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

Q4 Medicine
Georgian medical news Pub Date : 2024-12-01
N Mousa, A Attia, K Ali
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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.

设计,分子对接,分子动力学和评估靶向β -2肾上腺素能受体的哮喘治疗新配体。
本研究探讨了靶向β -2肾上腺素能受体(β2AR)的新型配体的设计和分子对接,β -2肾上腺素能受体是参与支气管收缩和哮喘调节的关键蛋白。利用分子对接模拟,我们评估了合成的化合物(包括化合物1、化合物5和参比药物沙丁胺醇)对β2AR的结合亲和力。对接研究使用GOLD软件进行,并分析结合相互作用,以确定负责配体结合和受体激活的关键残基。结果表明,所有被测化合物,特别是化合物1和化合物5,与β2AR结合较强,结合能与沙丁胺醇相当。关键残基如SER 207、PHE 289、LYS 305和ASP 192在稳定受体-配体相互作用中发挥了重要作用。合成的化合物中NO2和NC等官能团的存在增强了它们的亲和力,表明结构修饰可以优化β2AR的结合。这些发现为β 2ar配体相互作用的分子机制提供了有价值的见解,并突出了化合物1和5作为进一步开发为哮喘治疗β2激动剂的有希望的候选者的潜力。沙丁胺醇作为一种成熟的β2激动剂,可作为评估新型配体疗效的基准,证实了设计具有更高效力和选择性的β 2ar靶向治疗药物的可行性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Georgian medical news
Georgian medical news Medicine-Medicine (all)
CiteScore
0.60
自引率
0.00%
发文量
207
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