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.
Bond
Peter J
PJ
Department of Biochemistry, University of Oxford, UK.
Sansom
Mark S P
MS
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