Fast and accurate predictions of binding free energies using MM‐PBSA and MM‐GBSA

In the drug discovery process, accurate methods of computing the affinity of small molecules with a biological target are strongly needed. This is particularly true for molecular docking and virtual screening methods, which use approximated scoring functions and struggle in estimating binding energies in correlation with experimental values. Among the various methods, MM-PBSA and MM-GBSA are emerging as useful and effective approaches. Although these methods are typically applied to large collections of equilibrated structures of protein-ligand complexes sampled during molecular dynamics in water, the possibility to reliably estimate ligand affinity using a single energy-minimized structure and implicit…