Controlling the folding and substrate-binding of proteins using polymer brushes

Area of Science:

• Biophysics
• Computational Biology
• Polymer Physics

Background:

• Protein folding and substrate binding are crucial biological processes.
• The degree of coupling between folding and binding varies significantly across proteins.
• Some proteins are natively disordered and fold upon substrate interaction.

Purpose of the Study:

• To investigate the impact of disordered polymer chains on protein folding and binding dynamics.
• To understand how localized crowding affects protein-substrate interactions.
• To explore the relationship between polymer length and binding free energy.

Main Methods:

• Monte Carlo simulations were employed.
• Three model proteins with varying folding-binding coupling were studied.
• Disordered polymer chains were grafted around a model binding site.

Main Results:

• Fully folded proteins experienced greater hindrance in binding compared to those with coupled folding-binding.
• Polymer chains acted as crowding agents, promoting specific binding over non-specific adsorption.
• The free energy of contact formation showed a non-monotonic dependence on polymer length.

Conclusions:

• Disordered polymers can modulate protein binding affinity and specificity.
• The effect of polymers is dependent on the protein's intrinsic folding-binding characteristics.
• Polymer length is a critical parameter influencing the thermodynamics of protein-substrate association.