Obiettivo
A major challenge in post genome biology is the functional assignment of gene products. An important goal is the identification and characterization of DNA binding proteins – especially transcription factors – and of their specific target sequences. Recent strategies for determining protein-DNA binding specificities combine experimental high throughput data with bioinformatics algorithms providing encouraging results. Structure based approaches are particularly promising, as they can predict previously undetected binding sites and open the road to the rational design of novel regulatory molecules. This project aims at expanding our current knowledge of protein-DNA binding modes. We will use structural bioinformatics methods for predicting the structure and specificity of DNA binding proteins, focusing in particular on natively unfolded protein regions (flexible segments that do not assume a fixed conformation in the native state, but become ordered upon binding) which are frequently observed in DNA binding proteins. We will first develop a general method for predicting the atomic coordinates of the DNA bound conformation of these proteins combining fragment based methods for protein structure prediction and novel DNA-protein specific energy potentials. Predicted complexes will be subsequently used to predict DNA binding sites in genomes and the accuracy assessed on the basis of available experimental reference data. The results of this project will improve our understanding of the molecular details of protein-DNA interactions, assist the annotation of genomes, and prioritize experiments aimed at verifying the predicted specificities. On a more general level, this research will further advance knowledge in the field of macromolecular interactions, a central problem in systems biology.
Campo scientifico
Parole chiave
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-IEF-2008
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
WC1E 6BT LONDON