关于万科米辛和提科普拉宁与细菌细胞壁结尾结合的第一原则调查
Jung-Goo Lee1, Celeste Sagui, Christopher Roland
1Department of Physics, The North Carolina State University, Raleigh, North Carolina 27695-82802, USA.
Journal of the American Chemical Society
|July 9, 2004
概括
与糖类抗生素结合的抗万科米辛耐药肠内球菌 (VRE) 与d-Ala-d-Lac相比,与d-Ala-d-Ala相比较弱. 这种差异主要是由于VRE复合体中的氧-氧单对排斥.
科学领域:
- 生物化学 生物化学
- 微生物学 微生物学
- 计算化学的计算化学
背景情况:
- 抗素耐药性肠球菌 (VRE) 的出现需要了解糖抗生素耐药性机制.
- 细菌细胞壁的末端,特别是VRE中的d-Ala-d-Lac和非VRE中的d-Ala-d-Ala,是科米辛和提科普拉宁等抗生素的关键标.
研究的目的:
- 为了研究万科米辛和提科普拉宁与细菌细胞壁的结合亲和力.
- 阐明控制抗生素与d-Ala-d-Lac (VRE) 与d-Ala-d-Ala (非VRE) 结合的分子相互作用.
主要方法:
- 使用了广泛的第一原则计算调查.
- 分析的重点是抗生素与两个不同的细胞壁末端之间的结合能量和相互作用动态.
主要成果:
- 范科米辛和提科普拉宁与d-Ala-d-Ala的结合明显比与d-Ala-d-Lac的结合强大,约为3-5kcal/mol.
- 对d-Ala-d-Lac的结合亲和力降低主要归因于抗生素/d-Ala-d-Lac复合体内的氧-氧单对排斥.
结论:
- 计算结果为范科米辛和提科普拉宁对VRE的有效性降低提供了分子基础.
- 这项研究的结果与最近关于抗生素耐药性的实验观察结果一致并解释了它们.
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