Composition-Dependent Contacts of Lipases at PEGMA/SBMA Brush Interfaces

Abstract Enzyme performance on polymer brush supports depends on brush composition, and the optimum composition differs by enzyme. The design rules governing this specificity have been difficult to resolve due to the complexity of the enzyme’s surface chemistry. In particular, it remains unclear which enzyme residues contact the interface and how those contacts change with the chemical composition of the surface. We used atomistic molecular dynamics (MD) to simulate four lipases across a five-point composition series of poly(ethylene glycol) methacrylate (PEGMA) and zwitterionic sulfobetaine methacrylate (SBMA) brushes. From pure PEGMA to pure SBMA, median residue contacts decrease by 53–63% for all four enzymes, and the polar fraction of contacting residues is higher on pure SBMA than on pure PEGMA. At each enzyme’s experimentally optimal composition, the within-enzyme fits suggest that median contacts increase and polar fraction decreases with enzyme surface solvation free energy per area, consistent with the experimental hydrophobic intensity framework but requiring validation with additional enzymes. The composition trends keep their direction when replica 1, 2, or 3 is left out of every composition, and enzyme size and shape differ little between bound and not-bound frames. These simulations provide residue-level interfacial detail that is difficult to obtain experimentally and offer a starting point for physics-based design of polymer brush supports.