This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.105.073395v1 90/7/2326    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kandasamy, S. K. Articles by Larson, R. G. Search for Related Content PubMed PubMed Citation Articles by Kandasamy, S. K. Articles by Larson, R. G.

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

Chemical Engineering Department, University of Michigan, Ann Arbor, Michigan

Correspondence: Address reprint requests to R. G. Larson, Tel.: 734-936-0772; E-mail: rlarson{at}umich.edu.

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.

This article has been cited by other articles:

				U. Zimmerli and P. Koumoutsakos Simulations of Electrophoretic RNA Transport Through Transmembrane Carbon Nanotubes Biophys. J., April 1, 2008; 94(7): 2546 - 2557. [Abstract] [Full Text] [PDF]

				A. E. Daily, D. V. Greathouse, P. C. A. van der Wel, and R. E. Koeppe 2nd Helical Distortion in Tryptophan- and Lysine-Anchored Membrane-Spanning {alpha}-Helices as a Function of Hydrophobic Mismatch: A Solid-State Deuterium NMR Investigation Using the Geometric Analysis of Labeled Alanines Method Biophys. J., January 15, 2008; 94(2): 480 - 491. [Abstract] [Full Text] [PDF]

				S. Esteban-Martin and J. Salgado The Dynamic Orientation of Membrane-Bound Peptides: Bridging Simulations and Experiments Biophys. J., December 15, 2007; 93(12): 4278 - 4288. [Abstract] [Full Text] [PDF]

				W. L. Vos, M. Schor, P. V. Nazarov, R. B. M. Koehorst, R. B. Spruijt, and M. A. Hemminga Structure of Membrane-Embedded M13 Major Coat Protein Is Insensitive to Hydrophobic Stress Biophys. J., November 15, 2007; 93(10): 3541 - 3547. [Abstract] [Full Text] [PDF]

				G. Brannigan and F. L. H. Brown Contributions of Gaussian Curvature and Nonconstant Lipid Volume to Protein Deformation of Lipid Bilayers Biophys. J., February 1, 2007; 92(3): 864 - 876. [Abstract] [Full Text] [PDF]