在日本脑炎病毒中小分子对NS5蛋白抑制的结构和能量分析,使用机器学习和定向分子动力学方法
Abdulfattah Y Alhazmi1, Farhan R Khan2, Zia Ur Rehman3
1Pharmaceutical Practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
Journal of biomolecular structure & dynamics
|February 26, 2024
概括
研究人员对749种抗病毒分子进行了选,针对日本脑炎病毒 (JEV) 非结构蛋白5 (NS5). 化合物123519051表现出强大的结合和抑制JEV NS5的潜力,提供了一个有前途的治疗途径.
科学领域:
- 病毒学 病毒学
- 计算化学计算化学
- 药物发现 药物发现 药物发现
背景情况:
- 日本脑炎 (JE) 是一种严重的病毒性疾病,影响全球数百万人,特别是在发展中国家.
- 非结构蛋白5 (NS5) 是日本脑炎病毒 (JEV) 的保存和必需蛋白质.
研究的目的:
- 使用计算选方法识别JEV NS5蛋白的潜在抑制剂.
- 评估已识别的化合物与目标NS5蛋白的结合亲和力和稳定性.
主要方法:
- 基于机器学习的虚拟查749个抗病毒分子针对JEV NS5.
- 采用了分子对接,分子动力学模拟,MM/GBSA,主要组件分析和引导分子动力学.
- 对键相互作用,结合的自由能量和复杂稳定性的分析.
主要成果:
- 三种化合物 (24360,123519051和213039) 的结合能低于对照组 (S-Adenosyl-L-homocysteine) 的结合能.
- 化合物123519051显示了与NS5的最低结合自由能量 (-89kJ/mol) 和稳定的复合物形成,包括与Gly111.11的关键键键.
- 定向分子动力学证实了123519051的稳定复合体形成,其分离幅度很高.
结论:
- 化合物123519051被确定为JEV NS5蛋白的强有力的结合剂.
- 这种化合物显示出抑制NS5功能的潜力,并可能成为开发新型日本脑炎治疗药物的领头羊.
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