Analysis of cocaine receptor site ligand binding by three-dimensional Voronoi site modeling approach.
Analysis of cocaine receptor site ligand binding by three-dimensional Voronoi site modeling approach.
复制标题
通过三维 Voronoi 位点建模方法分析可卡因受体位点配体结合。
DOI：
10.1021/jm00075a012
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发表时间：
1993
影响因子：
7.3
通讯作者：
Crippen,GM
中科院分区：
文献类型：
--
作者：
Srivastava,S;Crippen,GM
Voronoi方法被用来获得可卡因类似物在可卡因受体部位结合的三维模型。该方法已用于确定受体部位结合区的几何细节和物理化学性质。由于训练集中只有8种化合物，由4个区域组成的Voronoi位点模型不仅充分解释了输入化合物的结合亲和力，而且还成功地正确预测了测试集中的另外8种化合物。可卡因托烷环3-位上的苯基取代基是与活性相关的最重要的官能团，而中等的贡献来自托烷环与结合区的疏水作用。讨论了与该方法相关的一些问题，并报告了一种新的方法来评估从我们的方法获得的模型的有效性。
The Voronoi approach has been used to obtain a three-dimensional model for the binding of the cocaine analogues at the cocaine receptor site. The method has been used todetermine the geometric details and the physicochemical properties of the binding regions in the receptor site. With only eight compounds in the training set, the Voronoi site model, consisting of four regions, not only fully explains the binding affinity of the input compounds but is alsosuccessful in correctly predicting another eight compounds of the test set. The phenyl substituent at the 3-position of the tropane ring of cocaine was found to be the most significant functionality relevant for activity, while moderate contribution results from the hydrophobic interactionsof the tropane ring with the binding regions. Some of the problems associated with the approach are discussed, and we report a new procedure for evaluating the validity of the model obtained from our approach.