Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms

Biochim Biophys Acta. 2016 Jul;1858(7 Pt B):1635-51. doi: 10.1016/j.bbamem.2015.12.032. Epub 2016 Jan 5.

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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Algorithms*
  • Binding Sites
  • Cell Membrane / chemistry*
  • Cell Membrane / ultrastructure
  • Computer Simulation
  • Lipid Bilayers / chemistry*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / ultrastructure*
  • Models, Chemical
  • Models, Statistical
  • Molecular Dynamics Simulation*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping / methods

Substances

  • Lipid Bilayers
  • Membrane Proteins