Molecular simulations of membrane fusion structure of HIV GP41 n-terminal peptide

Abstract

To understand how the viral proteins destabilize the cell membrane in the initial stages of the fusion process, the conformation of membrane-bound viral fusion peptides must be elucidated. Here, molecular dynamics simulations were carried out to investigate structural and dynamical properties of the 16-residue, 23-residue and 30-residue fusion peptides (FPs) of human immunodeficiency virus bound to a dimyris-toyl phosphatidylcholine (DMPC) bilayer. The NMR data of the gp41 N-terminal FP in membrane-mimicking environments was used as the initial structures. The simulations revealed that the peptides adopt an α-helical structure during the entire simulations. In agreement with experimental studies, the helical content of more than 50% was observed for all FPs. However, the C-terminal part of the peptide is unstructured and rather more flexible than the N-terminal. The peptide forms stable complexes with the lipid bilayer by inserting its hydrophobic residues into the hydrophobic membrane core and exposing its polar terminal to water. Changes of the bilayer structure around the FP were also detected. Thus, it induces increasing of the thickness of bilayer and disordering of acyl chains of lipids in close proximity to the FP.