Structural characterization of protein-imprinted gels using lattice Monte Carlo simulation

Molecular imprinting finds relevance and importance in a range of applications including the development of new chemical sensors, separation technologies, and selective binding particularly for catalytic and bioreactors. While molecular imprinting technology has found success when imprinting small molecules, progress in molecular imprinting of biomacromolecules, such as polypeptides and proteins, is hindered, in part due to their large size and complex functionality. Unlike with small molecules, imprinting of biomacromolecules results in poor performance of the imprinted gel, characterized by significant nonspecific binding of molecules of similar shape and size to the template. Our research in this field aims to characterize the structure of proteinimprinted gels in an effort clarify the effects that lead to poor protein imprinting. The determination and study of the three dimensional molecular structure of such supramolecular assemblies is a challenging problem. To gain a general understanding of the process, we focus on simplified coarse-grained lattice models that are known to capture some generic and universal properties of polymer gels and biopolymers. The protein and imprinting matrix are modeled using coarse-grained lattice techniques, where gelation is simulated using a modified kinetic gelation algorithm. Structural and functional properties are probed using protein diffusion within the gel. Different gelation conditions are considered and analyzed for imprinting performance. The effects of protein size, hydrophobicity, charge, and flexibility on gel structure are studied. In this work, we focus on a bulk imprinting method using radical polymerization of hydrogels, in an effort to reveal the problematic points in the polymerization process, which ultimately result in low imprinting efficiency. We relate to the work of Ou et al. [1] and Kimhi et al. [2], who studied molecular imprinting of small globular proteins (lysosyme and cytochrome c) in polyacrylamide gels with electrostatic functional groups. We will present the method and results of the structural, energetic and functional properties of these imprinted gels and compare them with experimental observations. ∗ Corresponding author: [email protected]. Current address: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742