Assessing self-association of intrinsically disordered proteins by coarse-grained simulations and SAXS

This research investigates the behavior of intrinsically disordered proteins (IDPs) in solution, especially the self-associating saliva protein Statherin, by a combined computational and experimental approach. For the computational part, a bead necklace model previously parameterised for Histatin 5 was used. This model was shown to be applicable to a range of monomeric intrinsically disordered proteins and regions where the intra-chain interactions are dominated by electrostatic interactions. At high ionic strength the radius of gyration of the proteins
fit nicely to the exponential law for polymers, with an exponent of 0.59 indicating self-avoiding random walk behaviour. For the longer proteins in this study (³ 73 amino acids) a significant response to changes in the ionic strength was shown, depending on the charge distribution in the protein.
Statherin was characterised experimentally by small angle X-ray scattering and circular dichroism spectroscopy. With an additional short-ranged interaction to mimic the effect of hydrophobic interaction, the model was shown to capture the experimental trends in self-association, in regard to temperature, ionic strength and protein concentration. The combined experimental and computational approach allowed for an assessment of the intermolecular interactions contributing to the self-association. The decrease in self-association with increased temperature is considered to be an effect of mainly entropic origin, while the hydrophobic interaction was shown to be the main driving force for the self-association.