Revisiting Protein-Copolymer Binding Mechanisms: Insights beyond the "Lock-and-Key" Model

Area of Science:

• Polymer Chemistry
• Biomolecular Interactions
• Computational Biophysics

Background:

• The lock-and-key model explains ligand-adsorbent selectivity based on structural complementarity.
• Understanding molecular interactions is crucial for designing targeted biomaterials.

Purpose of the Study:

• To investigate the binding affinity of N-isopropylacrylamide (NIPAm) and N-tert-butylacrylamide (TBAm) copolymers with biomarker proteins.
• To explore binding mechanisms beyond traditional structural complementarity.

Main Methods:

• Large-scale atomistic molecular dynamics simulations were employed.
• Analysis focused on copolymer-protein interactions, including hydrophobic matching and hydrogen bonding.

Main Results:

• Copolymers exhibited strong binding affinity for epithelial cell adhesion molecule, irrespective of hydrophobic matching or structural complementarity.
• Binding was attributed to preferential interactions with the protein's hydrophilic exterior.
• Increased TBAm content enhanced interactions with asparagine and glutamine via hydrogen bonding.

Conclusions:

• The lock-and-key model is insufficient to explain these observed binding behaviors.
• Copolymer composition engineering can create specific, high-affinity protein binding sites.
• These findings support the use of copolymers as novel protein affinity reagents.