Unstructured
proteins can modulate cellular responses
to environmental conditions by undergoing coil–globule transitions
and phase separation. However, the molecular mechanisms of these phenomena
still need to be fully understood. Here, we use Monte Carlo calculations
of a coarse-grained model incorporating water’s effects on
the system’s free energy. Following previous studies, we modeled
an unstructured protein as a polymer chain. Because we are interested
in investigating how it responds to thermodynamic changes near a hydrophobic
surface under different conditions, we chose an entirely hydrophobic
sequence to maximize the interaction with the interface. We show that
a slit pore confinement without top-down symmetry enhances the unfolding
and adsorption of the chain in both random coil and globular states.
Moreover, we demonstrate that the hydration water modulates this behavior
depending on the thermodynamic parameters. Our findings provide insights
into how homopolymers and possibly unstructured proteins can sense
and adjust to external stimuli such as nanointerfaces or stresses.