Evaluating Models of Varying Complexity of Crowded Intrinsically Disordered Protein Solutions Against SAXS

Intrinsically disordered proteins (IDPs) adopt heterogeneous conformational ensembles in solution. The properties of the conformational ensemble are dependent upon the solution conditions, including the presence of ions, temperature and crowding, and often directly impact biological function. Many in vitro investigations focus on the properties of IDPs under dilute conditions, rather than the crowded environment found in vivo. Due to their heterogeneous nature the study of IDPs under crowded conditions is challenging both experimentally and computationally. Despite this such studies are worth pursuing due to the insight gained into biologically relevant phenomena. Here, we study the highly charged IDP Histatin 5 under self-crowded conditions in low and high salt conditions. A combination of small-angle X-ray scattering and different simulation models, spanning a range of computational complexity and detail, are used. Most models are found to have limited application when compared to results from experimen...