RESUMO
The "lock-and-key" model that emphasizes the concept of chemical-structural complementary is the key mechanism for explaining the selectivity between small ligands and a larger adsorbent molecule. In this work, concerning the copolymer chain using only the combination of N-isopropylacrylamide (NIPAm) and hydrophobic N-tert-butylacrylamide (TBAm) monomers and by large-scale atomistic molecular dynamics simulations, our results show that the flexible copolymer chain may exhibit strong binding affinity for the biomarker protein epithelial cell adhesion molecule, in the absence of hydrophobic matching and strong structural complementarity. This surprising binding behavior, which cannot be anticipated by the "lock-and-key" model, can be attributed to the preferential interactions established by the copolymer with the protein's hydrophilic exterior. We observe that increasing the fraction of incorporated TBAm monomers leads to a prevalence of interactions with asparagine and glutamine amino acids due to the emerging hydrogen bonding with both NIPAm and TBAm monomers. Our findings suggest the appearance of highly specific and high-affinity binding sites on the protein created by engineering the copolymer composition, which motivates the applications of copolymers as protein affinity reagents.
