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Open AccessArticle

A Free Web-Based Protocol to Assist Structure-Based Virtual Screening Experiments

1
Laboratoire GBCM, EA7528, Conservatoire National des Arts et Métiers, 2 Rue Conté, Hésam Université, 75003 Paris, France
2
Inserm U1268 MCTR, CNRS UMR 8038 CiTCoM - Univ. de Paris, Faculté de Pharmacie de Paris, 4 av de l’Observatoire, CEDEX 06, 75270 Paris, France
3
Department of QSAR and Molecular Modelling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 105 Acad G. Bonchev Str., 1113 Sofia, Bulgaria
4
Université de Paris, BFA, UMR 8251, CNRS, ERL U1133, Inserm, RPBS, F-75013 Paris, France
5
University of Lille, Inserm, Institut Pasteur de Lille, U1177, F-59000 Lille, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(18), 4648; https://doi.org/10.3390/ijms20184648
Received: 16 July 2019 / Revised: 3 September 2019 / Accepted: 17 September 2019 / Published: 19 September 2019
(This article belongs to the Special Issue Recent Advances in Virtual Screening)
Chemical biology and drug discovery are complex and costly processes. In silico screening approaches play a key role in the identification and optimization of original bioactive molecules and increase the performance of modern chemical biology and drug discovery endeavors. Here, we describe a free web-based protocol dedicated to small-molecule virtual screening that includes three major steps: ADME-Tox filtering (via the web service FAF-Drugs4), docking-based virtual screening (via the web service MTiOpenScreen), and molecular mechanics optimization (via the web service AMMOS2 [Automatic Molecular Mechanics Optimization for in silico Screening]). The online tools FAF-Drugs4, MTiOpenScreen, and AMMOS2 are implemented in the freely accessible RPBS (Ressource Parisienne en Bioinformatique Structurale) platform. The proposed protocol allows users to screen thousands of small molecules and to download the top 1500 docked molecules that can be further processed online. Users can then decide to purchase a small list of compounds for in vitro validation. To demonstrate the potential of this online-based protocol, we performed virtual screening experiments of 4574 approved drugs against three cancer targets. The results were analyzed in the light of published drugs that have already been repositioned on these targets. We show that our protocol is able to identify active drugs within the top-ranked compounds. The web-based protocol is user-friendly and can successfully guide the identification of new promising molecules for chemical biology and drug discovery purposes. View Full-Text
Keywords: web server; virtual screening; docking; molecular mechanics; structure refinement; ADME-Tox web server; virtual screening; docking; molecular mechanics; structure refinement; ADME-Tox
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MDPI and ACS Style

Lagarde, N.; Goldwaser, E.; Pencheva, T.; Jereva, D.; Pajeva, I.; Rey, J.; Tuffery, P.; Villoutreix, B.O.; Miteva, M.A. A Free Web-Based Protocol to Assist Structure-Based Virtual Screening Experiments. Int. J. Mol. Sci. 2019, 20, 4648.

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