title: Ligand docking simulations by generalized-ensemble algorithms.
abstract: In protein chemistry and structural biology, conventional simulations in physical statistical mechanical ensembles, such as the canonical ensemble with fixed temperature and isobaric-isothermal ensemble with fixed temperature and pressure, face a great difficulty. This is because there exist a huge number of local-minimum-energy states in the system and the conventional simulations tend to get trapped in these states, giving wrong results. Generalized-ensemble algorithms are based on artificial unphysical ensembles and overcome the above difficulty by performing random walks in potential energy, volume, and other physical quantities or their corresponding conjugate parameters such as temperature and pressure. The advantage of generalized-ensemble simulations lies in the fact that they not only avoid getting trapped in states of energy local minima but also allow the calculations of physical quantities as functions of temperature or other parameters from a single simulation run. In this chapter, we review the generalized-ensemble algorithms. Some of their specific examples such as replica-exchange molecular dynamics and replica-exchange umbrella sampling are described in detail. Examples of their applications to drug design are presented.
authors: Department of Physics, Graduate School of Science, Nagoya University, Nagoya, Japan; Structural Biology Research Center, Graduate School of Science, Nagoya University, Nagoya, Japan; Center for Computational Science, Graduate School of Engineering, Nagoya University, Nagoya, Japan; Information Technology Center, Nagoya University, Nagoya, Japan. Electronic address: okamoto@phys.nagoya-u.ac.jp.
authors: Yuko
authors: Y
authors: Okamoto
authors: Hironori
authors: H
authors: Kokubo
authors: Toshimasa
authors: T
authors: Tanaka
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D015195:Drug Design; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D013696:Temperature; D013816:Thermodynamics
keywords: Computer-aided drug design; Generalized-ensemble algorithm; Protein–ligand binding; Replica-exchange molecular dynamics; Replica-exchange umbrella sampling; Structure prediction