Parasuram Ramya, Lee Joslynn S, Yin Pengcheng, Somarowthu Srinivas, Ondrechen Mary Jo
Department of Chemistry & Chemical Biology, Northeastern University, Boston, MA 02115, USA.
J Bioinform Comput Biol. 2010 Dec;8 Suppl 1:1-15. doi: 10.1142/s0219720010005166.
A new approach to the functional classification of protein 3D structures is described with application to some examples from structural genomics. This approach is based on functional site prediction with THEMATICS and POOL. THEMATICS employs calculated electrostatic potentials of the query structure. POOL is a machine learning method that utilizes THEMATICS features and has been shown to predict accurate, precise, highly localized interaction sites. Extension to the functional classification of structural genomics proteins is now described. Predicted functionally important residues are structurally aligned with those of proteins with previously characterized biochemical functions. A 3D structure match at the predicted local functional site then serves as a more reliable predictor of biochemical function than an overall structure match. Annotation is confirmed for a structural genomics protein with the ribulose phosphate binding barrel (RPBB) fold. A putative glucoamylase from Bacteroides fragilis (PDB ID 3eu8) is shown to be in fact probably not a glucoamylase. Finally a structural genomics protein from Streptomyces coelicolor annotated as an enoyl-CoA hydratase (PDB ID 3g64) is shown to be misannotated. Its predicted active site does not match the well-characterized enoyl-CoA hydratases of similar structure but rather bears closer resemblance to those of a dehalogenase with similar fold.
本文描述了一种蛋白质三维结构功能分类的新方法，并将其应用于结构基因组学的一些实例。该方法基于利用THEMATICS和POOL进行功能位点预测。THEMATICS采用查询结构的计算静电势。POOL是一种利用THEMATICS特征的机器学习方法，已被证明能够预测准确、精确且高度局部化的相互作用位点。现在描述对结构基因组学蛋白质功能分类的扩展。将预测的功能重要残基与具有先前已表征生化功能的蛋白质的残基进行结构比对。在预测的局部功能位点的三维结构匹配，比整体结构匹配更能可靠地预测生化功能。对具有磷酸核糖结合桶（RPBB）折叠的结构基因组学蛋白质的注释得到了证实。来自脆弱拟杆菌的一种假定的葡糖淀粉酶（PDB ID 3eu8）实际上可能不是葡糖淀粉酶。最后，来自天蓝色链霉菌的一个注释为烯酰辅酶A水合酶的结构基因组学蛋白质（PDB ID 3g64）被证明注释错误。其预测的活性位点与结构相似的已充分表征的烯酰辅酶A水合酶不匹配，而是与具有相似折叠的脱卤酶的活性位点更相似。
