Intrinsically disordered proteins or IDPs are abundant in eukaryotic proteomes and they feature prominently as controllers of transcriptional regulation and cell signaling. As autonomous units IDPs fail to fold into well-defined three-dimensional structures. This raises questions regarding the origins of functional specificity of IDPs. Through innovations in molecular simulations combined with novel experiments and adaptations of polymer physics theories we have uncovered a coherent set of rules that enable the delineation of IDP sequences into distinct conformational classes. Further, we are using de novo sequence design to uncover the connections between sequence-to-conformation relationships and IDP functions. These efforts are helping us identify the physical principles that underlie rapid changes to IDP sequences despite considerable conservation of amino acid compositions. Our work highlights the role played by key polymer physics concepts in understanding sequence encoded IDP form and function.
Connecting form to function with intrinsically disordered proteins
Washington University St. Louis
Thursday, April 2, 2015
Schiciano B | 4:30pm