DFT calculations of electronic structure evaluation and intermolecular interactions of p53-derived peptides with cytotoxic effect on breast cancer
Por:
Barrientos-Salcedo, Carolina, Lara-Rodriguez, Maricarmen, Campos-Fernandez, Linda, Legorreta-Herrera, Martha, Soto-Cruz, Isabel, Soriano-Correa, Catalina
Publicada:
1 ago 2021
Categoría:
Physical and theoretical chemistry
Resumen:
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.
Filiaciones:
Barrientos-Salcedo, Carolina:
Soriano-Correa, C (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac Sintesis & Farmacol Mol Inte, Iztapalapa 09230, Mexico. Barrientos-Salcedo, Carolina, Univ Veracruzana, Fac Bioanalisis Campus Veracruz, Lab Quim Med & Quimiogenom, Veracruzana 91700, Veracruz, Mexico. Lara-Rodriguez, Maricarmen
Lara-Rodriguez, Maricarmen:
Soriano-Correa, C (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac Sintesis & Farmacol Mol Inte, Iztapalapa 09230, Mexico. Barrientos-Salcedo, Carolina, Univ Veracruzana, Fac Bioanalisis Campus Veracruz, Lab Quim Med & Quimiogenom, Veracruzana 91700, Veracruz, Mexico. Lara-Rodriguez, Maricarmen
Campos-Fernandez, Linda:
Soriano-Correa, C (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac Sintesis & Farmacol Mol Inte, Iztapalapa 09230, Mexico. Barrientos-Salcedo, Carolina, Univ Veracruzana, Fac Bioanalisis Campus Veracruz, Lab Quim Med & Quimiogenom, Veracruzana 91700, Veracruz, Mexico. Lara-Rodriguez, Maricarmen
Legorreta-Herrera, Martha:
Soriano-Correa, C (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac Sintesis & Farmacol Mol Inte, Iztapalapa 09230, Mexico. Barrientos-Salcedo, Carolina, Univ Veracruzana, Fac Bioanalisis Campus Veracruz, Lab Quim Med & Quimiogenom, Veracruzana 91700, Veracruz, Mexico. Lara-Rodriguez, Maricarmen
Soto-Cruz, Isabel:
Soriano-Correa, C (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac Sintesis & Farmacol Mol Inte, Iztapalapa 09230, Mexico. Barrientos-Salcedo, Carolina, Univ Veracruzana, Fac Bioanalisis Campus Veracruz, Lab Quim Med & Quimiogenom, Veracruzana 91700, Veracruz, Mexico. Lara-Rodriguez, Maricarmen
Soriano-Correa, Catalina:
Soriano-Correa, C (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac Sintesis & Farmacol Mol Inte, Iztapalapa 09230, Mexico. Barrientos-Salcedo, Carolina, Univ Veracruzana, Fac Bioanalisis Campus Veracruz, Lab Quim Med & Quimiogenom, Veracruzana 91700, Veracruz, Mexico. Lara-Rodriguez, Maricarmen
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