title: Exploring different virtual screening strategies for acetylcholinesterase inhibitors.
abstract: The virtual screening problems associated with acetylcholinesterase (AChE) inhibitors were explored using multiple shape, and structure-based modeling strategies. The employed strategies include molecular docking, similarity search, and pharmacophore modeling. A subset from directory of useful decoys (DUD) related to AChE inhibitors was considered, which consists of 105 known inhibitors and 3732 decoys. Statistical quality of the models was evaluated by enrichment factor (EF) metrics and receiver operating curve (ROC) analysis. The results revealed that electrostatic similarity search protocol using EON (ET_combo) outperformed all other protocols with outstanding enrichment of >95% in top 1% and 2% of the dataset with an AUC of 0.958. Satisfactory performance was also observed for shape-based similarity search protocol using ROCS and PHASE. In contrast, the molecular docking protocol performed poorly with enrichment factors <30% in all cases. The shape- and electrostatic-based similarity search protocol emerged as a plausible solution for virtual screening of AChE inhibitors.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, India.
authors.forename: Nibha
authors.initials: N
authors.lastname: Mishra
authors.forename: Arijit
authors.initials: A
authors.lastname: Basu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000378:metabolism; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000032:analysis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry; D012372:ROC Curve; D014584:User-Computer Interface
chemical_list: D002800:Cholinesterase Inhibitors; D008024:Ligands; D050505:Mutant Proteins; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase