Quantitative Modeling of Protein-DNA Binding Specificity

与特定DNA序列结合的调节蛋白控制着许多基因的初始表达。本研究的长期目标是利用生物化学实验和计算模型相结合的方法，研究调节蛋白对特定DNA识别的规则。最初，本项目将重点建立C2H2锌指蛋白家族的完整、无偏模型。C2H2结构域是许多真核生物转录因子的共同结构域。为了开发模型，将通过这个项目收集数据。此外，将开发计算工具来分析已发表的酵母、蠕虫、苍蝇和人类的基因组，以确定C2H2家族成员的潜在靶基因。一些酵母预测将进一步分析与生化方法，以评估该方法的成功。最后，通过尝试对其他蛋白质家族进行建模，将进一步探索该方法作为一般建模方法的潜力。成功计算和比较其他蛋白质家族的模型有可能揭示家族间的相似性和差异性。通过这种方式，我们可以了解支配蛋白质- dna识别的一般规律。

Regulatory proteins, which bind to specific DNA sequences, control the initial expression of many genes. The long-term goal of this research is to investigate the rules that govern specific DNA recognition by regulatory proteins, using a combination of biochemical experimentation and computational modeling. Initially, this project will focus on building a complete, unbiased model for the C2H2 zinc finger protein family. The C2H2 domain is common to many eukaryotic transcription factors. In order to develop the model, data will be collected through this project. Furthermore, computational tools will be developed to analyze the published genomes of yeast, worm, fly and human, in order to identify potential target genes of the members of the C2H2 family. A number of yeast predictions will be analyzed further with biochemical methods in order to assess the success of the method. Finally, the potential of this method as a general modeling method will be explored further, by attempting to model other protein families. Successful calculation and comparison of models for other protein families has the potential to reveal interfamily similarities and differences. An insight on the general rules that govern the protein-DNA recognition can be gained this way.