物理化学学报 >> 1998, Vol. 14 >> Issue (09): 826-832.doi: 10.3866/PKU.WHXB19980912

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酶-配体复合物亲和性的计算

王任小, 李维忠, 来鲁华, 唐有祺   

  1. 北京大学物理化学研究所，北京 100871
  • 收稿日期:1997-12-24 修回日期:1998-04-20 发布日期:1998-09-15
  • 通讯作者: 王任小

Estimating Binding Affinities for Enzyme-Ligand Complexes

Wang Ren-Xiao, Li Wei-Zhong, Lai Lu-Hua, Tang You-Qi   

  1. Institute of Physical Chemistry,Peking University,Beijing 100871
  • Received:1997-12-24 Revised:1998-04-20 Published:1998-09-15
  • Contact: Wang Ren-Xiao

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摘要：

描述了一种新的计算酶－配体复合物亲和性的方法．它考虑了酶－配体结合过程中自由能变化的各主要因素，并利用经验公式加以计算. 从蛋白质结构数据库中选取了66个酶－配体复合物作为训练集，利用回归分析得出最后的模型．此模型通用于各种类型的酶－配体复合物，计算结果比较准确，预测算合物解离常数的平均偏差小于一个数量级．此方法还可以定量评价配体分子中每个部分对结合过程的贡献大小，可以为先导他合物的优化提供非常直接的信息.

关键词: 药物设计, 酶-配体复合物, 亲和性, 基于结构的定量构效关系

Abstract:

A new method is presented to estimate the binding affinity for a given enzyme-ligand complex of known three-dimensional structure. This method, SCORE, uses empirical scoring function to describe the free energy of the binding process, which mainly accounts for enzyme-ligand interaction desolvation, and deformation effect A diverse training set of 66 crystalline complexes was analyzed by regressional statistics to obtained the final model. The model satisfactorily reproduced the dissociation constants of the tranining set with a standard deviation of 0.86 log units. A major innovation of this method is the introduction of atomic binding score This makes it a valuable tool for structure-based quantitative structure-activity relationship studies.

Key words: Drug design, Enzyme-ligand complex, Binding affinity, Structure-bsed quantitative structure-activity relationship