Enhanced sampling simulations to construct free-energy landscape of protein-partner substrate interaction

タンパク質-基質相互作用の自由エネルギー地形構築のための拡張サンプリングシミュレーション

池部 仁善; 梅澤 公二*; 肥後 順一*

Ikebe, Kimiyoshi; Umezawa, Koji*; Higo, Junichi*

Molecular dynamics (MD) simulations with both of all-atom and explicit solvent models provide the detailed behavior of protein-partner substrate binding at the atomic level. As the power of computational resources rise, MD simulations are being used more widely and easily. However it is still difficult to investigate thermodynamic properties of protein-partner substrate binding as well as protein folding with conventional MD simulations. Enhanced sampling methods have been developed to sample conformations reflecting equilibrium conditions in a more efficient manner than conventional MD simulations allowing the construction of accurate free energy landscapes. In this review, we discuss these enhanced sampling methods using a series of case by case examples. In particular we review enhanced sampling methods conforming to trivial trajectory parallelization (TTP), virtual-system coupled McMD (V-McMD), and adaptive lambda square dynamics (ALSD). These methods have been recently developed based on the existing method of multicanonical MD (McMD) simulation. Their applications are reviewed with an emphasis on describing their practical implementation. In our concluding remarks we explore extensions of the enhanced sampling methods that may allow for even more efficient sampling.