title: LiSiCA: A Software for Ligand-Based Virtual Screening and Its Application for the Discovery of Butyrylcholinesterase Inhibitors.
abstract: We developed LiSiCA (ligand similarity using clique algorithm)--ligand-based virtual screening software that uses a fast maximum clique algorithm to find two- and three-dimensional similarities between pairs of molecules and applied it to the discovery of novel potent butyrylcholinesterase inhibitors. LiSiCA, which runs in parallel on multiple processor cores, was successfully tested on the Database of Useful Decoys-Enhanced, to evaluate its ability to discriminate active molecules from decoys. We then applied LiSiCA for the discovery of novel inhibitors of human butyrylcholinesterase, a promising anti-Alzheimer target, using a known inhibitor as the reference compound. We demonstrated that LiSiCA is capable of finding potent nanomolar inhibitors, whose scaffolds differed from the reference compound, thus proving its ability for scaffold hopping and usefulness in drug discovery.
authors.affiliation: National Institute of Chemistry , Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
authors.forename: Samo
authors.initials: S
authors.lastname: Lešnik
authors.affiliation: Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska , Glagoljaška 8, SI-6000, Koper, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Štular
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, SI-1000, Ljubljana, Slovenia.
authors.forename: Boris
authors.initials: B
authors.lastname: Brus
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, SI-1000, Ljubljana, Slovenia.
authors.forename: Damijan
authors.initials: D
authors.lastname: Knez
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, SI-1000, Ljubljana, Slovenia.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.affiliation: Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska , Glagoljaška 8, SI-6000, Koper, Slovenia.
authors.forename: Dušanka
authors.initials: D
authors.lastname: Janežič
authors.affiliation: National Institute of Chemistry , Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Konc
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D012984:Software
chemical_list: D002800:Cholinesterase Inhibitors; D008024:Ligands; D002091:Butyrylcholinesterase