Quantitative Modeling of Protein-DNA Binding Specificity

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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.