鉴定和新型支架的动力学对抗Enterococcus faecium血清氧甲基转移酶酶:抗生素开发的潜在目标
Hassan H Alhassan1, Yasir S Alruwaili1, Sami I Alzarea2
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Al-Jouf Region, Saudi Arabia.
Journal of biomolecular structure & dynamics
|September 15, 2023
概括
计算方法确定了Enterococcus faecium血清氧甲基转移酶的新型抑制剂,这种酶是细菌生存的关键酶. 这些化合物显示为潜在的抗菌药物潜在的抗菌药物.
科学领域:
- 生物化学 生化学
- 计算化学的计算化学
- 药物发现 药物发现 药物发现
背景情况:
- 血清基甲基转移酶 (SHMT) 对于重要的生物合成途径至关重要.
- SHMT是抗癌,抗病毒和抗寄生虫剂的验证目标.
- 针对SHMT,特别是Enterococcus faecium的抗菌潜力仍未得到充分探索.
研究的目的:
- 以计算方式识别和描述Enterococcus faecium胺酸氧甲基转移酶的新型抑制剂.
- 评估潜在抗菌化合物的结合亲和力,稳定性和药物相似性.
主要方法:
- 基于结构的ASINEX抗菌库对E. faecium SHMT的虚拟查.
- 分子对接,分子动力学模拟和结合自由能计算 (MM/GBSA和MM/PBSA).
主要成果:
- 与对照分子相比,两种化合物Top-1_BDC_21204033和Top-2_BDC_20700155表现出强大的结合能 (分别为-9.3和-8.9卡路里/mol).
- 分子动力学模拟显示了化合物的稳定相互作用,Top-2_BDC_20700155显示了最高的稳定性 (结合的自由能量为-79.52到-82.63 kcal/mol).
- 化合物表现出有利的药物相似性,药物动力学特征,并预测是无毒和无变异性的.
结论:
- 这些已识别的化合物,特别是Top-2_BDC_20700155,是E. faecium SHMT.的有前途的抑制剂.
- 这些发现强调了SHMT作为一种可行的抗菌药物标.
- 实验验证是有必要的,以确认这些新型抗菌剂的治疗潜力.
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