Böhm H J
BASF AG, Central Research, Ludwigshafen, Germany.
J Comput Aided Mol Des. 1992 Feb;6(1):61-78. doi: 10.1007/BF00124387.
A new computer program is described, which positions small molecules into clefts of protein structures (e.g. an active site of an enzyme) in such a way that hydrogen bonds can be formed with the enzyme and hydrophobic pockets are filled with hydrophobic groups. The program works in three steps. First it calculates interaction sites, which are discrete positions in space suitable to form hydrogen bonds or to fill a hydrophobic pocket. The interaction sites are derived from distributions of nonbonded contacts generated by a search through the Cambridge Structural Database. An alternative route to generate the interaction sites is the use of rules. The second step is the fit of molecular fragments onto the interaction sites. Currently we use a library of 600 fragments for the fitting. The final step in the present program is the connection of some or all of the fitted fragments to a single molecule. This is done by bridge fragments. Applications are presented for the crystal packing of benzoic acid and the enzymes dihydrofolate reductase and trypsin.
本文描述了一种新的计算机程序，该程序可将小分子定位到蛋白质结构的裂隙中（如酶的活性位点），使得小分子能够与酶形成氢键，并且疏水口袋被疏水基团填充。该程序分三步运行。首先，它计算相互作用位点，这些位点是空间中适合形成氢键或填充疏水口袋的离散位置。相互作用位点源自通过搜索剑桥结构数据库生成的非键接触分布。生成相互作用位点的另一种途径是使用规则。第二步是将分子片段拟合到相互作用位点上。目前我们使用一个包含600个片段的库进行拟合。本程序的最后一步是将部分或全部拟合片段连接成单个分子。这通过桥连片段来完成。文中展示了该程序在苯甲酸晶体堆积以及二氢叶酸还原酶和胰蛋白酶等酶方面的应用。
