Molecular dynamics simulations of proteins in lipid bilayers

Abstract

With recent advances in X-ray crystallography of membrane proteins promising many new high-resolution structures, molecular dynamics simulations will become increasingly valuable for understanding membrane protein function, as they can reveal the dynamic behavior concealed in the static structures. Dramatic increases in computational power, in synergy with more efficient computational methodologies, now allow us to carry out molecular dynamics simulations of any structurally known membrane protein in its native environment, covering timescales of up to 0.1 micros. At the frontiers of membrane protein simulations are ion channels, aquaporins, passive and active transporters, and bioenergetic proteins.

Figure 1

Some membrane proteins that have been recently studied by molecular dynamics, presented against a lipid bilayer background. From left to right: bacteriorhodopsin, the K⁺ channel KcsA, the aquaporin GlpF, the porin OmpF, and the mechanosensitive channel MscS.

Figure 2

Computing the current/voltage dependence of a membrane channel with all-atom molecular dynamics. (a) A microscopic model of a membrane channel is constructed. (b) In an MD simulation, a transmembrane potential is generated by applying an external electric field. (c) The current is computed by tracing local displacements of the ions. Repeating the simulation at different applied fields yields the current/voltage dependence.