MOLECULAR MODELLING AND DRUG DESIGN BY COMPUTER

计算机辅助分子建模技术已得到应用 药物化学实验室中的各种问题。 药效团检测和分析是一项标准任务，分析也是如此 受体位置和新先导化合物的发现已知 药效团。 模型研究：大量化合物的分子模型 NCI数据库已与X射线结构和 找出不同之处并使之合理化。 蛋白激酶C：具有正确的药效团和 其中可以激活蛋白激酶C的物质还在不断被发现。一些人 已经确定了特别强大的佛波尔竞争对手。建模 蛋白激酶C的锌指区域的结构 开始了。 酪氨酸蛋白激酶：一组结构要求 酪氨酸蛋白激酶的抑制作用已被描述并用于 搜索3D数据库以确定几种新的先导化合物。 逆转录酶抑制剂：一大系列含氟化合物 双脱氧核苷已经被模型化，并且一些结构 RT抑制的要求已经确定。 三维数据库：NCI数据库从二维到三维的转换 3-D坐标现在非常先进。一种新的结构建造方案， Chem-X，已被收购和安装，并已被发现提供 结果优于使用康科德获得的结果。

The techniques of computer-assisted molecular modeling have been applied to a variety of problems in the Laboratory of Medicinal Chemistry. Pharmacophore detection and analysis is a standard task, as is analysis of receptor sites and discovery of new lead compounds having known pharmacophores. Modeling Studies: Molecular models of a large number of compounds from the NCI database have been compared to the x-ray structures and the differences identified and rationalized. Protein Kinase C: Compounds that possess the correct pharmacophore and which can activate protein kinase C continue to be discovered. Some particularly potent phorbol competitors have been identified. Modeling of the structure of the zinc finger regions of protein kinase C has begun. Tyrosine Protein Kinase: A set of structural requirements for the inhibition of tyrosine protein kinase has been delineated and used in searches of the 3D database to identify several new lead compounds. Reverse Transcriptase Inhibitors: A large series of fluorine-containing dideoxynucleosides has been modeled and some of the structural requirements for RT inhibition have been identified. Three-Dimensional Database: Conversion of the NCI database from 2-D to 3-D coordinates is now well advanced. A new structure building program, CHEM-X, has been acquired and installed and has been found to give superior results to those obtained using CONCORD.