title: Extended Phase-Space Methods for Enhanced Sampling in Molecular Simulations: A Review.
abstract: Molecular Dynamics simulations are a powerful approach to study biomolecular conformational changes or protein-ligand, protein-protein, and protein-DNA/RNA interactions. Straightforward applications, however, are often hampered by incomplete sampling, since in a typical simulated trajectory the system will spend most of its time trapped by high energy barriers in restricted regions of the configuration space. Over the years, several techniques have been designed to overcome this problem and enhance space sampling. Here, we review a class of methods that rely on the idea of extending the set of dynamical variables of the system by adding extra ones associated to functions describing the process under study. In particular, we illustrate the Temperature Accelerated Molecular Dynamics (TAMD), Logarithmic Mean Force Dynamics (LogMFD), and Multiscale Enhanced Sampling (MSES) algorithms. We also discuss combinations with techniques for searching reaction paths. We show the advantages presented by this approach and how it allows to quickly sample important regions of the free-energy landscape via automatic exploration.
authors.affiliation: Department of Physics, Nippon Medical School , Tokyo , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujisaki
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University , Yokohama , Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Moritsugu
authors.affiliation: Advanced Institute for Computational Science , Kobe , Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST) , Tsukuba , Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Morishita
authors.affiliation: Center for Synaptic Neuroscience, Istituto Italiano di Tecnologia , Genova , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Maragliano
keywords: biomolecular interactions; conformational transitions; free energy; molecular dynamics; protein–ligand binding; rare events