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.

Structural analysis of lead fullerene-based inhibitor bound to human immunodeficiency virus type 1 protease in solution from molecular dynamics simulations.

Molecular dynamics (MD) simulations of the HIV-1 protease (HIVP) complexed with lead fullerene-based inhibitor (diphenyl C60 alcohol) in the three protonated states, unprotonated (Un-), monoprotonated (Mono-), and diprotonated (Di-) states at Asp25 and Asp25' were performed. As the X-ray structure of the investigated complex is not available, it was built up starting with the X-ray crystallographic structure of the HIVP complexed with non-peptide inhibitor (PDB code: 1AID) and that of the diphenyl C60 alcohol optimized using the integrated ONIOM molecular orbital calculations. The inhibitor was, then, introduced into the enzyme pocket using a molecular docking method.