Smellie A S, Crippen G M, Richards W G
BioCAD Corporation, Mountain View, California 94043.
J Chem Inf Comput Sci. 1991 Aug;31(3):386-92. doi: 10.1021/ci00003a004.
The searching and characterization of large chemical databases has recently provoked much interest, particularly with respect to the question of whether any of the compounds in the database could serve as new leads to a compound of pharmacological interest. This paper introduces a fast and novel method of determining whether any of a given series of compounds are able, on geometrical grounds, to interact with an active site of interest. The C program written to implement the method is able to make a qualitative prediction for a given compound in about 1 s per structure (for drug-sized molecules), while still permitting the compound complete conformational freedom. However, the algorithm is sufficiently flexible to permit distance constraints to be placed on the molecules while docking. The test system studied was a family of Baker's triazines docking into the active site of dihydrofolate reductase (DHFR), as defined by a methotrexate/NADPH complex.
近期，对大型化学数据库的搜索与特性分析引发了广泛关注，尤其是关于数据库中的化合物是否能够成为具有药理学研究价值的新型先导化合物这一问题。本文介绍了一种快速且新颖的方法，用于判断给定系列化合物中的任何一种在几何层面上是否能够与目标活性位点相互作用。为实现该方法所编写的C程序，能够在大约每秒一个结构（针对药物大小的分子）的速度下，对给定化合物做出定性预测，同时仍允许化合物具有完全的构象自由度。然而，该算法具有足够的灵活性，能够在对接时对分子施加距离限制。所研究的测试系统是一族贝克三嗪对接至二氢叶酸还原酶（DHFR）的活性位点，该活性位点由甲氨蝶呤/NADPH复合物定义。
