通过基于网络的查方法,分子对接和模拟来识别潜在的分子标和用于结核病的重定向药物
Arunika Krishnan1, Faez Iqbal Khan2, Sudarkodi Sukumar3
1School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai, India.
Journal of biomolecular structure & dynamics
|November 10, 2023
概括
耐药结核病是一个全球性的挑战. 研究人员将embB确定为细胞壁中的关键蛋白质,并发现阿齐尔沙坦和二欧戈他胺可能是结核病的潜在新疗法.
科学领域:
- 微生物学 微生物学
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
背景情况:
- 耐药结核病 (TB) 构成了严重的全球健康威胁,阻碍了控制工作.
- * Mycobacterium tuberculosis * 的动态细胞壁外对其生存至关重要,并代表了新型治疗方法的有希望的目标.
- 蛋白与蛋白相互作用网络 (PPIN) 对于了解疾病机制和识别药物点至关重要.
研究的目的:
- 在* Mycobacterium tuberculosis*细胞壁生物合成中使用蛋白质-蛋白质相互作用网络 (PPIN) 方法识别关键蛋白质.
- 选潜在的药物重新定位候选人,以准已识别的关键蛋白质,embB.
- 通过计算验证选择的候选药物的结合效果和稳定性与embB.
主要方法:
- 使用STRING数据库构建细胞壁生物合成蛋白的PPIN.
- 在CytoNCA中使用拓测量 (间距,接近,程度,自身向量) 来识别embB作为关键蛋白质.
- 使用施罗丁格套件对FDA批准的药物进行高通量虚拟查,以防 embB (PDB ID: 7BVF),然后进行分子对接,结合自由能计算和 100 ns 分子动力学模拟.
主要成果:
- 蛋白质embB被确定为 * Mycobacterium 结核病* 细胞壁生物合成 PPIN 的关键枢纽.
- 虚拟查确定了阿齐尔沙坦和二欧戈他胺作为顶级药物重新定位候选药物,具有有利的对embB的结合特性.
- 分子动力学模拟证实了embB和阿齐尔沙坦和二欧戈他胺之间的稳定复合物形成.
结论:
- 阿齐尔沙坦和二欧戈他胺显示出潜力,作为治疗结核病治疗的新型治疗分子,通过向embB.
- 这些发现需要进一步进行"体外"和"体内"实验验证,以确认它们对"Mycobacterium tuberculosis"的有效性.
- 这项研究强调了PPIN分析和药物重定向在识别新的抗结核病候选药物的有用性.
关键词:
结核病菌菌菌的结核病菌的结核病菌.阿拉伯基转移酶是什么?有约束力的自由能源.细胞景观 (cytoscape) 是一个图像.药物重用是为了改变药物的用途.这就是为什么embBB embBB.乙胺乙醇的使用方法分子动力学模拟模拟蛋白质与蛋白质相互作用网络.更多相关视频
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