title: A virtual-system coupled multicanonical molecular dynamics simulation: principles and applications to free-energy landscape of protein-protein interaction with an all-atom model in explicit solvent.
abstract: We propose a novel generalized ensemble method, a virtual-system coupled multicanonical molecular dynamics (V-McMD), to enhance conformational sampling of biomolecules expressed by an all-atom model in an explicit solvent. In this method, a virtual system, of which physical quantities can be set arbitrarily, is coupled with the biomolecular system, which is the target to be studied. This method was applied to a system of an Endothelin-1 derivative, KR-CSH-ET1, known to form an antisymmetric homodimer at room temperature. V-McMD was performed starting from a configuration in which two KR-CSH-ET1 molecules were mutually distant in an explicit solvent. The lowest free-energy state (the most thermally stable state) at room temperature coincides with the experimentally determined native complex structure. This state was separated to other non-native minor clusters by a free-energy barrier, although the barrier disappeared with elevated temperature. V-McMD produced a canonical ensemble faster than a conventional McMD method.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. higo@protein.osaka-u.ac.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Higo
authors.forename: Koji
authors.initials: K
authors.lastname: Umezawa
authors.forename: Haruki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D018360:Crystallography, X-Ray; D019332:Endothelin-1 / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012997:Solvents / Q000737:chemistry
chemical_list: D019332:Endothelin-1; D012997:Solvents