血管紧张素II 1型受体的三维药效团模型的推导

Derivation of a 3D pharmacophore model for the angiotensin-II site one receptor.

作者信息

Prendergast K, Adams K, Greenlee W J, Nachbar R B, Patchett A A, Underwood D J

机构信息

Molecular Systems Department, Merck Research Laboratories, Rahway, NJ 07065.

出版信息

J Comput Aided Mol Des. 1994 Oct;8(5):491-512. doi: 10.1007/BF00123662.

DOI:10.1007/BF00123662

PMID:7876897

Abstract

A systematic search has been used to derive a hypothesis for the receptor-bound conformation of A-II antagonists at the AT1 receptor. The validity of the pharmacophore hypothesis has been tested using CoMFA, which included 50 diverse A-II antagonists, spanning four orders of magnitude in activity. The resulting cross-validated R2 of 0.64 (conventional R2 of 0.76) is indicative of a good predictive model of activity, and has been used to estimate potency for a variety of non-peptidyl antagonists. The structural model for the non-peptide has been compared with respect to the natural substrate, A-II, by generating peptide to non-peptide overlays.

摘要

通过系统检索得出了关于A-II拮抗剂在AT1受体上与受体结合构象的假说。使用比较分子场分析（CoMFA）对药效团假说的有效性进行了测试，该分析包括50种不同的A-II拮抗剂，其活性范围跨越四个数量级。得到的交叉验证R2为0.64（传统R2为0.76），表明该活性预测模型良好，并已用于估计多种非肽类拮抗剂的效力。通过生成肽与非肽的重叠结构，将非肽的结构模型与天然底物A-II进行了比较。