The Computational Core provides expertise at several stages of the overall Program workflow aimed at the generation of new and improved inhibitors of the HIV-1 Env machine. This expertise includes pharmacophore- based screening of external molecule databases to generate new lead molecules of interest, as well as consultation and simulation-based evaluation of new congeners derived from the extant set of authentic inhibitors already successfully generated by the Program. In each of these cases, we aim both to support the generation of new molecules with superior activity, especially in terms of breadth across HIV-1 strains, and to rationalize with 3D all-atom models the mechanisms by which our inhibitors interact with the HIV-1 envelope glycoprotein complex (Env) in its various conformational states. The Computational Core employs the latest and most reliable computational drug design software as well as custom algorithms for target preparation and conformational sampling based on all-atom molecular dynamics simulations.
