THE COMPUTER-PROGRAM LUDI - A NEW METHOD FOR THE DENOVO DESIGN OF ENZYME-INHIBITORS
THE COMPUTER-PROGRAM LUDI - A NEW METHOD FOR THE DENOVO DESIGN OF ENZYME-INHIBITORS
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DOI：
10.1007/bf00124387
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发表时间：
1992-02-01
影响因子：
3.5
通讯作者：
BOHM, HJ
中科院分区：
文献类型：
--
作者：
BOHM, HJ
描述了一种新的计算机程序，该程序将小分子定位到蛋白质结构的裂缝（例如酶的活性位点）中，使得可以与酶形成氢键，并且疏水口袋填充有疏水基团。该计划分为三个步骤。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。通过搜索剑桥结构数据库，从非键合接触的分布中得到相互作用位点。生成交互站点的另一种途径是使用规则。第二步是将分子片段装配到相互作用位点上。目前，我们使用600个片段的文库进行拟合。本程序的最后一步是将部分或全部拟合片段连接到单个分子上。这是由桥梁碎片完成的。介绍了苯甲酸以及二氢叶酸还原酶和胰蛋白酶的晶体包装的应用。
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.