Surface-Tension Replica-Exchange Molecular Dynamics Method for Efficient Conformational Sampling of Biological Membrane Systems

Abstract

Conformational sampling is fundamentally important for simulating complex bio-molecular systems. Generalized-ensemble algorithm, especially the temperature replica-exchange molecular dynamics method (REMD), is one of the widely used methods to explore structures of bio-molecules. Most temperature REMD simulations have focused on soluble proteins rather than membrane proteins or lipid bilayers, because explicit membranes do not keep their structural integrity at high temperature. Here, we propose a new generalized-ensemble algorithm for membrane systems, which we call the surface-tension REMD method. Each replica is simulated in the NPγT ensemble, where surface tensions in a pair of replicas are exchanged at certain intervals to enhance conformational sampling of the target membrane system. We tested our method on a fully hydrated DPPC lipid bilayer. During the simulation, a random walk in surface tension space is realized. Large-scale lateral deformation of DPPC membranes takes place in all of the replicas without collapse of the lipid bilayer structure. Our method could be applicable to a wide variety of biological membrane systems including mixed lipid bilayers and membrane-protein systems.