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PMID: 26073602 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes.

Structure (London, England : 1993) ·Vol. 23 ·No. 7 ·2015-07-07 ·Pages 1350-61

Stansfeld PJ, Goose JE, Caffrey M, Carpenter EP, Parker JL, Newstead S, Sansom MS

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.

MeSH Terms
Binding Sites Hydrophobic and Hydrophilic Interactions Lipid Bilayers/chemistry Membrane Proteins/chemistry Molecular Dynamics Simulation Protein Conformation
Chemicals
Lipid Bilayers Membrane Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Stansfeld Phillip J
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Goose Joseph E
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Caffrey Martin
Schools of Medicine and Biochemistry & Immunology, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
Carpenter Elisabeth P
Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
Parker Joanne L
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Newstead Simon
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Sansom Mark S P
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: mark.sansom@bioch.ox.ac.uk.
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
1878-4186
DOI
10.1016/j.str.2015.05.006
Email
mark.sansom@bioch.ox.ac.uk
Published
2015-07-07
Epub
2015-00-11
Pages
1350-61
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC4509712
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · BB/L002558/1 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/I019855/1 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBS/B/16011 · United Kingdom
Biotechnology and Biological Sciences Research Council · BEP17032 · United Kingdom
Wellcome Trust · 102890/Z/13/Z · United Kingdom
Medical Research Council · G0900399 · United Kingdom
Biotechnology and Biological Sciences Research Council · B19456 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/H000267/1 · United Kingdom
Wellcome Trust · 106169 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/L002531/1 · United Kingdom
Wellcome Trust · 084655 · United Kingdom
Wellcome Trust · 102890 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.str.2015.05.006 PMC Full Text View journal details
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