Danziger D J, Dean P M
Department of Pharmacology, University of Cambridge, U.K.
Proc R Soc Lond B Biol Sci. 1989 Mar 22;236(1283):101-13. doi: 10.1098/rspb.1989.0015.
This is the first of four papers that begin to explore the possibility of automated site-directed drug design. A general outline is given of the logical steps involved in approaching the problem. The starting point is the process of knowledge acquisition about the site. An algorithm is described here for the construction of a map of hydrogen-bonding regions at protein surfaces directly from the Brookhaven Protein Data Bank coordinates. Hydrogen-bonding atoms are located, intramolecular bonds are searched for, hydrogen-bonding atoms at the surface are found and hydrogen-bonding regions are computed at the accessible surface. A grid is placed within each region discovered and the probability of hydrogen bonding at each grid point is computed. The output of the program is a map of hydrogen-bonding regions displayed within a user-defined window. This information can be used as part of a knowledge base for the automatic construction of novel ligands to fit specified binding sites.
这是开始探索自动化定点药物设计可能性的四篇论文中的第一篇。文中给出了处理该问题所涉及逻辑步骤的总体概述。起点是关于靶点的知识获取过程。本文描述了一种算法，可直接从布鲁克海文蛋白质数据库坐标构建蛋白质表面氢键区域图谱。确定氢键原子，搜索分子内键，找到表面的氢键原子，并在可及表面计算氢键区域。在每个发现的区域内放置一个网格，并计算每个网格点处氢键形成的概率。该程序的输出是在用户定义窗口内显示的氢键区域图谱。此信息可作为知识库的一部分，用于自动构建适合特定结合位点的新型配体。
