Pharmacophore modeling of selective interaction of ligands with cytochrome P450 isoforms

Abstract

Cytochrome P450 (CYP) enzymes are essential players in drug metabolism and exhibit pronounced selectivity toward specific substrates and inhibitors. This selectivity arises from structural differences in
the active sites of various CYP isoforms.
The aim of the study - to establish the reasons for the selective interaction of substrates and inhibitors with different CYP isoforms by identifying the structural and functional features of the active site of
enzymes that cause differences in their specificity.
In this study, pharmacophore modeling approaches were applied to identify key molecular interactions governing ligand selectivity across CYP isoforms. Pharmacophore models were constructed
based on the spatial and electronic features of known substrates and inhibitors. The analysis revealed critical pharmacophoric elements responsible for isoform-specific binding.
The models obtained can be used to predict metabolic pathways, guide the design of selective inhibitors, and support early-stage drug development and screening.