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

Stansfeld PJ, Goose JE, Caffrey M, Carpenter EP, Parker JL, Newstead S, Sansom MS - Structure (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

No MeSH data available.


Related in: MedlinePlus

A Database of Membrane Proteins in Phospholipid Bilayers(A) Snapshots of the final (i.e., 1 μs) configurations of 2,294 membrane proteins in a phospholipid (PC) bilayer.(B) Zoomed-in representation of the 5-HT3 ligand-gated ion channel (PDB: 4PIR; pentameric asymmetric unit and biological assembly) in a PC bilayer. Lipid headgroups are shown as spheres representing the choline (blue), phosphate (red), and glycerol (yellow) particles of the CG model. See also Figure S2.
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fig2: A Database of Membrane Proteins in Phospholipid Bilayers(A) Snapshots of the final (i.e., 1 μs) configurations of 2,294 membrane proteins in a phospholipid (PC) bilayer.(B) Zoomed-in representation of the 5-HT3 ligand-gated ion channel (PDB: 4PIR; pentameric asymmetric unit and biological assembly) in a PC bilayer. Lipid headgroups are shown as spheres representing the choline (blue), phosphate (red), and glycerol (yellow) particles of the CG model. See also Figure S2.

Mentions: Within the 2,294 identified structures there are 1,991 α-helical and 303 β-barrel proteins in MemProtMD, corresponding to 503 α-helical and 125 β-barrel unique membrane protein structures (Figure 2A; Figure S2). This updates the 533 unique structures, as annotated by mpstruc (http://blanco.biomol.uci.edu/mpstruc/) (White, 2009). Each entry in the dataset provides the coordinates of the first biological assembly in the PDB of the protein embedded in a PC lipid bilayer in both CG and AT representations (Figure 2B). The CG simulations associated with each entry (1 μs of CGMD in a bilayer) provide the basis for initial analysis of the protein/lipid interactions of a given membrane protein. Such interactions may also provide insights into membrane protein function, especially when a protein is known to interact with lipid-like ligands. Each entry also provides an initial setup for more detailed ATMD simulations to explore conformational dynamics of membrane proteins in relation to their mechanism of action. As a whole, the dataset provides the basis for more global analyses of membrane protein/bilayer interactions, including the propensities of each amino acid side-chain type to be located at a given position relative to the bilayer. In turn, local deviations from the global average distribution of side chains can provide pointers to key functional and structural aspects of the structure and function of the membrane protein. Finally, simulations based on individual entries may aid in evaluation and refinement of membrane protein structures.


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

Stansfeld PJ, Goose JE, Caffrey M, Carpenter EP, Parker JL, Newstead S, Sansom MS - Structure (2015)

A Database of Membrane Proteins in Phospholipid Bilayers(A) Snapshots of the final (i.e., 1 μs) configurations of 2,294 membrane proteins in a phospholipid (PC) bilayer.(B) Zoomed-in representation of the 5-HT3 ligand-gated ion channel (PDB: 4PIR; pentameric asymmetric unit and biological assembly) in a PC bilayer. Lipid headgroups are shown as spheres representing the choline (blue), phosphate (red), and glycerol (yellow) particles of the CG model. See also Figure S2.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4509712&req=5

fig2: A Database of Membrane Proteins in Phospholipid Bilayers(A) Snapshots of the final (i.e., 1 μs) configurations of 2,294 membrane proteins in a phospholipid (PC) bilayer.(B) Zoomed-in representation of the 5-HT3 ligand-gated ion channel (PDB: 4PIR; pentameric asymmetric unit and biological assembly) in a PC bilayer. Lipid headgroups are shown as spheres representing the choline (blue), phosphate (red), and glycerol (yellow) particles of the CG model. See also Figure S2.
Mentions: Within the 2,294 identified structures there are 1,991 α-helical and 303 β-barrel proteins in MemProtMD, corresponding to 503 α-helical and 125 β-barrel unique membrane protein structures (Figure 2A; Figure S2). This updates the 533 unique structures, as annotated by mpstruc (http://blanco.biomol.uci.edu/mpstruc/) (White, 2009). Each entry in the dataset provides the coordinates of the first biological assembly in the PDB of the protein embedded in a PC lipid bilayer in both CG and AT representations (Figure 2B). The CG simulations associated with each entry (1 μs of CGMD in a bilayer) provide the basis for initial analysis of the protein/lipid interactions of a given membrane protein. Such interactions may also provide insights into membrane protein function, especially when a protein is known to interact with lipid-like ligands. Each entry also provides an initial setup for more detailed ATMD simulations to explore conformational dynamics of membrane proteins in relation to their mechanism of action. As a whole, the dataset provides the basis for more global analyses of membrane protein/bilayer interactions, including the propensities of each amino acid side-chain type to be located at a given position relative to the bilayer. In turn, local deviations from the global average distribution of side chains can provide pointers to key functional and structural aspects of the structure and function of the membrane protein. Finally, simulations based on individual entries may aid in evaluation and refinement of membrane protein structures.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

No MeSH data available.


Related in: MedlinePlus