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R.A. Böckmann; A. Caflisch

Journal: Biophys. J.
Year: 2005
Volume: 88
Issue: 5
Pages: 3191-3204
DOI: 10.1529/biophysj.105.060426
Type of Publication: Journal Article

Bacterial Outer Membrane Proteins; Computer Simulation; Detergents; Escherichia coli; Escherichia coli Proteins; Hydrolases; Lipids; Magnetic Resonance Spectroscopy; Micelles; Models, Molecular; Models, Statistical; Phosphatidylcholines; Phospholipid Ethers; Protein Binding; Protein Conformation; Protein Structure, Secondary; Proteins; Solvents; Surface Properties; Time Factors; Water


The structure and flexibility of the outer membrane protein X (OmpX) in a water-detergent solution and in pure water are investigated by molecular dynamics simulations on the 100-ns timescale and compared with NMR data. The simulations allow for an unbiased determination of the structure of detergent micelles and the protein-detergent mixed micelle. The short-chain lipid dihexanoylphosphatidylcholine, as a detergent, aggregates into pure micelles of approximately 18 molecules, or alternatively, it binds to the protein surface. The detergent binds in the form of a monolayer ring around the hydrophobic β-barrel of OmpX rather than in a micellar-like oblate; approximately 40 dihexanoylphosphatidylcholine lipids are sufficient for an effective suppression of water from the surface of the beta-barrel region. The phospholipids bind also on the extracellular, protruding β-sheet. Here, polar interactions between charged amino acids and phosphatidylcholine headgroups act as condensation seed for detergent micelle formation. The polar protein surface remains accessible to water molecules. In total, approximately 90-100 detergent molecules associate within the protein-detergent mixed micelle, in agreement with experimental estimates. The simulation results indicate that OmpX is not a water pore and support the proposed role of the protruding β-sheet as a "fishing rod".