Oshiro C M, Kuntz I D, Dixon J S
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446, USA.
J Comput Aided Mol Des. 1995 Apr;9(2):113-30. doi: 10.1007/BF00124402.
Two computational techniques have been developed to explore the orientational and conformational space of a flexible ligand within an enzyme. Both methods use the Genetic Algorithm (GA) to generate conformationally flexible ligands in conjunction with algorithms from the DOCK suite of programs to characterize the receptor site. The methods are applied to three enzyme-ligand complexes: dihydrofolate reductase-methotrexate, thymidylate synthase-phenolpthalein and HIV protease-thioketal haloperidol. Conformations and orientations close to the crystallographically determined structures are obtained, as well as alternative structures with low energy. The potential for the GA method to screen a database of compounds is also examined. A collection of ligands is evaluated simultaneously, rather than docking the ligands individually into the enzyme.
已经开发了两种计算技术来探索酶中柔性配体的取向和构象空间。两种方法都使用遗传算法（GA）结合DOCK程序套件中的算法来生成构象灵活的配体，以表征受体位点。这些方法应用于三种酶-配体复合物：二氢叶酸还原酶-甲氨蝶呤、胸苷酸合成酶-酚酞和HIV蛋白酶-硫代缩酮氟哌啶醇。获得了与晶体学确定结构相近的构象和取向，以及低能量的替代结构。还研究了GA方法筛选化合物数据库的潜力。同时评估一组配体，而不是将配体逐个对接至酶中。
