通过通过计算药物发现来向Eis蛋白来抑制Mycobacterium结核病毒性和耐药性
Geethu S Kumar1, Amaresh Kumar Sahoo2, Nishant Ranjan3
1Centre for Development of Biomaterials and Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, 201310, India.
Molecular diversity
|August 3, 2024
概括
研究人员选了天然化合物,以寻找抗药结核病的新疗法. 他们发现了几种化合物,它们强烈地与Eis蛋白结合,这是恢复抗生素有效性的关键目标.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 结核病 (TB) 构成了重大的全球卫生挑战,多种耐药菌株的兴起加剧了这一问题.
- 来自Mycobacterium tuberculosis的增强细胞内存活 (Eis) 蛋白通过乙化使氨基糖类抗生素失活,从而阻碍了它们的治疗疗效.
- 开发新的策略来克服结核病的抗生素耐药性至关重要.
研究的目的:
- 为了确定可以抑制Mycobacterium结核病Eis蛋白的天然化合物.
- 探索潜在的治疗药物,以打击耐药结核病,通过准Eis.
主要方法:
- 从子数据库中对406,747种天然化合物的计算选与Eis蛋白进行了对比.
- 分子对接和MM/GBSA重组以评估结合能量和亲和力.
- 分子动力学 (MD) 模拟,具有约束力的自由能量计算,主要组件分析 (PCA) 和自由能量景观分析以评估复杂的稳定性.
主要成果:
- 五种天然化合物 (CNP0187003,CNP0176690,CNP0136537,CNP0398701,CNP0043390) 显示出与Eis蛋白具有很高的结合亲和力.
- 在MD模拟中,Eis-CNP0043390复合体表现出最高的稳定性,其次是Eis-CNP0187003和Eis-CNP0176690.
- 这些顶级化合物形成了显著的键和与Eis蛋白的相互作用.
结论:
- 已识别的天然化合物显示出作为Eis蛋白的抑制剂的潜力.
- 这些发现支持使用计算方法来发现抗药结核病的新型候选药物.
- 向Eis蛋白提供了一种有希望的策略,以恢复对抗耐药结核病菌株的氨基糖化抗生素活性.
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