A combined molecular dynamics simulation and DFT study on mercapto-benzamide inhibitors for the HIV NCp7 protein

Molecular dynamics and quantum simulations are performed to elucidate some aspects of the action mechanism of mercapto-benzamides, a proposed class of antivirals against HIV-1. These molecules act as prodrugs that, after modifications in the biological environment, are able to denature the HIV nucleocapsid protein 7, a metal binder protein, with two zinc finger motifs, vital for RNA maturation and viral replication. Despite their attractive features, these molecules and their biological target are not well understood. Simulations were performed to support a proposed action mechanism, based on the activation of mercapto-benzamides by acetylation, targeting a relatively rare protein hydrolyzed state, followed by