Inferring properties of intrinsically disordered proteins from single-molecule FRET and small-angle X-ray scattering data*

Intrinsically disordered proteins are a class of polypeptides in which a significant portion of the chain is not folded into a specific three-dimensional structure. Because of their abundance and importance in many biological contexts, it is important to characterize the extent of structure formation in these proteins. However, as a result of their extensive disorder, conventional structure-determination methods used for folded proteins are not appropriate, and the broad distribution of structures in such a disordered system needs to be considered. I will describe methods for using molecular simulations to account for the diversity of structures in intrinsically disordered proteins while fitting to the experimental data, which help to reconcile differences between different experimental methods. Methods based on molecular simulation are more computationally demanding, but also the most general approach. I will show how in many cases, if the IDP is sufficiently disordered, it is also possible to use simpler approximations which we have developed.