Evaluating the predictivity of virtual screening for ABL kinase inhibitors to hinder drug resistance.
Bottom Line: However, any practical ligand set (of active or inactive compounds) chosen for deriving new virtual screening approaches cannot fully represent all relevant chemical space for potential new compounds.We show how various scoring functions and choice of inactive ligand sets influence overall and early enrichment of the libraries.We believe that this study can be extended to other therapeutically important kinases in prospective virtual screening studies.
Affiliation: The Norwegian Structural Biology Center, Department of Chemistry, University of Tromsø, 9037, Tromsø, Norway.Show MeSH
Related in: MedlinePlus
Mentions: Despite some overlap, active inhibitors and DUD decoys map to distinguishable volumes in chemical space (Figure6A). This itself provides information to filter sets of potential inhibitors to eliminate compounds that match decoys rather than inhibitors. In contrast, plotting ABL1-wt selective inhibitors versus dual active ABL1 inhibitors does not distinguish the sets (Figure6B) in the major PC dimensions.
Affiliation: The Norwegian Structural Biology Center, Department of Chemistry, University of Tromsø, 9037, Tromsø, Norway.