柔性多肽片段–蛋白质相互作用的全局对接方法  

Global Docking Method for Flexible Peptide Segment-Protein Interactions

作　　者：来瑞颖 万波 黄强[1] 

机构地区：[1]复旦大学生命科学学院,上海

出　　处：《计算生物学》2014年第2期42-52,共11页Hans Journal of Computational Biology

基　　金：上海市重点学科建设项目(B111)。

摘　　要：多肽–蛋白质的相互作用在生物细胞中发挥着各种各样重要的作用。通常情况下,它们之间的结合信息是未知的。所以,利用计算方法预测结合位点具有重要意义。而以Rosetta为代表的常用对接软件通常具有很强的初始位置依赖性。为克服这一局限性,本研究提出了一种全局对接的方法,以受体蛋白为球状系统的中心,将多肽平均地分布在球面26个位置上;同时定义了一个区分天然结合构象和非天然结合构象的筛选参数。用上述方法预测多肽–蛋白质的结合构象,结果显示该方法能成功预测蛋白质的结合位点,且多数多肽的预测构象的Cα-RMSD在5.5 Å以下。因此,研究结果表明,所发展的方法在蛋白质多肽结合位点预测方面有很好的应用价值。Protein-peptidebinding plays various important roles in living cells. In many cases, thepeptide- binding sites of proteins are not known in prior. Then, computationalprediction of the peptide- binding sites isdesirable. Popular programs for protein-peptide docking usually depend stronglyon the initial positions of peptides, such as Rosetta. To overcome thislimitation, here we develop a global docking approach in which the peptide isinitially distributed evenly on 26 surface locations of a virtual sphere aroundthe protein, and define a selection parameter for discriminating native-likebinding site from non-native sites. We used this approach to predict thenative-like binding conformations of peptide-protein complexes, and in mostcases the peptide-binding sites were correctly predicted, with Cα-RMSDsbelow 5.5 Åwith respect to the crystal structures of peptides. The results ofthis study suggested that our approach may be very useful for theidentification of peptide-binding sites of proteins.

关 键 词：多肽–蛋白质相互作用 多肽结合位点 分子对接 

分 类 号：R73[医药卫生—肿瘤]