Atomistic simulations suggest dietary flavonoids from Beta vulgaris (beet) as promising inhibitors of human angiotensin-converting enzyme and 2-alpha-adrenergic receptors in hypertension

MOTIVATION: Beta vulgaris (beet) is extensively reported for its antihypertensive activity. However, the mechanismunderpinning its antihypertensive activity is not well understood. In this study, we evaluated the in silico interactionsof 70 compounds derived from beta vulgaris against the active sites of angiotensin-converting enzyme (ACE) and alpha-adrenergic receptor (AR). RESULTS: Structure-based virtual screening against angiotensin-converting enzyme revealed that, Cochliophilin A (−9.0 Kcal/mol), Miraxanthin (−8.3 Kcal/mol), and quercimeritrin (−9.7 Kcal/mol) had lower docking scores than the reference lisinopril (−7.9 Kcal/mol). These compounds exhibited dual binding tendency as they also ranked top compounds upon screening against adrenergic receptor. The thermodynamic parameters computed from the resulting trajectories obtained from the 100 ns full atomistic molecular dynamics simulation revealed structural stability and conformational flexibility of the ligand–receptor complexes as indicated by the RMSD, RMSF, RoG, SASA, and H-bond calculations. The molecular mechanics with generalized Born and surface area solvation binding energy calculations revealed that the proteins exhibit considerable binding energy with the phytochemicals in a dynamic environment. Furthermore, the hit compounds possess good physicochemical properties and drug-likeness. Overall, cochliophilin and quercimeritrin are promising dual-target directed flavonoids from Beta vulgaris; and are suggested for further experimental and preclinical evaluation. AVAILABILITY AND IMPLEMENTATION: All data was provided in the manuscript.