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When genomic medicine faces disordered proteins…
Each of the residues in a protein has unique properties. In folded proteins, a certain sequence of residues will produce a defined three dimensional structure and put these unique properties into the right place to fulfill a specific task. Hence, the predicting the outcome of mutations in structured proteins is comparatively straightforward once the protein structure has been determined.
A lot has been speculated about the function and modes of action of intrinsically disordered proteins (IDPs). Despite the lack of stringent sequence conservation, IDPs bear an in-built capability to reliably interact with many partners. Interestingly, even overlapping binding motifs can easily be accommodated. Since IDPs do not form a distinctive characteristic structure, novel approaches for their description need to be established that allow adequate parameterization of their properties.
By studying such proteins systematically in vivo by saturation mutagenesis studies, in vitro by determining their transient structure and interactions and combining it with novel in silico methods, we try to identify the common denominators of crucial interaction motifs and develop methods for understanding their role in protein-protein interaction networks.