Hopfinger A J
J Med Chem. 1983 Jul;26(7):990-6. doi: 10.1021/jm00361a011.
A general formalism, based upon molecular mechanics pairwise potential functions, has been developed to compute the molecular potential energy fields inherent to a given molecule in a given conformation. Molecular descriptors are derived from the potential energy fields, which can be used in QSAR studies based upon molecular shape analysis. These descriptors have been computed for a set of 2,4-diamino-5-benzylpyrimidines that are dihydrofolate reductase (DHFR) inhibitors. A QSAR is derived in which DHFR inhibition activity can be explained in terms of molecular shape, as represented by differences in molecular potential energy fields between pairs of superimposed molecules, and the sum of the pi constants of substituents on the 3- and 4-position of the benzyl ring. This QSAR is superior to one developed earlier (Hopfinger, A. J. J. Med. Chem. 1981, 24, 818) in which molecular shape is described by common overlap steric volume. Ancillary information defining the "active" conformation and electrostatic nature of the binding site are realized in the construction of the QSAR.
基于分子力学成对势函数，已开发出一种通用形式体系，用于计算给定构象下给定分子固有的分子势能场。分子描述符源自势能场，可用于基于分子形状分析的定量构效关系（QSAR）研究。已针对一组作为二氢叶酸还原酶（DHFR）抑制剂的2,4-二氨基-5-苄基嘧啶计算了这些描述符。推导了一种QSAR，其中DHFR抑制活性可以用分子形状来解释，分子形状由叠加分子对之间分子势能场的差异表示，以及苄基环3位和4位取代基的π常数之和。这种QSAR优于早期开发的一种（霍普芬格，A.J.《药物化学杂志》1981年，24卷，818页），在早期的QSAR中，分子形状由共同重叠空间体积来描述。在QSAR的构建中实现了定义“活性”构象和结合位点静电性质的辅助信息。
