Drug discovery is being pursued through computer-aided design. For de novo lead generation, the BOMB program can build large combinatorial libraries in a protein binding site using a selected core and substituents, and the informatics program QikProp is applied to filter all designed molecules to ensure that they have drug-like properties. Monte Carlo/free-energy perturbation simulations are then executed to refine the binding predictions for the best scoring leads including ca. 2000 explicit water molecules and extensive sampling for the protein and ligand. FEP calculations for optimization of substituents on an aromatic ring and for choice of heterocycles are common. Successful application is illustrated for several protein targets including HIV-1, JAK2 kinase, and the main protease of SARS-CoV-2. Micromolar leads have been rapidly advanced to extraordinarily potent inhibitors.

Simulation and informatics for drug design

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.