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 influenza virus hemagglutinin, was explored by Monte-Carlo technique starting with the fully buried in the membrane ideal alpha-helix. The lipid bilayer (of 30 Angstrom width) together with surrounding water were modeled by the atomic solvation parameters. During the simulation, residues 2-18 of the peptide retained alpha-helical conformation, and the peptide was found to be partially immersed into the bilayer. In the resulting low-energy conformers, the N-terminus was buried inside the membrane, its position with respect 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) were clustered in the space (Z(Nr), Theta) into 4 groups. To select low-energy states of the peptide compatible with NMR data, we calculated pK(a) values 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 pH units) were obtained for the group of states which is characterized by Theta = 15- 19 degrees and Z(Nr) = 3.5-4.5 Angstrom.