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Article

Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors

1
Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Praca General Tiburcio 80, Rio de Janeiro 22290-270, Brazil
2
Federal Institute of Education, Science and Technology, Avenida Ministro Salgado Filho, 1000, Vila Velha 29106-010, Brazil
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Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003 Hradec Kralové, Czech Republic
4
Department of Neurology of the Medical Faculty of Charles University and University Hospital in Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic
5
INRS—Institut Armand-Frapier, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada
*
Authors to whom correspondence should be addressed.
Received: 8 November 2020 / Revised: 20 November 2020 / Accepted: 24 November 2020 / Published: 26 November 2020
(This article belongs to the Special Issue Biological Toxins: Challenges and Medical Countermeasures)
Ricin is a toxin found in the castor seeds and listed as a chemical weapon by the Chemical Weapons Convention (CWC) due to its high toxicity combined with the easiness of obtention and lack of available antidotes. The relatively frequent episodes of usage or attempting to use ricin in terrorist attacks reinforce the urge to develop an antidote for this toxin. In this sense, we selected in this work the current RTA (ricin catalytic subunit) inhibitor with the best experimental performance, as a reference molecule for virtual screening in the PubChem database. The selected molecules were then evaluated through docking studies, followed by drug-likeness investigation, molecular dynamics simulations and Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) calculations. In every step, the selection of molecules was mainly based on their ability to occupy both the active and secondary sites of RTA, which are located right next to each other, but are not simultaneously occupied by the current RTA inhibitors. Results show that the three PubChem compounds 18309602, 18498053, and 136023163 presented better overall results than the reference molecule itself, showing up as new hits for the RTA inhibition, and encouraging further experimental evaluation. View Full-Text
Keywords: ricin; ricin inhibitors; molecular dynamics; ligand-based virtual screening; chemical/biological warfare agents ricin; ricin inhibitors; molecular dynamics; ligand-based virtual screening; chemical/biological warfare agents
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MDPI and ACS Style

Botelho, F.D.; dos Santos, M.C.; Gonçalves, A.d.S.; Kuca, K.; Valis, M.; LaPlante, S.R.; França, T.C.C.; de Almeida, J.S.F.D. Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors. Toxins 2020, 12, 746. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120746

AMA Style

Botelho FD, dos Santos MC, Gonçalves AdS, Kuca K, Valis M, LaPlante SR, França TCC, de Almeida JSFD. Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors. Toxins. 2020; 12(12):746. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120746

Chicago/Turabian Style

Botelho, Fernanda D.; dos Santos, Marcelo C.; Gonçalves, Arlan d.S.; Kuca, Kamil; Valis, Martin; LaPlante, Steven R.; França, Tanos C.C.; de Almeida, Joyce S.F.D. 2020. "Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors" Toxins 12, no. 12: 746. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120746

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