Resumo

PENA, Ángela et al. Influence of Mg²⁺ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integrase. Univ. Sci. [online]. 2012, vol.17, n.1, pp.5-15. ISSN 0122-7483.

Objective. Using molecular simulation, we studied the influence of Mg²⁺ ions on the binding mode of HTLV-I Integrase (IN) catalytic domain (modeled by homology) with the 3,5- Dicaffeoylquinic Acid (DCQA). HTLV-I Integrase homology model was built using template-like crystallographic data of the IN catalytic domain solved for Avian Sarcoma Virus (VSA, pdb: 1VSD). Materials and methods. In order to analyze the role of Mg²⁺ in the interaction or coupling between 3,5-DCQA and Integrase, three models were created: i) in the absence of Mg²⁺ ions, ii) with a Mg²⁺ ion coordinated at Asp15 and Asp72 and iii) model with two Mg²⁺ ions coordinated at Asp15-Asp72 and Asp72-Glu108. Coupling force and binding free energy between 3,5-DCQA and HTLV-I IN were assessed in the three models. Results. The lowest docking score and free energy binding were obtained for the second model. Mg²⁺ ion strongly affected the coupling of the inhibitor 3,5-DCQA with HTLV-I catalytic domain of Integrase, thus revealing a strong interaction in the ligand-protein complex regardless of the ligand-catalytic interaction sites for all three models. Conclusion. Altogether, these results strengthen the hypothesis that the presence of one Mg²⁺ ion could enhance the interaction in the complex by decreasing free energy, therefore increasing the affinity. Moreover, we propose 3,5-DCQA as an important pharmacophore in the rational design of new antiretroviral drugs.

Palavras-chave : 3,5 -Dicaffeoylquinic Acid; Human T-Lymphotropic Type I (HTLV-1); Integrase (IN); Homology Model; Molecular Docking; Binding Free Energy; Mg²⁺ Ions.

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