Project Details
Projekt
Application of Methods from Information Theory in Protein Interaction Analysis
Applicants
Professor Dr. Andreas Burkovski, Ph.D.; Professor Dr.-Ing. Johannes Huber; Professor Dr. Heinrich Sticht
Subject Area
Electronic Semiconductors, Components and Circuits, Integrated Systems, Sensor Technology, Theoretical Electrical Engineering
Term
from 2010 to 2014
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 149137223
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.
DFG Programme
Priority Programmes
