Optimizing high-throughput binding free energy simulations for small molecule drug discovery

Computational drug discovery methods are becoming increasingly prevalent in the drug discovery pipeline. Binding free energy (BFE) simulations are a class of molecular dynamics-based free energy methods that typically utilize a nonphysical "alchemical" thermodynamic pathway to compute protein-ligand complex binding free energies efficiently and rigorously. While the advent of GPU computing has greatly increased the speed of these simulations, the chemical spaces targeted for exploration are also rapidly expanding, demanding ever greater resources which can exceed a budget for a given campaign.