LiSiCA: A Software for Ligand-Based Virtual Screening and Its Application for the Discovery of Butyrylcholinesterase Inhibitors

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• 作者：Samo Le拧nik ; Tanja 艩tular ; Boris Brus ; Damijan Knez ; Stanislav Gobec ; Du拧anka Jane啪i膷 ; Janez Konc
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2015
• 出版时间：August 24, 2015
• 年：2015
• 卷：55
• 期：8
• 页码：1521-1528
• 全文大小：400K
• ISSN：1549-960X

文摘

We developed LiSiCA (ligand similarity using clique algorithm)鈥搇igand-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鈥擡nhanced, 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.