There is an ongoing controversy on the coil-to-globule transition of IDPs due to disagreement between SAXS and FRET experiments, known as "SAXS-FRET discrepancy". IDPs are heteropolymers and FRET experiments suggest IDPs undergo coil-to-globule transition with dilution of denaturant concentration whereas SAXS experiments conclude water acts as a good solvent to IDPs. We provide a theory to explain the origin of such discrepancy taking inspiration from polymer physics. We tested our theory for different length of polyleucine and polyglutamine chains by varying concentration of denaturant and osmolyte, [urea] and [TMAO]. Increase (decrease) of [Urea] ([TMAO]) modulate the solvent quality from poor to good.
Expansion factor in terms of radius of gyration for (A) polymer, (B) polyleucine, and (C) polyglutamine as a function of chain length for different concentrations of denaturant (urea) and osmolyte (TMAO). Phase diagram suggests coil-globule transition exists within a region called "crossover region" instead of a point. Crossover region depends on chain length and amino acid composition of IDPs.