Insertion and assembly of membrane proteins via simulation.

Journal article

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.

Authors: Bond, P; Sansom, MS

• Publication status: Published
• Journal: Journal of the American Chemical Society
• Volume: 128
• Issue: 8
• Pages: 2697-2704
• Publication date: 2006-03-01
• DOI: 10.1021/ja0569104
• EISSN: 1520-5126
• ISSN: 0002-7863
• Language: English
• Keywords: Bacterial Outer Membrane Proteins; Lipid Bilayers; Protein Structure, Secondary; Glycophorin; Models, Chemical; Kinetics; Computer Simulation; Models, Molecular; Micelles