title: Molecular simulations and lipid-protein interactions: potassium channels and other membrane proteins.
abstract: Molecular dynamics simulations may be used to probe the interactions of membrane proteins with lipids and with detergents at atomic resolution. Examples of such simulations for ion channels and for bacterial outer membrane proteins are described. Comparison of simulations of KcsA (an alpha-helical bundle) and OmpA (a beta-barrel) reveals the importance of two classes of side chains in stabilizing interactions with the head groups of lipid molecules: (i) tryptophan and tyrosine; and (ii) arginine and lysine. Arginine residues interacting with lipid phosphate groups play an important role in stabilizing the voltage-sensor domain of the KvAP channel within a bilayer. Simulations of the bacterial potassium channel KcsA reveal specific interactions of phosphatidylglycerol with an acidic lipid-binding site at the interface between adjacent protein monomers. A combination of molecular modelling and simulation reveals a potential phosphatidylinositol 4,5-bisphosphate-binding site on the surface of Kir6.2.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. mark@biop.ox.ac.uk
authors.forename: M S P
authors.initials: MS
authors.lastname: Sansom
authors.forename: P J
authors.initials: PJ
authors.lastname: Bond
authors.forename: S S
authors.initials: SS
authors.lastname: Deol
authors.forename: A
authors.initials: A
authors.lastname: Grottesi
authors.forename: S
authors.initials: S
authors.lastname: Haider
authors.forename: Z A
authors.initials: ZA
authors.lastname: Sands
mesh_terms: D003198:Computer Simulation; D003902:Detergents; D008563:Membrane Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D015221:Potassium Channels / Q000737:chemistry*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry; D017433:Protein Structure, Secondary
chemical_list: D003902:Detergents; D008563:Membrane Lipids; D008565:Membrane Proteins; D008823:Micelles; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying