Due to their conformational malleability, intrinsically disordered proteins (IDPs) are particularly susceptible to influences of crowded cellular environments. Here we report a computational study of the effects of macromolecular crowding on the conformational ensemble of a coarse-grained IDP model, by using two approaches. In one, the IDP is simulated along with the crowders; in the other, crowder-free simulations are postprocessed to predict the conformational ensembles under crowding. We found significant decreases in the radius of gyration of the IDP under crowding, and suggest repulsive interactions with crowders as a common cause for chain compaction in a number of experimental studies. The postprocessing approach accurately reproduced the conformational ensembles of the IDP in the direct simulations here, and holds enormous potential for realistic modeling of IDPs under crowding, by permitting thorough conformation sampling for the proteins even when they and the crowders are both represented at the all-atom level.
Keywords: Intrinsically disordered proteins; macromolecular crowding; postprocessing approach.