Coarse-grained molecular dynamics simulations of membrane proteins and peptides.
Molecular dynamics (MD) simulations provide a valuable approach to the dynamics, structure, and stability of membrane-protein systems. Coarse-grained (CG) models, in which small groups of atoms are treated as single particles, enable extended (>100 ns) timescales to be addressed. In this stud...
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| Fformat: | Journal article |
| Iaith: | English |
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2007
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| _version_ | 1826286655531646976 |
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| author | Bond, P Holyoake, J Ivetac, A Khalid, S Sansom, MS |
| author_facet | Bond, P Holyoake, J Ivetac, A Khalid, S Sansom, MS |
| author_sort | Bond, P |
| collection | OXFORD |
| description | Molecular dynamics (MD) simulations provide a valuable approach to the dynamics, structure, and stability of membrane-protein systems. Coarse-grained (CG) models, in which small groups of atoms are treated as single particles, enable extended (>100 ns) timescales to be addressed. In this study, we explore how CG-MD methods that have been developed for detergents and lipids may be extended to membrane proteins. In particular, CG-MD simulations of a number of membrane peptides and proteins are used to characterize their interactions with lipid bilayers. CG-MD is used to simulate the insertion of synthetic model membrane peptides (WALPs and LS3) into a lipid (PC) bilayer. WALP peptides insert in a transmembrane orientation, whilst the LS3 peptide adopts an interfacial location, both in agreement with experimental biophysical data. This approach is extended to a transmembrane fragment of the Vpu protein from HIV-1, and to the coat protein from fd phage. Again, simulated protein/membrane interactions are in good agreement with solid state NMR data for these proteins. CG-MD has also been applied to an M3-M4 fragment from the CFTR protein. Simulations of CFTR M3-M4 in a detergent micelle reveal formation of an alpha-helical hairpin, consistent with a variety of biophysical data. In an I231D mutant, the M3-M4 hairpin is additionally stabilized via an inter-helix Q207/D231 interaction. Finally, CG-MD simulations are extended to a more complex membrane protein, the bacterial sugar transporter LacY. Comparison of a 200 ns CG-MD simulation of LacY in a DPPC bilayer with a 50 ns atomistic simulation of the same protein in a DMPC bilayer shows that the two methods yield comparable predictions of lipid-protein interactions. Taken together, these results demonstrate the utility of CG-MD simulations for studies of membrane/protein interactions. |
| first_indexed | 2024-03-07T01:46:58Z |
| format | Journal article |
| id | oxford-uuid:98bd6b5d-7af9-417e-9188-1fec4e106d0e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:46:58Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:98bd6b5d-7af9-417e-9188-1fec4e106d0e2022-03-27T00:09:10ZCoarse-grained molecular dynamics simulations of membrane proteins and peptides.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:98bd6b5d-7af9-417e-9188-1fec4e106d0eEnglishSymplectic Elements at Oxford2007Bond, PHolyoake, JIvetac, AKhalid, SSansom, MSMolecular dynamics (MD) simulations provide a valuable approach to the dynamics, structure, and stability of membrane-protein systems. Coarse-grained (CG) models, in which small groups of atoms are treated as single particles, enable extended (>100 ns) timescales to be addressed. In this study, we explore how CG-MD methods that have been developed for detergents and lipids may be extended to membrane proteins. In particular, CG-MD simulations of a number of membrane peptides and proteins are used to characterize their interactions with lipid bilayers. CG-MD is used to simulate the insertion of synthetic model membrane peptides (WALPs and LS3) into a lipid (PC) bilayer. WALP peptides insert in a transmembrane orientation, whilst the LS3 peptide adopts an interfacial location, both in agreement with experimental biophysical data. This approach is extended to a transmembrane fragment of the Vpu protein from HIV-1, and to the coat protein from fd phage. Again, simulated protein/membrane interactions are in good agreement with solid state NMR data for these proteins. CG-MD has also been applied to an M3-M4 fragment from the CFTR protein. Simulations of CFTR M3-M4 in a detergent micelle reveal formation of an alpha-helical hairpin, consistent with a variety of biophysical data. In an I231D mutant, the M3-M4 hairpin is additionally stabilized via an inter-helix Q207/D231 interaction. Finally, CG-MD simulations are extended to a more complex membrane protein, the bacterial sugar transporter LacY. Comparison of a 200 ns CG-MD simulation of LacY in a DPPC bilayer with a 50 ns atomistic simulation of the same protein in a DMPC bilayer shows that the two methods yield comparable predictions of lipid-protein interactions. Taken together, these results demonstrate the utility of CG-MD simulations for studies of membrane/protein interactions. |
| spellingShingle | Bond, P Holyoake, J Ivetac, A Khalid, S Sansom, MS Coarse-grained molecular dynamics simulations of membrane proteins and peptides. |
| title | Coarse-grained molecular dynamics simulations of membrane proteins and peptides. |
| title_full | Coarse-grained molecular dynamics simulations of membrane proteins and peptides. |
| title_fullStr | Coarse-grained molecular dynamics simulations of membrane proteins and peptides. |
| title_full_unstemmed | Coarse-grained molecular dynamics simulations of membrane proteins and peptides. |
| title_short | Coarse-grained molecular dynamics simulations of membrane proteins and peptides. |
| title_sort | coarse grained molecular dynamics simulations of membrane proteins and peptides |
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