Determining the Relative Binding Affinity of Ricin Toxin A Inhibitors by Using Molecular Docking and Nonequilibrium Work

Journal of Chemical Information and Modeling
Elton J F ChavesGerd B Rocha

Abstract

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 nonequilibrium 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 ( R2 = 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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Citations

Feb 3, 2021·Journal of Biomolecular Structure & Dynamics·Elton José Ferreira ChavesGerd Bruno Rocha
Feb 14, 2020·Journal of Chemical Information and Modeling·Maciej Majewski, Xavier Barril
Jan 7, 2022·Journal of Agricultural and Food Chemistry·Abraham Vidal-LimonAndrea M Liceaga

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