Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations.

ABSTRACT: HIV-1 protease is an essential enzyme in the life cycle of the HIV-1 virus. The conformational dynamics of the flap region of the protease is critical for the ligand binding mechanism, as well as for the catalytic activity. The monoclonal antibody F11.2.32 raised against HIV-1 protease inhibits its activity on binding. We have studied the conformational dynamics of protease in its free, inhibitor ritonavir and antibody bound forms using molecular dynamics simulations. We find that upon Ab binding to the epitope region (residues 36-46) of protease, the overall flexibility of the protease is decreased including the flap region and the active site, which is similar to the decrease in flexibility observed by inhibitor binding to the protease. This suggests an allosteric mechanism to inhibit pr

SUBMITTER: Badaya A 

PROVIDER: S-EPMC7098958 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature