通过机器学习的分子对接和分子动力学方法,揭示Berberine类似物作为潜在的Escherichia coli FtsZ抑制剂
Aditi Roy1,2, Anand Anbarasu3,4
1Medical and Biological Computing Laboratory, School of Bio-Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
Scientific reports
|April 26, 2025
概括
这项研究确定了ZINC000524729297和ZINC000604405393两种强效的柏柏林类似物,作为细菌细胞分裂蛋白FtsZ的潜在抑制剂. 这些化合物显示出开发新的抗菌剂来对抗抗药性药物耐药性的前景.
科学领域:
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
- 计算化学计算化学
背景情况:
- 细菌细胞分裂蛋白FtsZ对于细胞运动至关重要,也是抗菌药物开发的保存标.
- 抑制FtsZ会破坏原纤维的形成和细菌细胞分裂,提供对抗耐药细菌的策略.
研究的目的:
- 选柏柏林类似物以检测潜在的FtsZ抑制活性.
- 识别针对FtsZ的新型化合物,用于抗菌药物开发.
主要方法:
- 对1072种柏柏林类似物进行药物相似性和无毒性的选.
- 使用分子对接,对60种选择的化合物进行针对大肠杆菌FtsZ的虚拟查.
- 通过500 ns分子动力学 (MD) 模拟和MMPBSA分析验证对接结果.
主要成果:
- 两个化合物,ZINC000524729297和ZINC000604405393,对FtsZ.表现出强烈的结合亲和力.
- MD模拟和MMPBSA分析证实了FtsZ-连接体复合物的稳定性和低结合能.
- ZINC000524729297和ZINC000604405393显示了增强的形状稳定性和与FtsZ.的强烈相互作用.
结论:
- ZINC000524729297和ZINC000604405393被确定为针对细菌FtsZ的强有力的化合物.
- 这些化合物有潜力开发新的抗菌剂来克服耐药性.
- 建议进行进一步的实验验证,以确认这些化合物的疗效.
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