Multi-Target Evaluation of Some Epicatechin Derivatives Against Critical Biological Targets: Molecular Docking, Efficiency Metrics, and Structural Dynamics
XXXII Symposium on Bioinformatics and Computer-Aided Drug Discovery (BCADD-2026), Moscow, Rusya, 19 - 21 Ekim 2026, ss.92, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: Moscow
- Basıldığı Ülke: Rusya
- Sayfa Sayıları: ss.92
- Recep Tayyip Erdoğan Üniversitesi Adresli: Evet
Özet
Epicatechin and its structurally modified derivatives have attracted considerable interest as potential bioactive scaffolds because of their diverse molecular recognition properties [1-3]. In the present study, twelve epicatechin derivatives were subjected to a comprehensive in silico investigation against a panel of pharmacologically relevant protein structures identified by Protein Data Bank (PDB) codes 6Y3C, 1UV5, 3IAI, 4RE3, 4D07, and 2OYE. Molecular docking calculations were performed using AutoDock Vina to comparatively evaluate the predicted binding affinities of the derivatives toward the selected protein targets. Among the investigated complexes, epicatechin derivative 8 ((2R,3R)-4-allyl-2-(3,4-dihydroxyphenyl) chroman-3,5,7-triol) exhibited the most favorable docking score against 4RE3, with a predicted binding affinity of −11.2 kcal mol-¹. The docking results were further subjected to a multidimensional ligand-efficiency assessment, including estimated inhibitory constants, ligand efficiency (LE), lipophilic ligand efficiency (LLE/LipE), size-independent ligand efficiency (SILE), Fit Quality, binding efficiency index (BEI), and surface efficiency index (SEI). These complementary metrics provided a more comprehensive evaluation of the relationship between molecular size, lipophilicity, structural characteristics, and predicted binding affinity than docking scores alone. The highest-ranked 8–4RE3 complex was subsequently investigated through two- and three-dimensional Ramachandran analyses and normal mode analysis to further characterize the conformational and structural properties of the docked protein–ligand system. In addition, bioavailability radar profiles were generated for molecule 8 epicatechin derivative, while SwissADME-based Boiled-Egg plots were used to assess their predicted gastrointestinal absorption and blood–brain barrier permeability characteristics. Collectively, the results provide an integrated computational profile of the investigated epicatechin derivatives and identify derivative 8 as the most promising compound within the studied series based on its predicted binding affinity and complementary ligand-efficiency characteristics.