vSDC: a method to improve early recognition in virtual screening when limited experimental resources are available

Journal of Cheminformatics
Ludovic ChaputLiliane Mouawad

Abstract

In drug design, one may be confronted to the problem of finding hits for targets for which no small inhibiting molecules are known and only low-throughput experiments are available (like ITC or NMR studies), two common difficulties encountered in a typical academic setting. Using a virtual screening strategy like docking can alleviate some of the problems and save a considerable amount of time by selecting only top-ranking molecules, but only if the method is very efficient, i.e. when a good proportion of actives are found in the 1-10 % best ranked molecules. The use of several programs (in our study, Gold, Surflex, FlexX and Glide were considered) shows a divergence of the results, which presents a difficulty in guiding the experiments. To overcome this divergence and increase the yield of the virtual screening, we created the standard deviation consensus (SDC) and variable SDC (vSDC) methods, consisting of the intersection of molecule sets from several virtual screening programs, based on the standard deviations of their ranking distributions. SDC allowed us to find hits for two new protein targets by testing only 9 and 11 small molecules from a chemical library of circa 15,000 compounds. Furthermore, vSDC, when applied to th...Continue Reading

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Citations

Jul 12, 2017·Journal of Chemical Information and Modeling·Connor W ColeyKlavs F Jensen
Sep 12, 2018·Chemical Society Reviews·Lukáš GrajciarPetr Nachtigall
Nov 1, 2017·Journal of Cheminformatics·Ludovic Chaput, Liliane Mouawad
Oct 28, 2019·Journal of Computational Chemistry·César R García-JacasFelix Martinez-Rios
Feb 8, 2020·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Janis RuskoVadims Bartkevics
May 14, 2020·Life·Harikrishna Reddy RallabandiYoung Jun Kim
Jan 30, 2019·Nature Communications·Laurel M LynchMatthew D Wallenstein
Oct 16, 2018·Frontiers in Pharmacology·Isabella A GuedesLaurent E Dardenne
Apr 17, 2019·Journal of Computer-aided Molecular Design·Mei Qian YauJason S E Loo
Sep 22, 2019·International Journal of Molecular Sciences·Pedro H M TorresFloriano P Silva-Jr
Jul 25, 2020·Journal of Biomolecular Structure & Dynamics·Ana Mércia Silva MascarenhasFranco Henrique Andrade Leite
Feb 6, 2020·Mini Reviews in Medicinal Chemistry·Mayara Dos Santos MaiaMarcus Tullius Scotti
Nov 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jinrong BaiXianli Meng
May 15, 2021·Journal of Biomolecular Structure & Dynamics·Prosper Obed ChukwuemekaFunmilayo Janet Adeojo
Aug 14, 2020·Journal of Chemical Information and Modeling·Natesh SinghBruno O Villoutreix
Jul 11, 2019·Journal of Chemical Information and Modeling·Sami T KurkinenPekka A Postila

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Methods Mentioned

BETA
Isothermal
NMR

Software Mentioned

SDC
Surflex
VS
vSDC sf
Maestro
protomol
GOLD
ChemPLP
R
DUD

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