Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Protein J. 2013 Jun;32(5):373-85. doi: 10.1007/s10930-013-9494-1.
The similarity comparison of binding sites based on amino acid between different proteins can facilitate protein function identification. However, Binding site usually consists of several crucial amino acids which are frequently dispersed among different regions of a protein and consequently make the comparison of binding sites difficult. In this study, we introduce a new method, named as chemical and geometric similarity of binding site (CGS-BSite), to compute the ligand binding site similarity based on discrete amino acids with maximum-weight bipartite matching algorithm. The principle of computing the similarity is to find a Euclidean Transformation which makes the similar amino acids approximate to each other in a geometry space, and vice versa. CGS-BSite permits site and ligand flexibilities, provides a stable prediction performance on the flexible ligand binding sites. Binding site prediction on three test datasets with CGS-BSite method has similar performance to Patch-Surfer method but outperforms other five tested methods, reaching to 0.80, 0.71 and 0.85 based on the area under the receiver operating characteristic curve, respectively. It performs a marginally better than Patch-Surfer on the binding sites with small volume and higher hydrophobicity, and presents good robustness to the variance of the volume and hydrophobicity of ligand binding sites. Overall, our method provides an alternative approach to compute the ligand binding site similarity and predict potential special ligand binding sites from the existing ligand targets based on the target similarity.
基于不同蛋白质之间氨基酸的结合位点相似性比较可以促进蛋白质功能的鉴定。然而，结合位点通常由几个关键氨基酸组成，这些氨基酸经常分散在蛋白质的不同区域，因此使得结合位点的比较变得困难。在这项研究中，我们引入了一种新的方法，称为配体结合位点的化学和几何相似性（CGS-BSite），该方法基于离散氨基酸使用最大权二分匹配算法来计算配体结合位点的相似性。计算相似性的原理是找到一个欧几里得变换，使得在几何空间中相似的氨基酸彼此近似，反之亦然。CGS-BSite 允许结合位点和配体的灵活性，在灵活的配体结合位点上提供稳定的预测性能。使用 CGS-BSite 方法对三个测试数据集进行的结合位点预测与 Patch-Surfer 方法具有相似的性能，但优于其他五种测试方法，基于接收者操作特征曲线下的面积，分别达到 0.80、0.71 和 0.85。它在体积小、疏水性高的结合位点上的表现略优于 Patch-Surfer，并且对配体结合位点的体积和疏水性的变化具有良好的鲁棒性。总的来说，我们的方法提供了一种替代方法来计算配体结合位点的相似性，并基于目标相似性从现有配体靶标预测潜在的特殊配体结合位点。
