Application of Methods from Information Theory in Protein Interaction Analysis

信息论方法在蛋白质相互作用分析中的应用

• 批准号: 149137223
• 负责人: Professor Dr. Andreas Burkovski, Ph.D.
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/149137223?language=en
• 关键词: Application; Methods; Information; Theory; Protein

Our work of the first two funding periods within this priority programme has demonstrated that the concepts from information theory can be adapted to treat the biological problem of protein-protein recognition. For that purpose, we have developed a formalism based on the concept of mutual information (MI) that allows quantifying the information content of different structural features of protein interfaces. Proteins, however, do not only interact with other proteins but do also bind nucleic acids (DNA, RNA). Therefore, we want to adapt and test our MI-based approach to investigate the specificity of protein-DNA recognition in the next funding period. We will exemplarily study the regulatory proteins AmtR and CcpA as model systems, which play a crucial role in bacterial nitrogen and carbon control, but for which DNA binding specificity is yet poorly understood.In particular, we want to answer the following questions:Which sequence features are informative in protein-DNA recognition? Can we define structural features that enhance the mutual information for specific protein-DNA recognition? Do energetically strong interactions also exhibit the highest mutual information for binding?Is the majority of the information for specific binding coded by direct protein-DNA contacts (direct readout) or implicitly coded in the conformational properties of the DNA (indirect readout)? Are similar structural features responsible for the DNA binding specificity of AmtR and CcpA? Can we use the MI as a suitable measure for the design of an optimal DNA sequence that is recognized with high binding affinity? Are the principles of recognition deduced for AmtR and CcpA also transferrable to other protein-DNA complexes? Achieving these goals requires the generation of a large dataset of DNA sequences, the adaptation of our MI-based approach to DNA sequences, the identification of suitable structural features for information-theoretic analysis, and the design of novel DNA sequences.

我们在这一优先方案的前两个资助期的工作表明，信息论的概念可以适用于处理蛋白质-蛋白质识别的生物学问题。为了这个目的，我们已经开发了一个形式主义的概念的基础上的互信息（MI），允许量化的信息内容的不同结构特征的蛋白质接口。然而，蛋白质不仅与其他蛋白质相互作用，而且还结合核酸（DNA，RNA）。因此，我们希望在下一个资助期内调整和测试我们基于MI的方法，以研究蛋白质-DNA识别的特异性。我们将以调节蛋白AmtR和CcpA为模型系统进行研究，这两种蛋白在细菌氮和碳控制中起着至关重要的作用，但对它们的DNA结合特异性还知之甚少。特别是，我们想回答以下问题：哪些序列特征在蛋白质-DNA识别中提供信息？我们能否定义出增强特定蛋白质-DNA识别互信息的结构特征？能量强的相互作用是否也表现出最高的结合互信息？特异性结合的大部分信息是由蛋白质-DNA直接接触编码的（直接读出）还是隐含在DNA的构象特性中编码的（间接读出）？AmtR和CcpA的DNA结合特异性是否由相似的结构特征决定？我们是否可以使用MI作为设计具有高结合亲和力的最佳DNA序列的合适措施？AmtR和CcpA的识别原理是否也适用于其他蛋白质-DNA复合物？实现这些目标需要产生一个大的数据集的DNA序列，我们的MI为基础的方法适应DNA序列，识别合适的结构特征的信息理论分析，和设计新的DNA序列。