Molecular Dynamics Simulations of Folding and Insertion of the Ebola Vrus Fusion Peptide into a Membrane Bilayer

This paper presents replica-exchange molecular dynamics simulations of the folding and insertion of a 16residue Ebola virus fusion peptide into a membrane bilayer. We applied a multi-resolution computational approach of modeling the peptide at the all-atom level and the membrane-aqueous bilayer by a generalized Born continuum approximation. We found that interfacial folding of the peptide is not required for membrane insertion and that regardless of the starting conformation (either folded or unfolded) the simulations of 20 ns converged to yield a conformational preference of forming an (i,i+4) backbone α-helical structure with the central residues embedded approximately 4-6 Å below the surface of the membrane and the two terminal charged residues exposed to the solvent layer. The conformational population distributions of the peptide and a possible folding/insertion pathway are discussed in terms of energy landscape theory.