从结合点移动水的热力学及其对超分子和生物分子亲和力的贡献
Jeffry Setiadi1, Frank Biedermann2, Werner M Nau3
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9255 Pharmacy Lane, La Jolla, California, 92093, USA.
Angewandte Chemie (International ed. in English)
|June 4, 2025
概括
水位移显著影响非共价结合,作为一个关键的驱动力,而不是旁观者. 即使是"不利"的腔水也可以在宿主-客人系统中增强高亲和度结合.
科学领域:
- 超分子化学 超分子化学
- 计算化学的计算化学
- 生物物理化学 生物物理化学
背景情况:
- 水在非共价结合中的作用是超分子化学和药物设计中的长期争论.
- 了解水的影响对于设计有效的宿主-客人系统和治疗剂至关重要.
研究的目的:
- 为了调查水是被动旁观者还是非共价结合中的积极驱动者.
- 量化水位移在宿主与客人的相互作用中的能量贡献.
- 解决稳定但热力学上不利的空腔水的悖论.
主要方法:
- 利用分子动力学模拟理想化的宿主-客系统.
- 采用黄[8]uril基宏循环宿主模型,具有不同的水相互作用能量.
- 分析了从绑定站点的水位移的自由能源成本.
主要成果:
- 计算的水位移的自由能量成本在0到+37kcalmol-1之间,显著影响了结合亲和力.
- 无论是水密度还是过量的化学潜力都不能可靠地预测空洞水的热力学优势.
- 证实"不利"的结合点水可以促进高亲和度结合.
结论:
- 水位移是一个关键因素,经常驱动非共价结合.
- 这项研究解决了稳定但热力学上不利的洞穴水的悖论.
- 提供了对疏水效应的见解和分析水在多种系统分子识别中的作用的框架.
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