1. DFT calculations of electronic structure evaluation and intermolecular interactions of p53-derived peptides with cytotoxic effect on breast cancer
- Author
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Isabel Soto-Cruz, Catalina Soriano-Correa, Carolina Barrientos-Salcedo, Linda Campos-Fernández, Martha Legorreta-Herrera, and Maricarmen Lara-Rodríguez
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,chemistry ,Computational chemistry ,Amide ,Intermolecular force ,Electrophile ,Molecule ,Peptide ,Molecular orbital ,Physical and Theoretical Chemistry ,Derivative (chemistry) ,Amino acid - 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.
- Published
- 2021
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