DESIGN, MOLECULAR DOCKING, MOLECULAR DYNAMICS, AND EVALUATION OF NOVEL LIGANDS TARGETING BETA-2 ADRENERGIC RECEPTOR FOR ASTHMA THERAPEUTICS.

Abstract

This study investigates the design and molecular docking of novel ligands targeting the beta-2 adrenergic receptor [β2AR], a critical protein involved in bronchoconstriction and asthma regulation. Utilizing molecular docking simulations, we evaluated the binding affinities of synthesized compounds, including compound 1, compound 5, and the reference drug salbutamol, against β2AR. The docking studies were conducted using GOLD software, and binding interactions were analyzed to identify key residues responsible for ligand binding and receptor activation. The results revealed that all tested compounds, particularly compound 1 and compound 5, demonstrated strong binding to the β2AR, with binding energies comparable to salbutamol. Key residues such as SER 207, PHE 289, LYS 305, and ASP 192 played significant roles in stabilizing the receptor-ligand interactions. The presence of functional groups like NO2 and NC in the synthesized compounds enhanced their affinity, suggesting that structural modifications could optimize β2AR binding. These findings provide valuable insights into the molecular mechanisms underlying β2AR-ligand interactions and highlight the potential of compounds 1 and 5 as promising candidates for further development into β2 agonists for asthma treatment. Salbutamol, as a well-established β2 agonist, served as a benchmark for evaluating the efficacy of the novel ligands, confirming the feasibility of designing β2AR-targeting therapeutics with improved potency and selectivity.