A Database of Inserted Membrane Proteins.
Dr Peter J. Bond, Alan P. Chetwynd, Dr Kathryn A. Scott & Prof Mark S.P. Sansom

Many biophysical studies indicate interactions with lipid/detergent molecules are critical to the folding/stability of membrane proteins, but only limited structural data are available on these interactions. In principle, molecular dynamics (MD) simulations may be used to follow the self-assembly of proteins with lipid/detergent. However, MD studies are limited to system sizes of up to ~100,000 atoms and time lengths of up to ~100 ns. Coarse grained (CG) models, in which small groups of atoms are treated collectively as large particles, provide a method for increasing timescales and system dimensions.

BtuCD

A recent model for semi-quantitative lipid simulations has been developed by SJ Marrink (see his website) for the GROMACS simulation package. We have adapted this model to allow the simulation of membrane proteins (as described in Bond & Sansom (2006), J. Am. Chem. Soc.), in particular applied to the insertion of proteins into lipid bilayers or detergent micelles. This has proved to be successful in reproducing the behaviour of equivalent atomistic simulations of model proteins, as well as allowing the insertion of various test peptides whose final configurations were in agreement with experimental data. We have subsequently applied this method to the automated insertion into bilayers of membrane proteins obtained at medium- to high-resolution, using the following protocol:

» Surround protein with randomly placed DPPC lipids and solvent
» Carry out minimum of 200 ns of MD using GROMACS
» Extract snapshot of each protein in its optimum position within bilayer
» Submit to database: simulation properties/snapshots, final system coordinates, and analysis of lipid-protein interactions

This work has been supported by:

» Dr Syma Khalid and Tony Ivetac (analysis of lipid-protein interaction, database design)
» Dr Phil Biggin, John Holyoake, Dr Kia Balali-Mood, Chze-Ling Wee, Chee Foong Chew, Ben Hall (refinement of methodology)
» Shiva Amiri, Tim Carpenter, Emi Psachoulia (testing)


If you use data from this website in your research please cite:

» Mark S.P. Sansom*, Kathryn A. Scott and Peter J. Bond. Coarse Grained Simulation: A High Throughput Computational Approach To Membrane Proteins. Biochem. Soc. Trans. In press


Structural Bioinformatics & Computational Biochemistry, University of Oxford.