The membrane spanning domain (MSD) of HIV-1 gp41 has been shown experimentally to anchor gp41 in the viral membrane and to play a role in fusion/infection. The mutation of the conserved midspan arginine to leucine (R694L) has normal surface expression, but diminished fusion activity. This mutant is further studied here using molecular dynamics (MD). The conformational distribution and PMF of the R694L MSD peptide were compared with that of the WT MSD peptide using the technique of metadynamics. The mutant and WT peptides both have stable, alpha-helical conformations but have different higher-energy structures. Equilibrium properties were also studied by long (300ns) MD. The presence of greater water around the C-terminal and the greater tilt of the WT MSD indicates that perhaps a role of the charged midspan arginine is partial solvation of the C-terminal, which may function to hold the viral membrane in a metastable prefusion state.

Effects of the midspan arginine-to-leucine mutation on the conformational distribution of the HIV-1 gp41 membrane spanning domain

244th National Meeting (2012)

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