Effect of flanking residues on the conformational sampling of the internal fusion peptide from Ebola virus

Abstract

Fusion peptides mediate viral and host-cell membrane fusion during viral entry. The monomeric form of the internal fusion peptide from Ebola virus was studied in membrane bilayer and water environments with computer simulations using replica exchange sampling and an implicit solvent description of the environment. Wild-type Ebola fusion peptide (EFP), the W8A mutant form, and an extended construct with flanking residues were examined. It was found that the monomeric form of wild-type EFP adopts coil-helix-coil structure with a short helix from residues 8 to 11 mostly sampling orientations parallel to the membrane surface. W8A mutation disrupts the helicity in the N-terminal region of the peptide and leads to a preference for slightly oblique orientation relative to the membrane surface. The addition of flanking residues also alters the fusion peptide conformation with either a helix-break-helix structure or extended N and C-termini and reduced membrane insertion. In water, the fusion peptide is found to adopt structures with low helicity.