酶-配体复合物亲和性的计算  

Estimating Binding Affinities for Enzyme-Ligand Complexes

作　　者：王任小[1] 李维忠[1] 来鲁华[1] 唐有祺[1] 

机构地区：[1]北京大学物理化学研究所,北京100871

出　　处：《物理化学学报》1998年第9期826-832,共7页Acta Physico-Chimica Sinica

基　　金："九五"攀登项目

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，计算结果比技准确，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。A new method is presented to estimate the binding affinity for a given enzyme-ligand complex of known three-dimensional structure This method SXORE,uses empirical scoring func-tion 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 66crystalline complexeswas analyzed by regressional statistics to obtamed the final model The model satisfactorily repro-duced the dissociation constants of the tranining set with a standard deviation of 0.86log 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.

关 键 词：药物设计 酶 配体 复合物 亲和性 定量构效关系 

分 类 号：R914.5[医药卫生—药物化学]