Lead Finder docking and virtual screening evaluation with Astex and DUD test sets.

Journal of Computer-aided Molecular Design
Fedor N NovikovGhermes G Chilov

Abstract

Lead Finder is a molecular docking software. Sampling uses an original implementation of the genetic algorithm that involves a number of additional optimization procedures. Lead Finder's scoring functions employ a set of semi-empiric molecular mechanics functionals that have been parameterized independently for docking, binding energy predictions and rank-ordering for virtual screening. Sampling and scoring both utilize a staged approach, moving from fast but less accurate algorithm versions to computationally more intensive but more accurate versions. Lead Finder includes tools for the preparation of full atom protein and ligand models. In this exercise, Lead Finder achieved 72.9% docking success rate on the Astex test set when the original author-prepared full atom models were used, and 74.1% success rate when the structures were prepared by Lead Finder. The major cause of docking failures were scoring errors resulting from the use of imperfect solvation models. In many cases, docking errors could be corrected by the proper protonation and the use of correct cyclic conformations of ligands. In virtual screening experiments on the DUD test set the early enrichment factor of several tens was achieved on average. However, the ar...Continue Reading

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Citations

Jul 7, 2012·Journal of Chemical Information and Modeling·Álvaro Cortés CabreraAntonio Morreale
Jul 6, 2014·Journal of Computer-aided Molecular Design·Angela M HenzlerMatthias Rarey
Jun 22, 2012·Journal of Medicinal Chemistry·Michael M MysingerBrian K Shoichet
Jul 8, 2015·Journal of Chemical Information and Modeling·Brian P KelleySteven W Muchmore
Feb 20, 2013·Journal of Computational Chemistry·Marcel Schumann, Roger S Armen
Mar 27, 2015·Journal of Molecular Recognition : JMR·Elizabeth YurievPaul A Ramsland
May 6, 2015·Journal of Computer-aided Molecular Design·Ann E Cleves, Ajay N Jain
Jun 18, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Giulio PoliTiziano Tuccinardi
Jun 30, 2016·Journal of Medicinal Chemistry·Marcel L VerdonkPrakash Chandra Rathi
Sep 6, 2018·Current Medicinal Chemistry·Vladimir B SulimovAlexey V Sulimov
Nov 13, 2015·Journal of Computational Chemistry·Vincent ZoeteOlivier Michielin
Apr 23, 2014·Journal of Chemical Information and Modeling·Jie XiaXiang Simon Wang
Apr 30, 2014·Journal of Chemical Information and Modeling·Paul C D HawkinsGregory L Warren
Jun 16, 2015·Journal of Chemical Information and Modeling·Francis Gaudreault, Rafael J Najmanovich
Dec 16, 2020·Journal of Chemical Information and Modeling·Horacio Pérez-SánchezJosé Manuel Villalgordo

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