In Silico Targeting and Structural Stabilization of LRRC66 by 3′,5,7-Trihydroxy-4′- methoxy flavanone A Computational Strategy for Therapeutic Modulation of Cardiac Remodeling
Keywords:
cardiovascular disease, drug design, LRRC66 gene, cardiac hypertrophy, molecular dockingAbstract
Cardiovascular diseases (CVDs) remain the leading cause of global mortality, responsible for approximately 20.5 million deaths in 2021. The impact of genetic alterations on protein stability was assessed using MUpro and I-Mutant 2.0. GalaxyRefine was used to refine the tertiary structure modeled by SWISS-MODEL, and validation was performed using Errat (overall quality factor 89.87) and Ramachandran plot analysis (93.4% residues in favored regions). Binding affinity was determined by molecular docking with AutoDock, and pharmacokinetic profiles were predicted by SwissADME. Finally, structural stability and B-factor flexibility were evaluated by molecular dynamics simulations using the iMODS approach. A docking binding affinity of −7.8 kcal/mol and a spontaneous binding free energy of −35.4 kcal/mol indicated strong interaction. 3',5,7-Trihydroxy-4'-methoxyflavanone optimized the structural dynamics of the solenoid domain by. We conclude that 3',5,7-Trihydroxy-4'-methoxyflavanone is a promising pharmacological approach for preventing heart failure and cardiac metabolic dysfunction by efficiently targeting and stabilizing the LRRC66 membrane sensor.
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