Intrinsically disordered proteins (IDPs) are characterized by lack of stable tertiary structure under physiological conditions in vitro. More recently, it has been shown that ~30% of all proteins in eukaryotic organisms belong to this group and that IDPs are involved in a large number of central biological processes and diseases. This discovery challenges the traditional protein structure paradigm, which states that a specific well-defined structure is required for the correct function of a protein. Biochemical evidence has since shown that IDPs are functional, and that the lack of folded structures is related to their functions.
There is a great interest in the research community to understand the structure-function relationship for IDPs. One hypothesis states that adsorption to surfaces induces a structural rearrangement of IDPs, which gives rise to a functional state. Hence, for that purpose it is of interest to relate the properties of IDPs in solution with their properties in the adsorbed state, as well as their interaction with biological membranes. Moreover, it is of great relevance to study possible conformational changes of IDPs in the presence of solid surfaces or lipid bilayer membranes due to two reasons: (1) little is known on the effect of solid surfaced and bilayer membranes on the structure and dynamics of IDPs; and (2) most importantly, understanding how interaction with surfaces or membranes affect structure and dynamics might shed light on the fundamental biological question of how IDPs perform their biological function.
The aim of the project is to reveal static and dynamic properties of intrinsically disordered proteins (IDPs) to provide a deeper understanding of the mechanism of action and the static as well as dynamic structure-function relationship. Such knowledge is lacking today and mapping intrinsically disordered proteins will allow us to predict a structural and dynamic footprint based on amino acid composition. For this purpose we would like to establish a quantitative link between polymer theory, computer simulations, and experiments, predominantly scattering, for IDPs, as well as pushing the boundaries regarding analyzing scattering data with computer simulations.