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Evaluation of Docking Machine Learning and Molecular Dynamics Methodologies for DNA-Ligand Systems.
de Oliveira, Tiago Alves; Medaglia, Lucas Rolim; Maia, Eduardo Habib Bechelane; Assis, Letícia Cristina; de Carvalho, Paulo Batista; da Silva, Alisson Marques; Taranto, Alex Gutterres.
Afiliação
  • de Oliveira TA; Department of Bioengineering, Federal University of Sao Joao del-Rei, Praça Dom Helvecio, 74, Fabricas, Sao Joao del-Rei 36301-1601, MG, Brazil.
  • Medaglia LR; Federal Center for Technological Education of Minas Gerais, Department of Informatics, Management and Design, CEFET MG, Campus Divinopolis, Rua Alvares de Azevedo, 400, Bela Vista, Divinopolis 35503-822, MG, Brazil.
  • Maia EHB; Department of Bioengineering, Federal University of Sao Joao del-Rei, Praça Dom Helvecio, 74, Fabricas, Sao Joao del-Rei 36301-1601, MG, Brazil.
  • Assis LC; Federal Center for Technological Education of Minas Gerais, Department of Informatics, Management and Design, CEFET MG, Campus Divinopolis, Rua Alvares de Azevedo, 400, Bela Vista, Divinopolis 35503-822, MG, Brazil.
  • de Carvalho PB; Department of Bioengineering, Federal University of Sao Joao del-Rei, Praça Dom Helvecio, 74, Fabricas, Sao Joao del-Rei 36301-1601, MG, Brazil.
  • da Silva AM; Feik School of Pharmacy, University of the Incarnate Word, 4301 Broadway, San Antonio, TX 78209, USA.
  • Taranto AG; Federal Center for Technological Education of Minas Gerais, Department of Informatics, Management and Design, CEFET MG, Campus Divinopolis, Rua Alvares de Azevedo, 400, Bela Vista, Divinopolis 35503-822, MG, Brazil.
Pharmaceuticals (Basel) ; 15(2)2022 Jan 22.
Article em En | MEDLINE | ID: mdl-35215245
DNA is a molecular target for the treatment of several diseases, including cancer, but there are few docking methodologies exploring the interactions between nucleic acids with DNA intercalating agents. Different docking methodologies, such as AutoDock Vina, DOCK 6, and Consensus, implemented into Molecular Architect (MolAr), were evaluated for their ability to analyze those interactions, considering visual inspection, redocking, and ROC curve. Ligands were refined by Parametric Method 7 (PM7), and ligands and decoys were docked into the minor DNA groove (PDB code: 1VZK). As a result, the area under the ROC curve (AUC-ROC) was 0.98, 0.88, and 0.99 for AutoDock Vina, DOCK 6, and Consensus methodologies, respectively. In addition, we proposed a machine learning model to determine the experimental ∆Tm value, which found a 0.84 R2 score. Finally, the selected ligands mono imidazole lexitropsin (42), netropsin (45), and N,N'-(1H-pyrrole-2,5-diyldi-4,1-phenylene)dibenzenecarboximidamide (51) were submitted to Molecular Dynamic Simulations (MD) through NAMD software to evaluate their equilibrium binding pose into the groove. In conclusion, the use of MolAr improves the docking results obtained with other methodologies, is a suitable methodology to use in the DNA system and was proven to be a valuable tool to estimate the ∆Tm experimental values of DNA intercalating agents.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Pharmaceuticals (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Pharmaceuticals (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça