Folding and Assembly of Membrane Proteins: Coarse Grained Molecular Dynamics Simulations of EmrE

Abstract

EmrE is a bacterial drug resistance transporter, from E. coli. It is believed to function as an antiparallel homodimer, each monomer of which contains four transmembrane helices. Coarse-grained molecular dynamics (CG-MD) simulations have been previously used to study the insertion and self-assembly of transmembrane helices, and the formation of transmembrane helix dimers and tetramers in lipid bilayers. Such simulations have used a local modification of the original Marrink CG forcefield [1]. In the current study, these methods are employed to investigate the folding and self-assembly of EmrE. Self-assembly CG-MD simulations of the isolated helices of EmrE suggest that each of the constituent helices inserts into a phosphatidylcholine bilayer to adopt a transmembrane orientation. Helix hairpins and other fragments have been simulated to explore the self-assembly and folding processes of the protein subsequent to helix insertion. Simulations of parallel vs. anti-parallel pairs of EmrE monomers are used to explore formation and stability of the EmrE dimer.(1) Bond, P.J., Wee, C.L., and Sansom, M.S.P. (2008) Coarse-grained molecular dynamics simulations of the energetics of helix insertion into a lipid bilayer. Biochem. (in press), bi-2008-00642m.R1.