Artículo
Radusky, L.; Ruiz-Carmona, S.; Modenutti, C.; Barril, X.; Turjanski, A.G.; Martí, M.A. "LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening" (2017) Journal of Chemical Information and Modeling. 57(8):1741-1746
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Abstract:
Virtual screening is a powerful methodology to search for new small molecule inhibitors against a desired molecular target. Usually, it involves evaluating thousands of compounds (derived from large databases) in order to select a set of potential binders that will be tested in the wet-lab. The number of tested compounds is directly proportional to the cost, and thus, the best possible set of ligands is the one with the highest number of true binders, for the smallest possible compound set size. Therefore, methods that are able to trim down large universal data sets enriching them in potential binders are highly appreciated. Here we present LigQ, a free webserver that is able to (i) determine best structure and ligand binding pocket for a desired protein, (ii) find known binders, as well as potential ligands known to bind to similar protein domains, (iii) most importantly, select a small set of commercial compounds enriched in potential binders, and (iv) prepare them for virtual screening. LigQ was tested with several proteins, showing an impressive capacity to retrieve true ligands from large data sets, achieving enrichment factors of over 10%. LigQ is available at http://ligq.qb.fcen.uba.ar/. © 2017 American Chemical Society.
Registro:
| Documento: | Artículo |
| Título: | LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening |
| Autor: | Radusky, L.; Ruiz-Carmona, S.; Modenutti, C.; Barril, X.; Turjanski, A.G.; Martí, M.A. |
| Filiación: | Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, 1053, Argentina Insituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, Pabellón II, Buenos Aires, C1428EHA, Argentina Department of Physical Chemistry, Faculty of Pharmacy, Institute of Biomedicine (IBUB), University of Barcelona, Avgda. Diagonal 643, Barcelona, 08028, Spain Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, Barcelona, 08010, Spain |
| Palabras clave: | Binders; Bins; Proteins; Enrichment factors; Large database; Large datasets; Molecular targets; Potential ligand; Protein domains; Small molecule inhibitor; Virtual Screening; Ligands; ligand; protein; protein binding; binding site; chemistry; computer interface; drug database; Internet; metabolism; preclinical study; procedures; software; Binding Sites; Databases, Pharmaceutical; Drug Evaluation, Preclinical; Internet; Ligands; Protein Binding; Proteins; Software; User-Computer Interface |
| Año: | 2017 |
| Volumen: | 57 |
| Número: | 8 |
| Página de inicio: | 1741 |
| Página de fin: | 1746 |
| DOI: | http://dx.doi.org/10.1021/acs.jcim.7b00241 |
| Título revista: | Journal of Chemical Information and Modeling |
| Título revista abreviado: | J. Chem. Inf. Model. |
| ISSN: | 15499596 |
| CODEN: | JCISD |
| CAS: | protein, 67254-75-5; Ligands; Proteins |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15499596_v57_n8_p1741_Radusky |
Referencias:
- Shoichet, B.K., Virtual screening of chemical libraries (2004) Nature, 432, pp. 862-865
- McInnes, C., Virtual screening strategies in drug discovery (2007) Curr. Opin. Chem. Biol., 11, pp. 494-502
- Ruiz-Carmona, S., Alvarez-Garcia, D., Foloppe, N., Garmendia-Doval, A.B., Juhos, S., Schmidtke, P., Barril, X., Morley, S.D., RDock: A fast, versatile and open source program for docking ligands to proteins and nucleic acids (2014) PLoS Comput. Biol., 10, p. e1003571
- Barril, X., Hubbard, R.E., Morley, S.D., Virtual screening in structure-based drug discovery (2004) Mini-Rev. Med. Chem., 4, pp. 779-791
- Madhavi Sastry, G.M., Adzhigirey, M., Day, T., Annabhimoju, R., Sherman, W., Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments (2013) J. Comput.-Aided Mol. Des., 27, pp. 221-234
- Le Guilloux, V., Schmidtke, P., Tuffery, P., Fpocket: An open source platform for ligand pocket detection (2009) BMC Bioinf., 10, p. 168
- Volkamer, A., Kuhn, D., Rippmann, F., Rarey, M., DoGSiteScorer: A web server for automatic binding site prediction, analysis and druggability assessment (2012) Bioinformatics, 28, pp. 2074-2075
- O'Boyle, N.M., Banck, M., James, C.A., Morley, C., Vandermeersch, T., Hutchison, G.R., Open Babel: An open chemical toolbox (2011) J. Cheminf., 3, p. 33
- Csizmadia, F., JChem: Java applets and modules supporting chemical database handling from web browsers (2000) J. Chem. Inf. Comput. Sci., 40, pp. 323-324
- Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E., The protein data bank (2000) Nucleic Acids Res., 28, pp. 235-242
- The universal protein resource (UniProt) (2007) Nucleic Acids Res., 36, pp. D190-D195. , UniProt Consortium
- Webb, B., Sali, A., Comparative protein structure modeling using Modeller (2014) Curr. Protoc Bioinf.
- Schmidtke, P., Barril, X., Understanding and predicting druggability. A high-throughput method for detection of drug binding sites (2010) J. Med. Chem., 53 (15), pp. 5858-5867
- Bateman, A., Coin, L., Durbin, R., Finn, R.D., Hollich, V., Griffiths-Jones, S., Khanna, A., Eddy, S.R., The Pfam protein families database (2004) Nucleic Acids Res., 32, pp. D138-D141
- Gaulton, A., Bellis, L.J., Bento, A.P., Chambers, J., Davies, M., Hersey, A., Light, Y., Overington, J.P., ChEMBL: A large-scale bioactivity database for drug discovery (2012) Nucleic Acids Res., 40, pp. D1100-D1107
- Herraez, A., Biomolecules in the computer: Jmol to the rescue (2006) Biochem. Mol. Biol. Educ., 34, pp. 255-261
- Bajusz, D., Rácz, A., Héberger, K., Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations? (2015) J. Cheminf., 7, p. 1
- Irwin, J.J., Shoichet, B.K., ZINC-a free database of commercially available compounds for virtual screening (2005) J. Chem. Inf. Model., 45, pp. 177-182
- Jones, E., Oliphant, T., Peterson, P., SciPy: Open Source Scientific Tools for Python, , http://www.scipy.org, (version 0.17, 2016)
- Hunter, J.D., Matplotlib: A 2D graphics environment (2007) Comput. Sci. Eng., 9, pp. 90-95
- Radusky, L., Defelipe, L.A., Lanzarotti, E., Luque, J., Barril, X., Marti, M.A., Turjanski, A.G., TuberQ: A Mycobacterium tuberculosis protein druggability database (2014) Database, 2014, p. bau035
- Huang, N., Shoichet, B.K., Irwin, J.J., Benchmarking sets for molecular docking (2006) J. Med. Chem., 49, pp. 6789-6801
- Roy, A., Skolnick, J., LIGSIFT: An open-source tool for ligand structural alignment and virtual screening (2015) Bioinformatics, 31, pp. 539-544
- Von Behren, M.M., Bietz, S., Nittinger, E., Rarey, M., MRAISE: An alternative algorithmic approach to ligand-based virtual screening (2016) J. Comput.-Aided Mol. Des., 30, pp. 583-594
- Kirchmair, J., Distinto, S., Markt, P., Schuster, D., Spitzer, G.M., Liedl, K.R., Wolber, G., How to optimize shape-based virtual screening: Choosing the right query and including chemical information (2009) J. Chem. Inf. Model., 49, pp. 678-692
- Halgren, T., Identifying and Characterizing Binding Sites and Assessing Druggability (2009) J. Chem. Inf. Model., 49 (2), pp. 377-389
- Radusky, L.G., Hassan, S.S., Lanzarotti, E., Tiwari, S., Jamal, S.B., Ali, J., Ali, A., Azevedo, V.A.C., An integrated structural proteomics approach along the druggable genome of Corynebacterium pseudotuberculosis species for putative druggable targets (2015) BMC Genomics, 16 (5), p. S9
Citas:
---------- APA ----------
Radusky, L., Ruiz-Carmona, S., Modenutti, C., Barril, X., Turjanski, A.G. & Martí, M.A. (2017) . LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening. Journal of Chemical Information and Modeling, 57(8), 1741-1746.http://dx.doi.org/10.1021/acs.jcim.7b00241
---------- CHICAGO ----------
Radusky, L., Ruiz-Carmona, S., Modenutti, C., Barril, X., Turjanski, A.G., Martí, M.A. "LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening" . Journal of Chemical Information and Modeling 57, no. 8 (2017) : 1741-1746.http://dx.doi.org/10.1021/acs.jcim.7b00241
---------- MLA ----------
Radusky, L., Ruiz-Carmona, S., Modenutti, C., Barril, X., Turjanski, A.G., Martí, M.A. "LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening" . Journal of Chemical Information and Modeling, vol. 57, no. 8, 2017, pp. 1741-1746.http://dx.doi.org/10.1021/acs.jcim.7b00241
---------- VANCOUVER ----------
Radusky, L., Ruiz-Carmona, S., Modenutti, C., Barril, X., Turjanski, A.G., Martí, M.A. LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening. J. Chem. Inf. Model. 2017;57(8):1741-1746.http://dx.doi.org/10.1021/acs.jcim.7b00241
