Recent Applications of Replica-Exchange Molecular Dynamics Simulations of Biomolecules

Yuji      Sugita; Naoyuki      Miyashita; Pai-Chi      Li; Takao      Yoda; Yuko      Okamoto

Abstract

Replica-exchange molecular dynamics (REMD) method is one of the enhanced conformational sampling techniques in MD simulations of proteins or other systems with rugged-energy landscapes. In REMD method, copies of original simulation system at different temperatures are simulated separately and simultaneously. Every few steps, temperatures between neighboring replicas are exchanged if the Metropolis criteria for their instantaneous potential energies are satisfied. Due to its simplicity and high efficiency in parallel computers, the method has been applied to many biological problems including protein folding, aggregation, receptor-ligand binding, and so on. In the last ten years, continuous effort to improve sampling efficiency of REMD simulations for larger biological systems has been carried out by us and other theoretical scientists. In this review article, we introduce two different approaches in REMD simulations to reduce the computational cost. One is the multicanonical replica-exchange method (MUCAREM) for reducing the number of replicas. In this method, each replica has a different multicanonical weight factor and takes a flat energy distribution to cover a wider potential energy space. Another approach is to employ implicit solvent/membrane models for representing surrounding environments of target proteins in REMD simulations. We show two applications of proteinfolding simulations in explicit solvent using the former approach and a structural prediction of a transmembrane protein dimer using the latter. Finally, we discuss possibilities of REMD method to simulate a large-scale conformational change of protein systems using massively parallel supercomputers.

Keywords: Amyloid precursor protein (APP), Aβ protein (Aβ), Implicit solvent/membrane model, Effective energy function 1 model (EEF1 model), Generalized-ensemble algorithm, Gly-XXX-Gly motif, Hamiltonian replica-exchange method, Histogram reweighting method, Hydrophobic core, Membrane protein, Multicanonical algorithm (MUCA), Multicanonical replicaexchange method (MUCAREM), Multi-dimensional replica-exchange method (MREM), Protein folding problem, Replicaexchange molecular dynamics method (REMD), Weighted histogram analysis method (WHAM)