Molecular dynamics simulation of HIV-1 fusion domain-membrane complexes: Insight into the N-terminal gp41 fusion mechanism.

To understand how viral proteins fuse with the cell membrane, a process that is important for the initial stages of infection, the conformation of the membrane-bound viral fusion peptides (FPs) must be identified. Here, molecular dynamics (MD) simulations were performed to investigate the conformation of the FP-16 and FP-23 of human immunodeficiency virus (HIV) bound to a dimyristoyl phosphatidylcholine (DMPC) bilayer. All FPs were found to penetrate into the bilayer despite the different initial orientations. In addition, the inclusion of residues 17 to 23 was found to play significant role in the fusion ability. Each of the FPs adopts at least two distinct conformations (predominantly α-helical and β-structures) while association with membrane. The peptide seriously affects structural and dynamical parameter of the contacted lipids. The previously experimental data together with our simulation data reveal that fusion ability depends on the membrane-associated conformation and alignment of the peptide.