Molecular Dynamics Simulations of Model Trans-Membrane Peptides in Lipid Bilayers: A Systematic Investigation of Hydrophobic Mismatch Export

@article{citeulike:550394, abstract = {Hydrophobic mismatch, which is the difference between the hydrophobic length of trans-membrane segments of a protein and the hydrophobic width of the surrounding lipid bilayer, is known to play a role in membrane protein function. We have performed molecular dynamics simulations of trans-membrane KALP peptides (sequence: GKK(LA)nLKKA) in phospholipid bilayers to investigate hydrophobic mismatch alleviation mechanisms. By varying systematically the length of the peptide (KALP15, KALP19, KALP23, KALP27, and KALP31) and the lipid hydrophobic length (DLPC, DMPC, and DPPC), a wide range of mismatch conditions were studied. Simulations of durations of 50-200 ns show that under positive mismatch, the system alleviates the mismatch predominantly by tilting the peptide and to a smaller extent by increased lipid ordering in the immediate vicinity of the peptide. Under negative mismatch, alleviation takes place by a combination of local bilayer bending and the snorkeling of the lysine residues of the peptide. Simulations performed at a higher peptide/lipid molar ratio (1:25) reveal slower dynamics of both the peptide and lipid relative to those at a lower peptide/lipid ratio (1:128). The lysine residues have favorable interactions with specific oxygen atoms of the phospholipid headgroups, indicating the preferred localization of these residues at the lipid/water interface.}, author = {Kandasamy, Senthil K. and Larson, Ronald G.}, citeulike-article-id = {550394}, citeulike-linkout-0 = {http://dx.doi.org/10.1529/biophysj.105.073395}, citeulike-linkout-1 = {http://www.biophysj.org/cgi/content/abstract/90/7/2326}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16428278}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16428278}, day = {1}, doi = {10.1529/biophysj.105.073395}, journal = {Biophys. J.}, keywords = {lipid, md, peptide, simulation}, month = {April}, number = {7}, pages = {2326--2343}, posted-at = {2006-03-14 05:56:18}, priority = {3}, title = {Molecular Dynamics Simulations of Model Trans-Membrane Peptides in Lipid Bilayers: A Systematic Investigation of Hydrophobic Mismatch}, url = {http://dx.doi.org/10.1529/biophysj.105.073395}, volume = {90}, year = {2006} }

TY - JOUR ID - citeulike:550394 L3 - citeulike-article-id:550394 N2 - Hydrophobic mismatch, which is the difference between the hydrophobic length of trans-membrane segments of a protein and the hydrophobic width of the surrounding lipid bilayer, is known to play a role in membrane protein function. We have performed molecular dynamics simulations of trans-membrane KALP peptides (sequence: GKK(LA)nLKKA) in phospholipid bilayers to investigate hydrophobic mismatch alleviation mechanisms. By varying systematically the length of the peptide (KALP15, KALP19, KALP23, KALP27, and KALP31) and the lipid hydrophobic length (DLPC, DMPC, and DPPC), a wide range of mismatch conditions were studied. Simulations of durations of 50-200 ns show that under positive mismatch, the system alleviates the mismatch predominantly by tilting the peptide and to a smaller extent by increased lipid ordering in the immediate vicinity of the peptide. Under negative mismatch, alleviation takes place by a combination of local bilayer bending and the snorkeling of the lysine residues of the peptide. Simulations performed at a higher peptide/lipid molar ratio (1:25) reveal slower dynamics of both the peptide and lipid relative to those at a lower peptide/lipid ratio (1:128). The lysine residues have favorable interactions with specific oxygen atoms of the phospholipid headgroups, indicating the preferred localization of these residues at the lipid/water interface. IS - 7 JF - Biophys. J. EP - 2343 TI - Molecular Dynamics Simulations of Model Trans-Membrane Peptides in Lipid Bilayers: A Systematic Investigation of Hydrophobic Mismatch VL - 90 SP - 2326 KW - lipid KW - md KW - peptide KW - simulation AU - Kandasamy, Senthil AU - Larson, Ronald PY - 2006/04/01/ UR - http://dx.doi.org/10.1529/biophysj.105.073395 ER -