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DFT calculations of electronic structure evaluation and intermolecular interactions of p53-derived peptides with cytotoxic effect on breast cancer

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Abstract

Cancer is the second cause of death worldwide, leading to the high mortality rate, breast cancer. It is a global health problem due to its severe clinical manifestations and it is also related to a great variety of genetic and environmental risk factors with which it is associated. The knowledge of molecules involved in tumor processes allows identifying therapeutic targets to develop new drugs. Computational chemistry allows exploring and analyzing molecules at the atomic level with therapeutic functionality. In this work, we evaluate and analyze the stability, the physicochemical properties and chemical reactivity of p53-derived peptides with cytotoxic effect on breast cancer, using quantum-chemical descriptors: chemical hardness, ionization potential, electrophilicity index, atomic charges, and molecular orbitals at the DFT-B3LYP level in aqueous solution, and its intermolecular interactions by molecular docking. The results showed that hydrophobic amino acids improve the cytotoxic effect. Peptides with three mutations are less stable than peptides with two mutations; hence, a more stable peptide does not necessarily imply a high therapeutic effect. Residues: F19, W22, W23 and their respective atomic charges of nitrogen atoms, and its hydrogens (NH) of the amide groups of these amino acids are determinants for the interactions, also contribute to the stability and chemical reactivity and consequently, to the binding affinity of p53 derivative peptides with MDM2 protein.

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Acknowledgements

The authors are grateful to the Dirección General de Cómputo y de Tecnologías de Información y Comunicación (DGCTIC) at the Universidad Nacional Autónoma de México (UNAM) for allocation of computer time in the supercomputer (Miztli, LANCAD-UNAM-DGTIC-203). This research was supported by DGAPA-UNAM grant PAPIIT-IN230419. CBS, gratefully acknowledged the computing time granted by LANCAD and CONACYT on the supercomputer Yoltla/Miztli/Xiuhcoatl at LSVP UAM-Iztapalapa/ DGTIC UNAM/CGSTIC CINVESTAV.

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Authors and Affiliations

  1. Laboratorio de Química Médica y Quimiogenómica, Facultad de Bioanálisis Campus Veracruz, Universidad Veracruzana, C.P. 91700, Veracruz, Mexico

    Carolina Barrientos-Salcedo

  2. Unidad de Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), C.P. 09230, Iztapalapa, Ciudad de Mexico, Mexico

    Maricarmen Lara-Rodríguez, Linda Campos-Fernández, Martha Legorreta-Herrera & Catalina Soriano-Correa

  3. Laboratorio de Oncología Molecular, Unidad de Investigación en Diferenciación Celular y Cáncer, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), 09230, Iztapalapa, Ciudad de Mexico, Mexico

    Isabel Soto-Cruz

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  1. Carolina Barrientos-Salcedo
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Barrientos-Salcedo, C., Lara-Rodríguez, M., Campos-Fernández, L. et al. DFT calculations of electronic structure evaluation and intermolecular interactions of p53-derived peptides with cytotoxic effect on breast cancer. Theor Chem Acc 140, 121 (2021). https://doi.org/10.1007/s00214-021-02822-0

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