Fusion peptide interaction with lipid bilayer: Modeling with Monte Carlo simulation and continuum electrostatics calculation

Conformation of 20-residue peptide E5, an analog of the fusion peptide of i nfluenza virus hemagglutinin, was explored by Monte-Carlo technique startin g with the fully buried in the membrane ideal alpha-helix. The lipid bilaye r (of 30 Angstrom width) together with surrounding water were modeled by th e atomic solvation parameters. During the simulation, residues 2-18 of the peptide retained alpha-helical conformation, and the peptide was found to b e partially immersed into the bilayer. In the resulting low-energy conforme rs, the N-terminus was buried inside the membrane, its position with respec t to the bilayer surface (Z(Nr)) being varied from 2.5 to 7.5 Angstrom, and the orientation of the helical axis relative to the membrane plane (Theta) - from 10 to 35 degrees. The low-energy conformers (below -200 kcal/mol) we re clustered in the space (Z(Nr), Theta) into 4 groups. To select low-energ y states of the peptide compatible with NMR data, we calculated pK(a) value s of E5 ionizable groups and compared them with the experimental values. It was shown that the best correlation coefficient (0.87) and rmsd (0.68 in p H units) were obtained for the group of states which is characterized by Th eta = 15- 19 degrees and Z(Nr) = 3.5-4.5 Angstrom.