一个多层次的模拟框架,用于阐明复杂的生物分子环境中可光开关联体的光化学结构-活性关系
Amirhossein Bakhtiiari1, Mohammad Khavani1, Gustavo J Costa1
1Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States.
Journal of chemical information and modeling
|November 20, 2025
概括
这项研究引入了一种多尺度模拟框架,以预测可光切换药物如何与蛋白质相互作用,揭示影响其光激活抗癌活性的关键因素,并指导未来药物设计.
科学领域:
- 计算化学是一种计算化学.
- 生物物理学的生物物理.
- 药理学 药理学是指药理学的学科.
背景情况:
- 由于复杂的生物分子相互作用和动态,对可光交换的配体进行光化学结构-活性关系 (光SAR) 的预测具有挑战性.
- 现有的方法难以准确地模拟蛋白质-连接体相互作用,电子相关性和合的核/电子动态.
研究的目的:
- 开发一个统一的多尺度模拟框架,以预测复杂的生物环境中的光SAR.
- 研究光定 (PST),光调节抗癌剂的光动力学和结合亲和力.
- 提供可光切换配体的合理设计的机械洞察力.
主要方法:
- 集成的第一原则非adiabatic动态,兴奋状态增强采样,和基本状态的化学自由能量计算.
- 将框架应用于光静态素 (PST),并根据实验数据 (晶体学,光谱,生物测试) 进行验证.
- 热力学集成与其他自由能量方法进行准确性比较.
主要成果:
- 非辐射衰变速率与激发状态的自由能量表面相关,受替代剂,蛋白质静电学和硬质束的影响.
- 蛋白质静电加速放松,而固体约束阻碍它,确定PST衍生光动力学.
- 光异构化量子收益率取决于扭转运动对齐和基态异构化倾向,两者都是由蛋白质-连接体相互作用形成的.
- 热力学融合最好地捕捉了替代剂对异构体之间的结合亲和力差异的影响.
结论:
- 开发的框架准确地预测了可光开关联体的光动力学和响应光的结合亲和力.
- 蛋白质静电学和固态因子批判性地调节激发状态动力学和光异构化量子产量.
- 这种方法促进了可光切换配体的合理设计,用于生物和生物医学应用.
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