Intrinsically disordered protein’s coil-to-globule transition and adsorption onto a hydrophobic surface under different conditions

Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) can modulate cellular responses to environmental conditions by undergoing coil-to-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 model incorporating water’s effects on the system’s free energy to investigate how an IDP responds to a hydrophobic surface under different conditions. We show that a slit pore confinement without top-down symmetry enhances the unfolding and adsorption of the IDP 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 IDPs and IDRs can sense and adjust to external stimuli such as nanointerfaces or stresses.