Dr. Mark S. P. Sansom
Department of Biochemistry
University of Oxford
Oxford, England

Monday, August 22, 2005
3:00 pm (CT)
3269 Beckman Institute

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 will be described. Environments of membrane proteins that have been studied include: (i) solvent mixtures; (ii) detergent micelles; and (iii) lipid bilayers. Mixtures of water and non-aqueous solvents mimic a membrane via local clustering of solvent molecules to provide an anisotropic micro-environment for the protein. Detergent molecules exploit interaction sites on the protein surface that in vivo are occupied by lipid molecules. Simulations present a dynamic picture of protein interactions with annular lipids, and also can reveal more specific lipid interaction sites on the surfaces of membrane proteins. Comparison of simulations of KcsA (an _-helical bundle) and OmpA (a _-barrel) reveals the importance of two classes of sidechains in stabilizing interactions with the headgroups of lipid molecules: (i) Trp and Tyr; and (ii) Arg and Lys. 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. More recently it has proved possible to use MD simulations to look at larger scale dynamic events, such as self-assembly of protein/ detergent micelles.