title: Outer membrane proteins: comparing X-ray and NMR structures by MD simulations in lipid bilayers.
abstract: The structures of three bacterial outer membrane proteins (OmpA, OmpX and PagP) have been determined by both X-ray diffraction and NMR. We have used multiple (7 x 15 ns) MD simulations to compare the conformational dynamics resulting from the X-ray versus the NMR structures, each protein being simulated in a lipid (DMPC) bilayer. Conformational drift was assessed via calculation of the root mean square deviation as a function of time. On this basis the 'quality' of the starting structure seems mainly to influence the simulation stability of the transmembrane beta-barrel domain. Root mean square fluctuations were used to compare simulation mobility as a function of residue number. The resultant residue mobility profiles were qualitatively similar for the corresponding X-ray and NMR structure-based simulations. However, all three proteins were generally more mobile in the NMR-based than in the X-ray simulations. Principal components analysis was used to identify the dominant motions within each simulation. The first two eigenvectors (which account for >50% of the protein motion) reveal that such motions are concentrated in the extracellular loops and, in the case of PagP, in the N-terminal alpha-helix. Residue profiles of the magnitude of motions corresponding to the first two eigenvectors are similar for the corresponding X-ray and NMR simulations, but the directions of these motions correlate poorly reflecting incomplete sampling on a approximately 10 ns timescale.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Cox
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bond
authors.forename: Alessandro
authors.initials: A
authors.lastname: Grottesi
authors.forename: Marc
authors.initials: M
authors.lastname: Baaden
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D016062:Porosity; D025341:Principal Component Analysis; D017433:Protein Structure, Secondary
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008051:Lipid Bilayers; C078167:OMPA outer membrane proteins; D004134:Dimyristoylphosphatidylcholine