYP2B6 whose conformations were obtained by MD simulation. The simulation demonstrated that the entire structure of the protein changes even when a single residue is mutated. Moreover, the structural flexibility is affected by the mutations and it may influence the enzyme activity. The results suggest that some of the inactive mutants cannot recognize artemether due to structural changes caused by the mutation.

This article is from Journal of Cheminformatics , volume 6 . Abstract None

This article is from FEBS Open Bio , volume 4 . Abstract

We present a simple and accurate computational method, which facilitates ab-initio path-integral molecular dynamics simulations, where the quantum mechanical nature of the nuclei is explicitly taken into account, at essentially no additional computational cost in comparison to the corresponding calculation using classical nuclei. The predictive power of the proposed quantum ring-polymer contraction method is demonstrated by computing various static and dynamic properties of liquid water at ambient conditions. This development permits to routinely include nuclear quantum effects in ab-initio molecular dynamics simulations.

This article is from International Journal of Molecular Sciences , volume 13 . Abstract Inhibition of p53-MDM2/MDMX interaction is considered to be a promising strategy for anticancer drug design to activate wild-type p53 in tumors. We carry out molecular dynamics (MD) simulations to study the binding mechanisms of peptide and non-peptide inhibitors to MDM2/MDMX. The rank of binding free energies calculated by molecular mechanics generalized Born surface area (MM-GBSA) method agrees with one of the experimental values. The results suggest that van der Waals energy drives two kinds of inhibitors to MDM2/MDMX. We also find that the peptide inhibitors can produce more interaction contacts with MDM2/MDMX than the non-peptide inhibitors. Binding mode predictions based on the inhibitor-residue interactions show that the π–π, CH–π and CH–CH interactions dominated by shape complimentarity, govern the binding of the inhibitors in the hydrophobic cleft of MDM2/MDMX. Our studies confirm the residue Tyr99 in MDMX can generate a steric clash with the inhibitors due to energy and structure. This finding may theoretically provide help to develop potent dual-specific or MDMX inhibitors.

An overview of Computational Dynamics: Dynamic Systems, Molecular Dynamics, Computational Sciences and Quantum Dynamics. Contents: Dynamical systems, in general Deterministic system (mathematics) Linear system Dynamical systems and chaos theory Chaos theory, Chaos argument, Butterfly effect, Bifurcation diagram, Feigenbaum constant, Sarkovskii's theorem, Attractor, Stability theory, Mechanical equilibrium Astable, Monostable, Bistable, Metastability, Feedback, Negative feedback Positive feedback Homeostasis Damping, Dissipative system, Spontaneous symmetry breaking, Turbulence, Perturbation theory Control theory: Non--linear control, Adaptive control, Hierarchical control, Intelligent control, Optimal control, Robust control, Stochastic control, System dynamics, System analysis, Takens' theorem Exponential dichotomy Lionard's theorem ;Dynamics Systems and Molecular Dynamics

We develop a novel method of replica-exchange molecular dynamics (REMD) simulation, mass-scaling REMD (MSREMD) method, which improves trajectory accuracy at high temperatures, and thereby contributes to numerical stability. In addition, the MSREMD method can also simplify a replica-exchange routine by eliminating velocity scaling. As a pilot system, a Lennard-Jones fluid is simulated with the new method. The results show that the MSREMD method improves the trajectory accuracy at high temperatures compared with the conventional REMD method. We analytically demonstrate that the MSREMD simulations can reproduce completely the same trajectories of the conventional REMD ones with shorter time steps at high temperatures in case of the Nos\'e-Hoover thermostats. Accordingly, we can easily compare the computational costs of the REMD and MSREMD simulations. We conclude that the MSREMD method decreases the instability and optimizes the computational resources with simpler algorithm under the constant trajectory accuracy at all temperatures.

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