Burkhard P, Taylor P, Walkinshaw M D
Structural Biochemistry, The University of Edinburgh, Michael Swann Building, Edinburgh, EH9 3JR, U.K.
J Mol Biol. 1998 Mar 27;277(2):449-66. doi: 10.1006/jmbi.1997.1608.
A computer program (SANDOCK) has been developed for the automated docking of small ligands to a target protein. It uses a guided matching algorithm to fit ligand atoms into the protein binding pocket. The protein is described by a modified Lee-Richard's dotted surface with each dot coded by chemical property and accessibility. Orientations of the ligand in the active site are generated such that a chemical and a shape complementary between the ligand and the active site cavity have to be fulfilled. The generated fits are evaluated with scoring functions which account for van der Waals, hydrophobic and hydrogen bonding interactions. This newly developed docking program can efficiently screen very large databases in a reasonable time and has been used to successfully identify novel ligands. The X-ray structure of a thrombin-ligand complex predicted by SANDOCK is described. The ligand binds to thrombin with a Kd of 65 microM and has an rmsd of 0.7 A for all ligand atoms from the predicted binding mode by SANDOCK.
已开发出一种计算机程序（SANDOCK），用于将小分子配体自动对接至目标蛋白。它使用一种引导匹配算法，将配体原子拟合到蛋白质结合口袋中。蛋白质由经过修改的Lee-Richard's点表面描述，每个点都由化学性质和可及性编码。生成配体在活性位点的取向，使得配体与活性位点腔之间必须满足化学和形状互补性。使用考虑范德华力、疏水作用和氢键相互作用的评分函数对生成的拟合进行评估。这个新开发的对接程序能够在合理时间内高效筛选非常大的数据库，并已成功用于识别新型配体。描述了由SANDOCK预测的凝血酶-配体复合物的X射线结构。该配体与凝血酶结合，解离常数（Kd）为65微摩尔，并且与SANDOCK预测的结合模式相比，所有配体原子的均方根偏差（rmsd）为0.7埃。
