Folding of a Square-Well Chain in a Hard-Sphere Brush

Macromolecular crowding and geometric confinement can alter the phase behavior of biomacromolecules. Here we study the folding transition of a flexible polymer chain end tethered to a hard surface within an athermal brush composed of flexible hard-sphere chains (thus we combine confinement and crowding effects). Our model polymer is a square-well-sphere chain with short-range interaction that undergoes a first-order like coil-crystal folding transition, analogous to the all-nor-none folding of many small proteins. This chain is surrounded by a set of tangent-hard-sphere chains end-tethered on a square grid and we vary the crowding effect by changing the grid spacing. We carry out Wang-Landau simulations to construct the density of states, and thus the complete thermodynamics, for this system. In the dense brush, the folding transition temperature is suppressed, although it maintains a first-order character, indicating a destabilization of the folded state. Thus, crowding near the tethering point shifts the folding equilibrium in favor of the expanded state. This effect is opposite that seen for a similar chain in either geometric confinement [1] or crowded solution conditions [2]. [1] Macromolecules 50, 6967 (2017); [2] J. Chem. Phys. 147, 166101 (2017).