Department of Bioengineering and Therapeutic Sciences, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94158-9001, USA.
Proteins. 2011 Sep;79(9):2746-63. doi: 10.1002/prot.23103. Epub 2011 Jul 18.
Protein similarity comparisons may be made on a local or global basis and may consider sequence information or differing levels of structural information. We present a local three-dimensional method that compares protein binding site surfaces in full atomic detail. The approach is based on the morphological similarity method which has been widely applied for global comparison of small molecules. We apply the method to all-by-all comparisons two sets of human protein kinases, a very diverse set of ATP-bound proteins from multiple species, and three heterogeneous benchmark protein binding site data sets. Cases of disagreement between sequence-based similarity and binding site similarity yield informative examples. Where sequence similarity is very low, high pocket similarity can reliably identify important binding motifs. Where sequence similarity is very high, significant differences in pocket similarity are related to ligand binding specificity and similarity. Local protein binding pocket similarity provides qualitatively complementary information to other approaches, and it can yield quantitative information in support of functional annotation.
蛋白质相似性比较可以基于局部或全局进行，并且可以考虑序列信息或不同程度的结构信息。我们提出了一种局部三维方法，可详细比较蛋白质结合位点的表面。该方法基于形态相似性方法，该方法已广泛应用于小分子的全局比较。我们将该方法应用于两组人类蛋白激酶、一组来自多种物种的与 ATP 结合的非常多样化的蛋白质，以及三个异构的基准蛋白结合位点数据集。序列相似性和结合位点相似性之间的不一致情况提供了有启发性的示例。在序列相似性非常低的情况下，口袋相似性高可以可靠地识别重要的结合基序。在序列相似性非常高的情况下，口袋相似性的显著差异与配体结合特异性和相似性有关。局部蛋白质结合口袋相似性为其他方法提供了定性互补的信息，并且可以提供支持功能注释的定量信息。
