Insertion and assembly of membrane proteins via simulation.
Interactions of lipids are central to the folding and stability of membrane proteins. Coarse-grained molecular dynamics simulations have been used to reveal the mechanisms of self-assembly of protein/membrane and protein/detergent complexes for representatives of two classes of membrane protein, namely, glycophorin (a simple alpha-helical bundle) and OmpA (a beta-barrel). The accuracy of the coarse-grained simulations is established via comparison with the equivalent atomistic simulations of self-assembly of protein/detergent micelles. The simulation of OmpA/bilayer self-assembly reveals how a folded outer membrane protein can be inserted in a bilayer. The glycophorin/bilayer simulation supports the two-state model of membrane folding, in which transmembrane helix insertion precedes dimer self-assembly within a bilayer. The simulations also suggest that a dynamic equilibrium exists between the glycophorin helix monomer and dimer within a bilayer. The simulated glycophorin helix dimer is remarkably close in structure to that revealed by NMR. Thus, coarse-grained methods may help to define mechanisms of membrane protein (re)folding and will prove suitable for simulation of larger scale dynamic rearrangements of biological membranes.
Department of Biochemistry, University of Oxford, UK.
Peter J
PJ
Bond
Mark S P
MS
Sansom
D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D006021:Glycophorins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008823:Micelles; D008956:Models, Chemical; D008958:Models, Molecular; D017433:Protein Structure, Secondary
D001425:Bacterial Outer Membrane Proteins; D006021:Glycophorins; D008051:Lipid Bilayers; D008823:Micelles; C078167:OMPA outer membrane proteins