da Mota VHS, Freire de Melo F, de Brito BB, Silva FAFD, Teixeira KN. Molecular docking of DS-3032B, a mouse double minute 2 enzyme antagonist with potential for oncology treatment development. World J Clin Oncol 2022; 13(6): 496-504 [PMID: 35949428 DOI: 10.5306/wjco.v13.i6.496]
Corresponding Author of This Article
Kádima Nayara Teixeira, PhD, Adjunct Professor, Campus Toledo, Universidade Federal do Paraná, Road 182, km 320/321, Toledo 85.919-899, Paraná, Brazil. kadimateixeira@ufpr.br
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
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da Mota VHS, Freire de Melo F, de Brito BB, Silva FAFD, Teixeira KN. Molecular docking of DS-3032B, a mouse double minute 2 enzyme antagonist with potential for oncology treatment development. World J Clin Oncol 2022; 13(6): 496-504 [PMID: 35949428 DOI: 10.5306/wjco.v13.i6.496]
World J Clin Oncol. Jun 24, 2022; 13(6): 496-504 Published online Jun 24, 2022. doi: 10.5306/wjco.v13.i6.496
Molecular docking of DS-3032B, a mouse double minute 2 enzyme antagonist with potential for oncology treatment development
Vítor Hugo Sales da Mota, Fabrício Freire de Melo, Breno Bittencourt de Brito, Filipe Antônio França da Silva, Kádima Nayara Teixeira
Vítor Hugo Sales da Mota, Kádima Nayara Teixeira, Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
Fabrício Freire de Melo, Breno Bittencourt de Brito, Filipe Antônio França da Silva, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
Author contributions: da Mota VHS, Freire de Melo F, and Teixeira KN contributed to study conceptualization, methodology, validation, and investigation and writing of the original draft; Freire de Melo F contributed to study conceptualization, methodology, and investigation, and manuscript review; de Brito BB and Silva FAFD contributed to study validation, visualization, and formal analysis and manuscript writing, review, and editing; Silva FAFD contributed to study validation, visualization, and formal analysis, manuscript writing, review, and editing, and supervision; Teixeira KN contributed to study conceptualization, methodology, and investigation, original draft writing, and supervision.
Institutional review board statement: This research was carried out in In silico models, not requiring an Institutional Review Board Statement.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data available.
Corresponding author: Kádima Nayara Teixeira, PhD, Adjunct Professor, Campus Toledo, Universidade Federal do Paraná, Road 182, km 320/321, Toledo 85.919-899, Paraná, Brazil. kadimateixeira@ufpr.br
Received: August 8, 2021 Peer-review started: August 8, 2021 First decision: September 2, 2021 Revised: September 16, 2021 Accepted: May 28, 2022 Article in press: May 28, 2022 Published online: June 24, 2022 Processing time: 317 Days and 10 Hours
ARTICLE HIGHLIGHTS
Research background
Mouse double minute 2 (MDM2) is the main negative regulator of tumor suppressor p53; in this context, the effective inhibition of MDM2 is an alternative for cancer treatments.
Research motivation
DS-3032B is an MDM2 antagonist, and its activity is known only empirically, so bioinformatics analyses can point to molecular characteristics of complex interaction.
Research objectives
To analyze, in silico, the interactions between the antagonist DS-3032B and MDM2 and infer the antineoplastic potential of the drug.
Research methods
The analysis of chemical bonds, interaction of the drug-protein complex, and its stability were done by molecular docking.
Research results
Molecular docking simulations between MDM2 chain A (PDB: 5SWK) and DS-3032B (CID: 73297272) in its protonabed form indicated a complex with significant affinity energy, -10.0 kcal/mol. The results indicate a stable complex, maintained by hydrophilic and hydrophobic bonds involving 16 amino acid residues of MDM2.
Research conclusions
DS-3032B is able to bind to MDM2 with high affinity and stability, suggesting therapeutic efficiency.
Research perspectives
Analyze the DS-3032B/MDM2 complex using molecular dynamics and verify the possibility of structural changes of the drug to increase its efficiency.
