准XGHPRT酶来管理Helicobacter pylori诱导的胃癌:一个基于机器学习,人工智能和生物物理学的多方位研究
1Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia.
Saudi journal of biological sciences
|February 26, 2024
概括
新型化合物CHEMBRIDGE-10000196,CHEMBRIDGE-10000295和CHEMBRIDGE-10000955在通过向细菌核酸合成中的关键参与者XGHPRT酶来抑制Helicobacter pylori方面表现有前途.
科学领域:
- 微生物学 微生物学
- 计算化学计算化学
- 药物发现 药物发现 药物发现
背景情况:
- 杆菌感染影响全球一半以上的人口,并与胃癌有关.
- 在H. pylori的抗生素耐药性需要识别新的治疗点.
- 抑制细菌核酸生物合成是打击细菌繁殖的可行策略.
研究的目的:
- 确定XGHPRT酶的新型抑制剂,这对于H. pylori中的RNA和DNA前体合成至关重要.
- 用计算方法评估潜在药物候选物的结合亲和力和稳定性.
主要方法:
- 机器学习,人工智能和基于生物物理学的软件被用于虚拟查.
- 进行了对接模拟,以预测与XGHPRT酶的结合分数和相互作用.
- 分子动力学模拟和MM-GBSA/MM-PBSA计算评估了对接复合体的稳定性和结合能.
主要成果:
- 鉴定出CHEMBRIDGE-10000196,CHEMBRIDGE-10000295和CHEMBRIDGE-10000955是XGHPRT的强有力的结合剂,分别得分为-14.20,-13.64和-12.08 kcal/mol. 这两种结合剂具有很强的结合作用.
- 这些化合物在酶活性部位内与关键氨基酸残留物 (Met33,Arg34,Ala57,Asp92,Ser93,Gly94) 形成强烈的相互作用.
- 停靠的复合体表现出稳定的动力和显著的结合能,其中主要的贡献来自静电和范德瓦尔斯力.
结论:
- 已识别的化合物CHEMBRIDGE-10000196,CHEMBRIDGE-10000295和CHEMBRIDGE-10000955,显示出作为H. pylori XGHPRT.抑制剂的显著潜力.
- 这些分子需要进一步进行实验研究,以确定它们对H. pylori感染的治疗效果.
关键词:
在ADMET中,ADMET的属性是:在Helicobacter Pylori的研究中,模拟分子动力学模拟虚拟选是一个虚拟的选.桑提因 - 瓜宁 - 桑提因 phosphoribosyltransferase 转移酶更多相关视频
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