药效假说在配体从头设计中的适用性探讨

DISCUSSIONS ABOUT APPLICABILITY OF PHARMACOPHORE HYPOTHESISIN DE NOVE DESIGN OF LIGANDS

在基于靶蛋白结构的多肽分子设计中，药效假说是从头设计方法的基本前提。虽然该假说是否成立已有不少议论，但尚未见到系统分析的报道。通过对８ 个蛋白质复合物界面做了氨基酸模拟图谱，并从模拟图谱的结构偏差与能量分量的关系，对药效假说的适用条件进行了讨论。同时也给出一个ＨＩＶ－ １ 蛋白酶及抑制剂复合物的功能图谱。从所得结果来看，药效假说在以氨基酸为药效基团时，尽管不少情况下仍然有效，但不是普遍成立的。

Pharmacophore hypothesis(PH) is fundamental to de novo design of peptide ligand based on the structure of target protein. Though it was often discussed, it has not been systematically verified. With the simulated mapping of amino acids at interface of eight protein complexes, and the relationship between structure deviation and energy components, the conditions on application of pharmacophore hypothesis have been discussed: the pharmacophore hypothesis can come into existence in many cases, but there are still more or less counterexamples.