title: Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms.
abstract: This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
authors.affiliation: iTHES Research Group and Theoretical Molecular Science Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Mori
authors.affiliation: Laboratory for Biomolecular Function Simulation, RIKEN Quantitative Biology Center, Integrated Innovation Building 7F, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Faculty of Biology-Oriented Science and Technology, KINDAI University, 930 Nishimitani, Kinokawa, Wakayama 649-6493, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyashita
authors.affiliation: Department of Molecular Sciences and Center for Computational Biology, The University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, United States.
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
authors.affiliation: Laboratory for Biomolecular Function Simulation, RIKEN Quantitative Biology Center, Integrated Innovation Building 7F, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, United States; Department of Chemistry, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Feig
authors.affiliation: iTHES Research Group and Theoretical Molecular Science Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Laboratory for Biomolecular Function Simulation, RIKEN Quantitative Biology Center, Integrated Innovation Building 7F, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Department of Chemistry, Michigan State University, East Lansing, MI 48824, United States; Computational Biophysics Research Team, RIKEN Advanced Institute for Computational Science, 7-1-26 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: sugita@riken.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D015233:Models, Statistical; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins
keywords: Generalized Born (GB) model; Generalized-ensemble algorithm; Replica exchange with solute tempering (REST); Replica-exchange molecular dynamics (REMD); Replica-exchange umbrella sampling (REUS); Surface-tension REMD