An integrated molecular modeling protocol for drug screening based on conceptual density functional theory and chemoinformatics for the study of marine cyclopeptides

Abstract

An integrated molecular modeling protocol resulting from the combination of conceptual density functional theory (CDFT) chemical reactivity descriptors with several chemoinformatics tools has been used for the study of the chemical reactivity and bioactivity properties of a group of marine cyclic peptides. CP-CDFT is a branch of computational chemistry and molecular modeling dedicated to the study of peptides. The protocol allowed the estimation of the CDFT-based reactivity indices together with the associated physicochemical parameters that can help to identify the ability of the studied peptides to behave as potential useful drugs. This was complemented with an analysis of the bioactivity and pharmacokinetics parameters related to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. Some examples related to the ability of the CDFT-based chemical reactivity descriptors for the prediction of the pKas of the peptides as well as their potential as AGE inhibitors are also presented.

Keywords: ADMET; Computational peptidology; Computational pharmacokinetics; Conceptual DFT; KID (Koopmans In DFT); Neamphamides A–D.