Grootenhuis P D, Karplus M
Department of Computational Medicinal Chemistry, N.V. Organon, Oss, The Netherlands.
J Comput Aided Mol Des. 1996 Feb;10(1):1-10. doi: 10.1007/BF00124460.
The Multiple Copy Simultaneous Search methodology has been used to construct functionality maps for an extended region of human thrombin, including the active site. This method allows the determination of energetically favorable positions and orientations for functional groups defined by the user on the three-dimensional surface of a protein. The positions of 10 functional group sites are compared with those of corresponding groups of four thrombin-inhibitor complexes. Many, but not all features, of known thrombin inhibitors are reproduced by the method. The results indicate that certain aspects of the binding modes of these inhibitors are not optimal. In addition, suggestions are made for improving binding by interaction with functional group sites on the thrombin surface that are not used by the thrombin inhibitors.
多拷贝同时搜索方法已被用于构建人凝血酶扩展区域（包括活性位点）的功能图谱。该方法能够确定用户定义的官能团在蛋白质三维表面上的能量有利位置和取向。将10个官能团位点的位置与四种凝血酶 - 抑制剂复合物相应基团的位置进行比较。该方法再现了已知凝血酶抑制剂的许多（但不是全部）特征。结果表明这些抑制剂结合模式的某些方面并非最佳。此外，还提出了通过与凝血酶表面上未被凝血酶抑制剂利用的官能团位点相互作用来改善结合的建议。
