Investigation on the sucrose binding pocket of HIV-1 Integrase by molecular dynamics and synergy experiments

Enzymes whose catalytic activity depends on multimeric assembly are targets for inhibitors that perturb the interactions between the protein subunits such as the HIV-1 Integrase (IN). Sucrose has been recently crystallized in complex with IN revealing an allosteric binding pocket at the monomer-monomer interface. Herein, molecular dynamics were applied to theoretically test the effect of this small ligand on IN. As a result, such a compound increases the mutual free energy of binding between the two interacting monomers. Biological experiments confirmed the computational forecast.