A Generic Force Field for Protein Coarse-Grained Molecular Dynamics Simulation

Junfeng Gu,Fang Bai,Xicheng Wang,Honglin Li

doi:10.3390/ijms131114451

Abstract

Coarse-grained (CG) force fields have become promising tools for studies of protein behavior, but the balance of speed and accuracy is still a challenge in the research of protein coarse graining methodology. In this work, 20 CG beads have been designed based on the structures of amino acid residues, with which an amino acid can be represented by one or two beads, and a CG solvent model with five water molecules was adopted to ensure the consistence with the protein CG beads. The internal interactions in protein were classified according to the types of the interacting CG beads, and adequate potential functions were chosen and systematically parameterized to fit the energy distributions. The proposed CG force field has been tested on eight proteins, and each protein was simulated for 1000 ns. Even without any extra structure knowledge of the simulated proteins, the Cα root mean square deviations (RMSDs) with respect to their experimental structures are close to those of relatively short time all atom molecular dynamics simulations. However, our coarse grained force field will require further refinement to improve agreement with and persistence of native-like structures. In addition, the root mean square fluctuations (RMSFs) relative to the average structures derived from the simulations show that the conformational fluctuations of the proteins can be sampled.

Highlights

Over the last 30 years, the Molecular Dynamics (MD) method has played an increasing important role in dynamic behavior simulation of biomolecule at the atomic level [1]
We report in our recent work on the improvement of Coarse-Grained Molecular Dynamics (CG-MD) methodology
When we made the statistical analyses of the distance distributions between two ALA amino acids on the above-mentioned protein structure database, the probability peak corresponding to the energy minimum was found around 0.55 nm

Summary

Introduction

Over the last 30 years, the Molecular Dynamics (MD) method has played an increasing important role in dynamic behavior simulation of biomolecule at the atomic level [1]. In numerous application areas such as structural biology, biophysics, biochemistry, enzymology, molecular biology and medicinal chemistry, etc., MD has become a major routine research tool. By means of MD simulation, biomolecular structure, kinetics, and thermodynamics can be investigated, for example, macromolecular stability, conformational and allosteric properties, the role of dynamics in enzyme activity, molecular recognition and the properties of complexes, ion and small molecule transport, protein association, protein folding, and protein hydration [2]. With the development of modern computer technology, high performance computing and molecular dynamics method, the application of AA-MD has made great progresses in both space scale and time scale. AA-MD still cannot meet all the need of biomolecule research

Methods

Results

Conclusion