Journal
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Volume 58, Issue 6, Pages 1205-1213Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jcim.8b00036
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Funding
- research project Bioinformatica Estrutural de Proteinas: Modelos, Algoritmos e Aplicacoes Biotecnologicas [51/2013, AUXPE1375/2014/CAPES]
- Brazilian National Council for Scientific and Technological Development (CNPq) [305271/2013-0]
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Ricin is a ribosome-inactivating protein (RIP type 2) consisting of two subunits, ricin toxin A (RTA) and ricin toxin B (RTB). Because of its cytotoxicity, ricin has worried world authorities for its potential use as a chemical weapon; therefore, its inhibition is of great biotechnological interest. RTA is the target for inhibitor synthesis, and pterin derivatives are promising candidates to inhibit it. In this study, we used a combination of the molecular docking approach and fast steered molecular dynamics (SMD) to assess the correlation between non equilibrium work, < W >, and the IC50 for six RTA inhibitors. The results showed that molecular docking is a powerful tool to predict good bioactive poses of RTA inhibitors, and < W > presented a strong correlation with IC50 (R-2 = 0.961). Such a profile ranked the RTA inhibitors better than the molecular docking approach. Therefore, the combination of docking and fast SMD simulation was shown to be a promising tool to distinguish RTA-active inhibitors from inactive ones and could be used as postdocking filtering approach.
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