title: MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes.
abstract: There has been exponential growth in the number of membrane protein structures determined. Nevertheless, these structures are usually resolved in the absence of their lipid environment. Coarse-grained molecular dynamics (CGMD) simulations enable insertion of membrane proteins into explicit models of lipid bilayers. We have automated the CGMD methodology, enabling membrane protein structures to be identified upon their release into the PDB and embedded into a membrane. The simulations are analyzed for protein-lipid interactions, identifying lipid binding sites, and revealing local bilayer deformations plus molecular access pathways within the membrane. The coarse-grained models of membrane protein/bilayer complexes are transformed to atomistic resolution for further analysis and simulation. Using this automated simulation pipeline, we have analyzed a number of recently determined membrane protein structures to predict their locations within a membrane, their lipid/protein interactions, and the functional implications of an enhanced understanding of the local membrane environment of each protein.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stansfeld
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Goose
authors.affiliation: Schools of Medicine and Biochemistry & Immunology, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: Caffrey
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Elisabeth P
authors.initials: EP
authors.lastname: Carpenter
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Parker
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Newstead
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: mark.sansom@bioch.ox.ac.uk.
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D001665:Binding Sites; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins