Crowding Effects Can be Quantified By Polymer Scaling Laws of Disordered Proteins

Macromolecular crowding can have a significant effect on the physical and functional properties of biological molecules. However, the experimentally observed extent of this effect varies significantly among polymeric molecules, such as unfolded proteins and intrinsically disordered proteins (IDPs). We use a simplified coarse-grained protein model to determine the effects of crowding on IDPs of varying chain properties. We find that the effect of crowding is dependent on not only crowder size and packing fraction, but also the intrinsic characteristics of the protein chain. While chains close to both the excluded volume and globule limits are far less impacted by crowding, those of intermediate polymeric characteristics experience significant compaction in crowded environments. We also propose a simple theoretical model that can capture the observed simulation trends quantitatively. Most importantly, our results help resolve current controversy surrounding the impact of crowding on disordered proteins.