Coarse-grained molecular dynamics simulations of membrane proteins and peptides.

@article{citeulike:965543, abstract = {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 (>100ns) 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 200ns CG-MD simulation of LacY in a DPPC bilayer with a 50ns 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.}, address = {Department of Biochemistry, University of Oxford, South Parks Road Oxford, OX1 3QU, UK.}, author = {Bond, Peter J J. and Holyoake, John and Ivetac, Anthony and Khalid, Syma and Sansom, Mark S P S. }, citeulike-article-id = {965543}, doi = {http://dx.doi.org/10.1016/j.jsb.2006.10.004}, issn = {1047-8477}, journal = {J Struct Biol}, keywords = {coarse-grain, lipid, membrane, protein}, month = {October}, posted-at = {2006-11-28 20:20:31}, priority = {2}, title = {Coarse-grained molecular dynamics simulations of membrane proteins and peptides.}, url = {http://dx.doi.org/10.1016/j.jsb.2006.10.004}, year = {2006} }

TY - JOUR ID - citeulike:965543 L3 - citeulike-article-id:965543 N2 - 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 (>100ns) 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 200ns CG-MD simulation of LacY in a DPPC bilayer with a 50ns 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. JF - J Struct Biol SN - 1047-8477 AD - Department of Biochemistry, University of Oxford, South Parks Road Oxford, OX1 3QU, UK. TI - Coarse-grained molecular dynamics simulations of membrane proteins and peptides. KW - coarse-grain KW - lipid KW - membrane KW - protein AU - Bond, Peter J AU - Holyoake, John AU - Ivetac, Anthony AU - Khalid, Syma AU - Sansom, Mark S P PY - 2006/10/20/ UR - http://dx.doi.org/10.1016/j.jsb.2006.10.004 ER -