Abstract

FLORES-HOLGUIN, Norma; FRAU, Juan  and  GLOSSMAN-MITNIK, Daniel. Computational nanochemistry study of the alisporivir and cyclosporin antimicrobial peptides through conceptual DFT-based computational peptidology and pharmacokinetics. Mundo nano [online]. 2022, vol.15, n.29, e00052.  Epub Aug 15, 2022. ISSN 2448-5691.  https://doi.org/10.22201/ceiich.24485691e.2022.29.69725.

This paper reports the results of a computational nanochemistry study of the chemical reactivities and bioactivity properties of two antimicrobial peptides using a CDFT-based computational peptidology (CDFT-CP) methodology, which is derived from the combination of the chemical reactivity descriptors derived from conceptual density functional theory (CDFT) and some cheminformatics tools useful in the design of therapeutic drugs. This is complemented by an examination of the bioactivity and pharmacokinetics indices of the peptides in relation to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. These findings provide further evidence of the superiority of the MN12SX density functional in fulfilling the Janak and ionization energy theorems using an earlier proposed KID methodology for validation. This has proven to be beneficial in accurately predicting CDFT indices, which is of help in the understanding of the chemical reactivity. The computational pharmacokinetics study revealed the potential ability of both cyclopeptides as therapeutic drugs through the interaction with different target receptors. The ADMET indices confirmed this assertion through the absence of toxicity and good absorption and distribution properties.

Keywords : alisporivir; cyclosporin A; chemical reactivity theory; conceptual DFT; global and local reactivity descriptors; pKa; bioavailability; bioactivity scores; ADMET.