On Protein Folding in Crowded Conditions

The interior of a cell is a highly packed environment that can be occupied up to 40% by different macromolecules. Such crowded media influence different biochemical processes like protein folding, enzymatic activity, and gene regulation. In this work, we use simulations to study protein stability under the presence of crowding agents that interact with the protein by excluded volume interactions. In general, the presence of crowding agents in the solution enhances the stability of the protein's native state. However, we find that the effects of excluded volume depend not only on crowding occupancy but also the crowders' geometry and size. Specifically, we find that polymeric crowders have stronger influence than spherical crowders and that this effect increases with polymer length, while it decreases with increasing size of spherical crowders. These opposing size effects are explained by the interplay of decreasing excluded volume and demixing, which together determine the change in the entropy of the crowders upon folding of the protein.