通过构建蛋白质结构域功能模版库做基于氨基酸序列的蛋白质功能位点预测(英文)  

Sequence-based Functional Sites Prediction from a Function Annotated Protein Domain Profile Database

作　　者：安雄博 武肖坤 明灯明[1] 

机构地区：[1]复旦大学生命科学学院生理学和生物物理学系,上海200433

出　　处：《复旦学报（自然科学版）》2013年第6期768-778,783,共12页Journal of Fudan University：Natural Science

基　　金：supported,in part,by the National Natural Science Foundation of China(NNSFC)(Grant No.30870509 and 31270759);a startup funding of Fudan University

摘　　要：由蛋白质序列预测蛋白质功能位点对于理解蛋白质功能具有重大的意义,它同时也为生物学实验提供了重要依据.长期以来,基于知识库的方法一直是预测蛋白质功能位点的可靠方法.通过适当修改蛋白质结构分类库SCOP构建了一个附带功能注释的结构域模版库(fDPD),其中每个模版都包含一组序列和结构都非常相近的已知的蛋白质成员.fDPD通过隐马尔可夫模型方法HMMER由未知蛋白质的序列预测其功能位点.为了考察本方法的效果我们检测了两个通用的酶催化位点数据库,一个由约1 500个序列构成的钙离子结合蛋白数据库和从CASP9中提取出的数条蛋白质序列.我们的方法对于配体结合位点以及钙结合位点的预测取得了较高的精度和覆盖率,其催化位点的预测效果仅次于目前已知的最好的方法.我们的计算结果表明,结构上相似的蛋白质其功能位点倾向于出现在蛋白质表面上相似的位置.Prediction of functional sites from protein sequence is a key to annotation of protein function and provides important evidence for biology experiments. For a long time the knowledge-based method has been reliable tool for protein function as well as functional site prediction. In this study, we build a function annotated protein domain profile database （fDPD） in which protein sequences that have similar known structures are condensed into a representative profile, using the Structural Classification of Proteins （SCOP） domain database, fDPD makes predictions based on the profile hidden Markov models （HMM）. We examined the method using two standard enzyme datasets, a set of ~1 500 calcium binding proteins and a list of target protein from CASP9. The method achieves significant precision-recall for ligand-binding/calcium-binding site predictions, while for catalytic site prediction it ranks the second best compared with recent published works. Our calculations indicated that similar protein structures might have their functional sites located on similar protein surface areas, despite their sequence variations, fDPD and source codes are available upon request.

关 键 词：功能位点预测 SCOP结构域 HMM FDPA fDPD 

分 类 号：Q811.4[生物学—生物工程]