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Molecular Modeling Approach to Investigate the Intercalation of Phthalates and Their Metabolites in DNA Macromolecules

2019; American Scientific Publishers; Volume: 16; Issue: 2 Linguagem: Inglês

10.1166/jctn.2019.8110

1546-1963

Tatiane P. Rodrigues, Jorddy Neves Cruz, Tiago S. Arouche, Tais S. S. Pereira, Wanessa A. Costa, Sebastião Gomes Silva, N. C. Raul, Mozaniel Santana de Oliveira, Antônio Maia de Jesus Chaves Neto,

Advanced biosensing and bioanalysis techniques

Recent studies have reported that phthalates are capable of causing mutations and other changes in the genetic material. This study aimed to investigate the molecular interactions between phthalate di(2-ethylhexyl) phthalate (DEHP) and its metabolites monobutyl phthalate (MBP) and monoethyl phthalate (MEP), interacting with DNA. The research was conducted using molecular modeling techniques such as molecular docking and molecular dynamics simulations. Molecular docking revealed that the DEHP, MBP, and MEP are able to establish hydrogen interactions with various nucleotide bases. Molecular dynamics simulations revealed that these molecules interacted with the DNA, and the binding free energy results demonstrated that the DNA-ligand interaction has favorable free energy. The values for free binding energy were as follows: DNA–DEHP, –21.66 kcal/mol; DNA–MBP, –17.29 kcal/mol; and DNA–MEP, –20.13 kcal/mol. For these three systems, the contributions of van der Waals, electrostatic, and nonpolar solvation energy were favorable for the interaction. The van der Waals interactions contributed the major energy to the intercalation of the binders.