Computational Exploration of Berrie’s Anthocyanin as a Novel Angiotensin-Converting Enzyme Inhibitor

Hypertension, a significant global health concern, is managed by targeting Angiotensin-Converting Enzyme (ACE). Anthocyanins, natural flavonoids present in berries, have antioxidant and cardioprotective properties, suggesting their potential as ACE inhibitors. This study assessed twenty anthocyanin derivatives from berries as novel ACE inhibitors by a comprehensive in silico approach, comparing them to the standard drug Moexipril. The computational pipeline included molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) profiling, Density Functional Theory (DFT) computations, extensive molecular dynamics (200 ns) and Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) binding free energy calculations. Initially, candidates exhibiting favorable binding energies (−9.9 kcal/mol) in comparison to Moexiprill (−8.9 kcal/mol) were identified using molecular docking as Procyanidin B2 and Keracyanin Cation. Subsequent ADMET predictions indicated that these lead compounds exhibit favorable drug-like properties and toxicity profiles. MD simulations of the ACE-ligand complexes, encompassing RMSD, RMSF, Rg, SASA, Principal Component Analysis (PCA) and Free Energy Landscape (FEL), elucidated their conformational stability and dynamics. DFT computations demonstrated the intrinsic electronic stability of Procyanidin B2 ([Formula: see text] 0.19655 eV). Significantly, MM/PBSA calculations yielded revised binding affinity estimates, identifying Keracyanin ([Formula: see text]bind [Formula: see text]29.89 kcal/mol) as the superior binder, surpassing Moexiprill ([Formula: see text]bind [Formula: see text]18.66 kcal/mol), whereas Procyanidin B2 had a low binding affinity ([Formula: see text]bind [Formula: see text]13.20 kcal/mol). Collectively, these computational investigations indicate that anthocyanins, notably Keracyanin, exhibit significant promise as ACE inhibitors due to their favorable binding affinities and interaction patterns. Procyanidin B2 also has excellent molecular stability and favorable ADMET properties. These findings underscore the potential of berry anthocyanins in hypertension management and necessitate further in vitro and in vivo experimental validation.