Molecular Dynamics Simulations Of Model Trans Membrane Peptides In Lipid Bilayers A Systematic Investigation Of Hydrophobic Mismatch Biophysj 105.073395v1英文电子书.pdfVIP

Biophys J BioFAST, published on January 20, 2006 as doi:10.1529/biophysj.105.073395 This un-edited manuscript has been accepted for publication in Biophysical Journal and is freely available on BioFast at . The final copyedited version of the paper may be found at . Molecular Dynamics Simulations of Model Trans-membrane Peptides in Lipid Bilayers: A Systematic Investigation of Hydrophobic Mismatch Senthil K. Kandasamy and Ronald G. Larson* Chemical Engineering Department, The University of Michigan. Ann Arbor, MI. 48109 senthilk@ rlarson@ 1 Copyright 2006 by The Biophysical Society. 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) LKKA) in phospholipid n 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 50 ns - 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 r