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使用原子表面位相互作用点预测蛋白质 - 连接物结合的亲和关系

Katarzyna J Zator¹, Maria Chiara Storer¹, Christopher A Hunter¹

¹Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB21EW, U.K.

Journal of chemical information and modeling

|January 14, 2026

概括

原子表面站点交互点 (AIP) 现在可以预测蛋白质-连接体结合的自由能量. 这种方法通过分析分子间相互作用和溶解效应来准确计算结合亲和力.

科学领域:

计算化学是一种计算化学.
结构生物学是结构生物学.
药物发现药物发现

背景情况:

原子表面站点交互点 (AIP) 已经成功预测了合成系统中的结合常量.
将AIP扩展到蛋白质 - 配体相互作用需要新的描述器生成和匹配技术.

研究的目的:

适应和验证原子表面位交互点 (AIP) 方法,用于预测蛋白质 - 连接体结合的自由能量.
评估基于AIP的免费能源计算与实验数据的准确性.

主要方法:

用预先计算的描述符和基于图的基结构匹配生成了蛋白质结合位点AIP.
带AIPs是从通过密度函数理论计算的分子静电电位表面衍生出来的.
通过将连接体和蛋白质AIP投射到X射线晶体结构上,确定了分子间AIP接触.

主要成果:

该方法成功地根据AIPs的空间接近性确定了分子间相互作用.
结合的总体自由能量是通过AIP接触和溶解贡献的总和来计算的.
在CASF数据集中对94个未充电的连接体复合体的应用产生了0.76的皮尔森相关系数和11kJmol-1.1的RMSD.

结论:

扩展的AIP方法提供了一种可靠的方法来预测蛋白质 - 配体结合的自由能量.
这种计算策略有望加速药物发现和开发.
准确预测结合的自由能量对于理解分子识别事件至关重要.

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