Chakrabarti Saikat, Panchenko Anna R
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
BMC Bioinformatics. 2009 Jul 2;10:207. doi: 10.1186/1471-2105-10-207.
It is extremely important and challenging to identify the sites that are responsible for functional specification or diversification in protein families. In this study, a rigorous comparative benchmarking protocol was employed to provide a reliable evaluation of methods which predict the specificity determining sites. Subsequently, three best performing methods were applied to identify new potential specificity determining sites through ensemble approach and common agreement of their prediction results.
It was shown that the analysis of structural characteristics of predicted specificity determining sites might provide the means to validate their prediction accuracy. For example, we found that for smaller distances it holds true that the more reliable the prediction method is, the closer predicted specificity determining sites are to each other and to the ligand.
We observed certain similarities of structural features between predicted and actual subsites which might point to their functional relevance. We speculate that majority of the identified potential specificity determining sites might be indirectly involved in specific interactions and could be ideal target for mutagenesis experiments.
识别蛋白质家族中负责功能特异性或多样化的位点极其重要且具有挑战性。在本研究中，采用了严格的比较基准测试方案，以对预测特异性决定位点的方法进行可靠评估。随后，应用三种表现最佳的方法，通过集成方法和其预测结果的共同一致性来识别新的潜在特异性决定位点。
结果表明，对预测的特异性决定位点的结构特征进行分析可能为验证其预测准确性提供手段。例如，我们发现对于较小的距离，预测方法越可靠，预测的特异性决定位点彼此之间以及与配体的距离就越近，这一点是成立的。
我们观察到预测的亚位点与实际亚位点之间在结构特征上存在某些相似性，这可能表明它们在功能上的相关性。我们推测，大多数已识别的潜在特异性决定位点可能间接参与特定相互作用，并且可能是诱变实验的理想靶点。
