Enrichment metrics for the identification of stabilizers of the telomeric G quartet using genetic algorithm
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Keywords

Enrichment metrics
Telomere
G quadruplex (G4
CompScore

How to Cite

Correa, M., & Solorzano, S. (2020). Enrichment metrics for the identification of stabilizers of the telomeric G quartet using genetic algorithm. Minerva, 1(1), 13-23. https://doi.org/10.47460/minerva.v1i1.2

Abstract

In this study, a combination of computer tools for coupling and virtual screening is detailed, in 108 active molecules and 3620 decoys to find stabilizers for G quadruplex (G4). To have more precise results, combinations of coupling programs with fifteen energy scoring functions were applied. The validation and evaluation of the metrics were done with the CompScore genetic algorithm. The results showed an increase in BEDROC and EF of 50% compared to other strategies, as well as reflecting early recognition of active molecules. From these results, it is possible to work with the molecules that showed a good early recognition and evaluate their effect as G4 stabilizers. This ensures more efficient and accurate results in the preclinical stage for the development of anticancer drugs.

Keywords: Enrichment metrics; telomere; G quadruplex (G4); CompScore.

 

https://doi.org/10.47460/minerva.v1i1.2
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References

M. Porru, P. Zizza, M. Franceschin, C. Leonetti y A. Biroccio. «EMICORON: A multi-targeting G4 ligand with

a promising preclinical profile» 2017. Biochimica et Biophysica Acta - General Subjects, 1861(5), 1362–1370. [En

línea]. Available: https://doi.org/10.1007/s00294-018-0836-6

K. Tomita. «How long does telomerase extend telomeres ? Regulation of telomerase release and telomere length homeostasis». Current Genetics, 64(6), 1177–1181. 2018. [En línea]. Available: https://doi.org/10.1016/j.bbagen. 2016.11.010

M. Jafri, S. Ansari, M. Alqahtani y J. Shay. «Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Medicine., 2016. [En línea]. Available: https://doi.org/10.3390/ijms19020482

J. Huppert y S. Balasubramanian. «G-quadruplexes in promoters throughout the human genome». 35(2), 406–

2007. [En línea]. Available: https://doi.org/10.1016/j.bbapap.2017.06.012

S. Joy, Vijayakumar, Y. M., & Sunhye, G. (2015). «Role of computer-aided drug design in modern drug discovery

». Archives of Pharmacal Research. 2015. [En línea]. Available: https://doi.org/10.1007/s12272-015-0640-5

S. Asamitsu, S. Obata, Z. Yu, T. Bando y H. Sugiyama. «Recent Progress of Targeted G-Quadruplex-Preferred

Ligands Toward Cancer Therapy». Molecules, 24(3), 429. 2019. [En línea]. Available: https://doi.org/10.3390/molecules24030429

R. Monsen y J. Trent. «Biochimie G-quadruplex virtual drug screening: A review». Biochimie, 152, 134–148.

[En línea]. Available: https://doi.org/10.1039/c9cc06748e

J. Beauvarlet, P. Bensadoun, E. Darbo, G. Labrunie, E. Richard, I. Draskovic, M. Djavaheri-mergny. «Modulation

of the ATM/autophagy pathway by G-quadruplex ligand tips the balance between senescence and apoptosis

in cancer cells». 1–18. 2019. [En línea]. Available: https://doi.org/10.1093/nar/gkz095

.Z. Crees, J. Girard, Z. Rios, G. Botting, K. Harrington y C. Shearrow. « Oligonucleotides and G-quadruplex

stabilizers: targeting telomeres and telomerase in cancer therapy».2014. [En línea]. Available: https://doi.org/10.2174/1381612820666140630100702

.M. Meier, A. Moya-Torres, N. Krahn, M. Mcdougall, L. Orriss, E. Mcrae, T. Patel. «Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge». (May), 1–13. 2018. [En línea].Available: https://doi.org/10.1093/nar/gky307

.M. Ivancich, Z. Schrank, L. Wojdyla, B. Leviskas y A. Kuckovic. «Treating Cancer by Targeting

Telomeres and Telomerase». 2017. [En línea]. Available: https://doi.org/10.3390/antiox6010015

.J. Maciejowski y T. Lange. De. «Telomeres in cancer: tumor». Nature Publishing Group. 2017. [En línea]. Available: https://doi.org/10.1038/nrm.2016.171

.M. Zurek, J. Altschmied, S. Kohlgrüber, N. Ale-agha y J. Haendeler. «Role of Telomerase in the Cardiovascular System». (CVD), 1–11. 2016. [En línea]. Available: https://doi.org/10.3390/genes7060029

.G. Zhou, X. Liu, Y. Li, S. Xu y C. Ma. «Telomere targeting with a novel G-quadruplex-interactive ligand BRACO-19 induces T-loop disassembly and telomerase displacement in human glioblastoma cells». 7(12). 2016. [En línea]. Available: https://doi.org/10.18632/oncotarget.7808

H. Berman. (2000). The Protein Data Bank. Nucleic Acids Research, 28(1), 235–242. [En línea]. Available: https://doi.org/10.1093/nar/28.1.235.

Cheminformatics Software, Molecular Modeling Software | OpenEye Scientific. Retrieved June 11, 2019, [En línea]. Available:https://www.eyesopen.com/.

OMEGA 3.1.1.2: OpenEye Scientific Software, Santa Fe, NM. [En línea]. Available: http://www.eyesopen.com

QUACPAC 2.0.1.2: OpenEye Scientific Software, Santa Fe, NM. [En línea]. Available: http://www.eyesopen.com

OEDOCKING 3.3.1.2: Software científico OpenEye, Santa Fe, NM. [En línea]. Available: http://www.eyesopen.com

Q. Li, J. Xiang, Q. Yang, H. Sun, A. Guan y Y. Tang. (2013). G4LDB: a database for discovering and studying G-quadruplex ligands. Nucleic Acids Research, 41(Database issue), D1115-23. [En línea]. Available: https://doi.org/10.1093/nar/gks1101

M. Mysinger, M. Carchia, J. Irwin y B. Shoichet. (2012). Directory of useful decoys, enhanced (DUD-E): Better ligands and decoys for better benchmarking. Journal of Medicinal Chemistry, 55(14), 6582–6594. [En línea]. Available:https://doi.org/10.1021/jm300687e

P. Lang, S. Brozell, S. Mukherjee, E. Pettersen, E. Meng, V. Thomas e I. Kuntz. (2009). DOCK 6: Combining techniques to model RNA – small molecule complexes. 1219–1230. [En línea]. Available: https://doi.org/10.1261/rna.1563609.HIV

J. Truchon y C.Bayly. (2007). Evaluating Virtual Screening Methods: Good and Bad Metrics for the “ Early Recognition ” Problem. 488–508. [En línea]. Available: https://doi.org/10.1021/ci600426e

D. Castillo-González, J. Mergny, A. De Rache, G. Pérez-Machado, M. Cabrera- Pérez, O. Nicolotti, M. Cruz-Monteagudo. (2015). Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands. Journal of Chemical Information and Modeling, 55(10), 2094–2110. https://doi.org/10.1021/acs.jcim.5b00415

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