Factors important for fusogenic activity of peptides: molecular modeling study of analogs of fusion peptide of influenza virus hemagglutinin

Nine analogs of fusion peptide of influenza virus hemagglutinin whose membr ane perturbation activity has been thoroughly tested [Murata et al, (1992) Biochemistry 31, 1986-1992; Murata ct al, (1993) Biophys, J, 64, 724-734] w ere characterized by molecular modeling techniques with the aim of delineat ing any specific structural and/or hydrophobic properties inherent in pepti des with fusogenic activity. It was shown that, regardless of characteristi cs common to all analogs (peripheral disposition at the water-lipid interfa ce, amphiphilic nature, alpha-helical structure, etc.), only fusion active peptides reveal a specific 'tilted oblique-oriented' pattern of hydrophobic ity on their surfaces and a certain depth of penetration to the non-polar m embrane core. The conclusion was reached that these factors are among the m ost important for the specific destabilization of a bilayer, which is follo wed by membrane fusion, (C) 1999 Federation of European Biochemical Societi es.