使用天然化合物在化中抑制IRF3-STING轴相互作用:使用分子对接,ADMET,分子动力学和MMPBSA方法的in-silico研究
Ashita Sood1, Mahesh Kulharia1
1Centre for Computational Biology and Bioinformatics, Central University of Himachal Pradesh, Dadroli, India.
In silico pharmacology
|December 11, 2024
概括
来自COCONUT数据库的天然化合物通过破坏IRF3-STING相互作用,显示出治疗病的潜力. 这些化合物可能为这种慢性肺病提供新的治疗途径.
科学领域:
- 计算化学和药物发现
- 分子建模和模拟分子模型
- 药理学和毒理学 药理学和毒理学
背景情况:
- 病是一种职业性肺病,通过cGAS-STING通路和IRF3激活引起持久性炎症.
- 准IRF3-STING相互作用是缓解症相关炎症的潜在策略.
研究的目的:
- 从COCONUT数据库中识别可以抑制IRF3-STING相互作用的自然化合物.
- 用IRF3.3评估这些化合物的类似药物的特性和结合稳定性.
主要方法:
- 利宾斯基的五项规则用于过自然化合物.
- 用分子对接和分子动力学模拟来评估化合物-蛋白质相互作用.
- 具有约束力的自由能量分解在IRF3.3中确定了关键的相互作用残留物.
主要成果:
- 选择的化合物表现出类似药物的特性,并与IRF3.3形成稳定的复合物.
- 分子动力学模拟证实了蛋白质-连接体复合体的结构完整性.
- 关键的IRF3残留物 (VAL295,ASP308,PRO324,ARG338) 被确定为化合物相互作用的关键,可能抑制IRF3-STING结合.
结论:
- 天然化合物CNP0310627 (burfenolide) 和CNP0200121 (psoralen) 通过调节cGAS-STING-IRF3通路,显示出对治疗病的希望.
- 这些化合物具有抗炎性质,可以被开发成新型疗法.
- 需要进一步的体外和体内研究来确认疗效和安全性.
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