A Free Web-Based Protocol to Assist Structure-Based Virtual Screening Experiments
Abstract
:1. Introduction
2. Results and Discussion
2.1. A Free Web-Based Protocol Dedicated to Small-Molecule Virtual Screening
2.1.1. Chemical Compound Preparation
2.1.2. Docking-Based Virtual Screening
2.1.3. Molecular Mechanics Refinement
2.2. Screening of Approved Drugs Using the Web-Based Protocol for Drug Repositioning
2.2.1. Fluspirilene
2.2.2. Raloxifene
2.2.3. Thalidomide
3. Materials and Methods
3.1. Web Servers
3.1.1. FAF-Drugs4 Web Server
3.1.2. MTiOpenScreen Web Server
3.1.3. AMMOS2 Web Server
3.2. Preparation of Data for Performance Assessment
3.2.1. Compound Collection Preparation
3.2.2. Protein Structure Preparation and Calculation Parameters
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
RPBS | Ressource Parisienne en Bioinformatique Structurale |
AMMOS2 | Automatic Molecular Mechanics Optimization for in silico Screening |
PAINS | pan-assay interference compounds |
CDK2 | cyclin-dependent kinase 2 |
ER | estrogen receptor |
FDA | food drug administration |
IL-6 | interleukin-6 |
MW | molecular weight |
PDB | Protein Data Bank |
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Drug, PDB ID | AutoDock Vina | AMMOS2 Case 1 | AMMOS2 Case 3 | AMMOS2 Case 4 | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
score | rank | Energy before min | Energy after min | rank | Energy before min | Energy after min | rank | Energy before min | Energy after min | rank | |
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
Fluspirilene 1PXI | −8.7 | 805 | 207.75 | 3.98 | 520 | 195.32 | 8.96 | 665 | >1000.0 | 15.97 | 654 |
Fluspirilene 1VYZ | −9.2 | 443 | 111.96 | −29.37 | 342 | 657.01 | −13.31 | 683 | >1000.0 | −8.51 | 619 |
Raloxifene 3L5H | −7.5 | 126 | >1000.0 | −72.11 | 480 | >1000.0 | −59.01 | 609 | >1000.0 | −25.50 | 850 |
Raloxifene 1P9M | −6.5 | 737 | −49.74 | −124.65 | 292 | −49.73 | −119.48 | 455 | −49.74 | −114.09 | 466 |
Thalidomide 4CI1 | −9.8 | 196 | −38.11 | −40.31 | 341 | −16.34 | −41.49 | 578 | −38.11 | −40.31 | 555 |
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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. https://doi.org/10.3390/ijms20184648
Lagarde N, Goldwaser E, Pencheva T, Jereva D, Pajeva I, Rey J, Tuffery P, Villoutreix BO, Miteva MA. A Free Web-Based Protocol to Assist Structure-Based Virtual Screening Experiments. International Journal of Molecular Sciences. 2019; 20(18):4648. https://doi.org/10.3390/ijms20184648
Chicago/Turabian StyleLagarde, Nathalie, Elodie Goldwaser, Tania Pencheva, Dessislava Jereva, Ilza Pajeva, Julien Rey, Pierre Tuffery, Bruno O. Villoutreix, and Maria A. Miteva. 2019. "A Free Web-Based Protocol to Assist Structure-Based Virtual Screening Experiments" International Journal of Molecular Sciences 20, no. 18: 4648. https://doi.org/10.3390/ijms20184648