Ghose A K, Crippen G M
J Med Chem. 1984 Jul;27(7):901-14. doi: 10.1021/jm00373a016.
A common three-dimensional receptor model has been formulated for six different classes of rat liver dihydrofolate reductase inhibits using the distance geometry approach. Altogether, 62 molecules of five different classes were used to generate the receptor model, which has 11 attractive site points and 5 repulsive ones. It gave a fit having a correlation coefficient of 0.949 and root mean square (rms) deviation of 0.527. The attractive site points of the model closely correspond to the one we reported earlier. The model successfully predicted the biological data of 33 molecules of 5 different classes, one molecule of which was a member of a new class not included in the original data set. Guidelines are put forth for the synthesis of improved inhibitors.
已使用距离几何方法为六类不同的大鼠肝脏二氢叶酸还原酶抑制剂建立了一个通用的三维受体模型。总共使用了五类不同的62个分子来生成该受体模型，该模型有11个吸引位点和5个排斥位点。所得拟合的相关系数为0.949，均方根（rms）偏差为0.527。该模型的吸引位点与我们之前报道的位点密切对应。该模型成功预测了五类不同的33个分子的生物学数据，其中一个分子属于原始数据集中未包含的新类别。还提出了合成改进抑制剂的指导原则。
