Towards Rational Design of Selective Molecularly Imprinted Polymers (MIPs) for Proteins: Computational and Experimental Studies of Acrylamide-Based Polymers for Myoglobin

Molecularly imprinted polymers (MIPs) have the potential to become alternatives to antibodies in the diagnosis and treatment of disease. However, atomistic level knowledge of the prepolymerization process is currently limited that would facilitate the rational design of more efficient MIPs. Towards this goal, we have investigated using computation and experiment the protein-monomer binding interactions that may influence the desired specificity. For this purpose, myoglobin was used as the target protein and five different acrylamide-based monomers considered. Protein binding sites were predicted using SiteMap and binding free energies of monomers at each of the sites calculated using post-docking MM-GBSA. Statistical thermodynamic analysis of binding and study of the atomistic interactions facilitated rationalization of the relative efficacy of the different monomers in MIP rebinding studies (% rebind; imprinting factors). CD spectroscopy was used to determine the effect of monomers on myoglobin secondary...