In Silico Pharmacokinetics, ADMET Study and Conceptual DFT Analysis of Two Plant Cyclopeptides Isolated From Rosaceae as a Computational Peptidology Approach

Front Chem. 2021 Aug 12;9:708364. doi: 10.3389/fchem.2021.708364. eCollection 2021.

Abstract

This research presents the outcomes of a computational determination of the chemical reactivity and bioactivity properties of two plant cyclopeptides isolated from Rosaceae through the consideration of Computational Peptidology (CP), a protocol employed previously in the research of similar molecular systems. CP allows the prediction of the global and local descriptors that are the integral foundations of Conceptual Density Functional Theory (CDFT) and which could help in getting in the understanding of the chemical reactivity properties of the two plant cyclopeptides under study, hoping that they could be related to their bioactivity. The methodology based on the Koopmans in DFT (KID) approach and the MN12SX/Def2TZVP/H2O model chemistry has been successfully validated. Various Chemoinformatics tools have been used to improve the process of virtual screening, thus identifying some additional properties of these two plant cyclopeptides connected to their ability to behave as potentially useful drugs. With the further objective of analyzing their bioactivity, the CP protocol is complemented with the estimation of some useful parameters related to pharmacokinetics, their predicted biological targets, and the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) parameters related to the bioavailability of the two plant cyclopeptides under study are also reported.

Keywords: ADMET; Koopmans in density functional theory; conceptual density functional theory; pharmacokinetics; plant cyclopeptides.