ICBS:: a database of interactions between protein chains mediated by β-sheet formation
ICBS:: a database of interactions between protein chains mediated by β-sheet formation
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DOI：
10.1093/bioinformatics/bth326
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发表时间：
2004-11-01
期刊：
影响因子：
5.8
通讯作者：
Baldi, P
中科院分区：
文献类型：
--
作者：
Dou, YM;Baisnée, PF;Baldi, P
动机：链间β折叠（Interchain beta-sheet，ICBS）相互作用广泛存在于蛋白质四级结构、蛋白质间相互作用和蛋白质聚集中。这些相互作用发挥了核心作用，在许多生物过程和疾病，从艾滋病和癌症炭疽和阿尔茨海默氏症。结果：我们已经创建了一个全面的数据库ICBS的相互作用，每周更新，并允许条目进行排序和搜索的相关性和其他标准，通过一个简单的Web界面。我们推导出一个简单的ICBS指数来量化β-梯在整体链间相互作用中的相对贡献，并计算关于β-链中不同相对位置的氨基酸组成和配对的一阶和二阶统计。对数据库的分析显示，显著的ICBS相互作用的发生率为15.8%，其中大多数涉及反平行β折叠的形成，其中许多涉及二聚体和寡聚体的形成。ICBS界面中氨基酸的频率与链内β-折叠界面中的频率相似。侧链之间的各种非共价相互作用补充了主链之间的氢键相互作用。在反平行（i，j）对中，极性氨基酸优先与极性氨基酸配对，非极性氨基酸优先与非极性氨基酸配对。我们预计，从数据库中获得的统计数据和见解将指导控制链间β-折叠相互作用的药物的开发，并且数据库将有助于确定这些药物的新蛋白质相互作用和靶点。
Motivation: Interchain beta-sheet (ICBS) interactions occur widely in protein quaternary structures, interactions between proteins and protein aggregation. These interactions play a central role in many biological processes and in diseases ranging from AIDS and cancer to anthrax and Alzheimer's.Results: We have created a comprehensive database of ICBS interactions that is updated on a weekly basis and allows entries to be sorted and searched by relevance and other criteria through a simple Web interface. We derive a simple ICBS index to quantify the relative contributions of the beta-ladders in the overall interchain interaction and compute first- and second-order statistics regarding amino acid composition and pairing at different relative positions in the beta-strands. Analysis of the database reveals a 15.8% prevalence of significant ICBS interactions, the majority of which involve the formation of antiparallel beta-sheets and many of which involve the formation of dimers and oligomers. The frequencies of amino acids in ICBS interfaces are similar to those in intrachain beta-sheet interfaces. A full range of non-covalent interactions between side chains complement the hydrogen-bonding interactions between the main chains. Polar amino acids pair preferentially with polar amino acids and non-polar amino acids pair preferentially with non-polar amino acids among antiparallel (i, j) pairs. We anticipate that the statistics and insights gained from the database will guide the development of agents that control interchain beta-sheet interactions and that the database will help identify new protein interactions and targets for these agents.