title: Water-membrane partition thermodynamics of an amphiphilic lipopeptide: an enthalpy-driven hydrophobic effect.
abstract: To shed light on the driving force for the hydrophobic effect that partitions amphiphilic lipoproteins between water and membrane, we carried out an atomically detailed thermodynamic analysis of a triply lipid modified H-ras heptapeptide anchor (ANCH) in water and in a DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) bilayer. Combining molecular mechanical and continuum solvent approaches with an improved technique for solute entropy calculation, we obtained an overall transfer free energy of approximately -13 kcal mol(-1). This value is in qualitative agreement with free energy changes derived from a potential of mean force calculation and indirect experimental observations. Changes in free energies of solvation and ANCH conformational reorganization are unfavorable, whereas ANCH-DMPC interactions-especially van der Waals-favor insertion. These results are consistent with an enthalpy-driven hydrophobic effect, in accord with earlier calorimetric data on the membrane partition of other amphiphiles. Furthermore, structural and entropic analysis of molecular dynamics-generated ensembles suggests that conformational selection may play a hitherto unappreciated role in membrane insertion of lipid-modified peptides and proteins.
authors.affiliation: Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California 92093-0365, USA. abebe@mccammon.ucsd.edu
authors.forename: Alemayehu A
authors.initials: AA
authors.lastname: Gorfe
authors.forename: Riccardo
authors.initials: R
authors.lastname: Baron
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008074:Lipoproteins; D009842:Oligopeptides; D012997:Solvents; D014867:Water; D004134:Dimyristoylphosphatidylcholine