Solvent-Site Prediction for Fragment Docking and Its Implication on Fragment-Based Drug Discovery.

ABSTRACT: The accuracy in the posing and scoring of low-affinity fragments is still a main challenge in fragment-based virtual screenings. The positive impact of including structural or predicted water molecules during docking on the docking performance is discussed frequently and is not conclusive so far. We present a comprehensive statistical evaluation of the effect of including crystallographic or predicted water molecules on the docking performance of fragment redocking. Further, cross-docking fragments into binding sites occupied by larger ligands and vice versa were elucidated. These cross-dockings imitate realistic use cases of fragment hit identification and fragment growing or synthon-based virtual screenings, respectively. Therefore, a new benchmark data set, called Frag2Lead conta

SUBMITTER: Almena Rodriguez L 

PROVIDER: S-EPMC12690578 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature