Godden J W, Stahura F, Bajorath J
Computational Chemistry and Informatics, MDS Panlabs, Bothell, Washington 98011-8805, USA.
J Mol Graph Model. 1998 Jun;16(3):139-43, 165. doi: 10.1016/s1093-3263(99)00003-0.
In an effort to establish efficient docking routines for computational screening of compound databases on protein structures, cAMP-dependent protein kinase has been selected as a test case and a variety of docking options and scoring functions were compared. These included rigid-body and flexible docking and scoring based on surface complementarity and/or force field energy. Inhibitors were removed from complex crystal structures and added to compound libraries in their binding conformations and, in addition, deliberately modified conformations. Rigid-body docking and contact scoring well reproduced two of three experimental enzyme-inhibitor complexes. Ligand docking with flexible torsional angles failed to do so but anchored search of some inhibitors converged near to experimental structures, however, only when energy scoring was applied.
为了建立用于在蛋白质结构上对化合物数据库进行计算筛选的高效对接程序，已选择环磷酸腺苷（cAMP）依赖性蛋白激酶作为测试案例，并比较了多种对接选项和评分函数。这些包括基于表面互补性和/或力场能量的刚体对接和柔性对接及评分。从复杂晶体结构中去除抑制剂，并将其以结合构象添加到化合物库中，此外，还对构象进行了刻意修饰。刚体对接和接触评分很好地重现了三个实验性酶 - 抑制剂复合物中的两个。具有柔性扭转角的配体对接未能做到这一点，但一些抑制剂的锚定搜索在实验结构附近收敛，然而，只有在应用能量评分时才会如此。
