Simulation of Protein-Imprinted Polymers. 2. Imprinting Efficiency

Abstract

Molecular imprinting allows the creation of artificial recognition sites in synthetic materials through polymerization and cross-linking in the presence of template molecules. Removal of the templates leaves cavities that are complementary to the template molecules in size, shape, and functionality. Although this technique is effective when targeting small molecules, attempts to extend it to larger templates, such as proteins, have failed to show similar success. Here we present the second report on our model simulation study of protein imprinting, in which we apply on-lattice Monte Carlo simulations for an imprinting process using radical polymerization of hydrogels as a simple model for protein-imprinted polymers (PIPs). In this part we focus on two gel types: PIPs and templated polymers (TPs), which are polymerized in the presence of charged and neutral proteins, respectively. We calculate the imprinting factor (IF) for gels formed at various conditions and compare it for both gel types. Our results show a significantly higher IF for PIPs, and though the strongest influence on IF is found to be the monomer concentration (Φ), charge concentrations on the protein and in solution also affect IF. The percolation limit of protein-sized pores is found to be a significant turning point for the effect of concentration of functional sites within the gels on IF.

Molecular Docking Simulations for Macromolecularly Imprinted Polymers

“…They found that the presence of the protein template had no effect on the average structure of the resultant polymer and that highly charged pre-polymerization solutions led to non-specific interactions. These conclusions agree with previous independent experimental studies from Bergmann and Peppas 17 and Janiak et al 18 In their most recent work, Levi and Srebnik 15 employed the same model to determine that monomer concentration in the pre-polymerization solution had the strongest influence on imprinting efficiency.…”

A brief review of coarse‐grained and other computational studies of molecularly imprinted polymers

“…The concentration of charged monomers in solution, as well as fraction of charged surface residues on the protein, were also found to influence protein binding to the imprinted pore, decreasing linearly with increasing charge densities in the solution and on the protein. However, solution charge was also found to significantly influence the extent of recognition in the imprinted gel, with maximum selectivity obtained at relatively low charge concentrations (Levi and Srebnik, ), as was observed with experiments of PIPs (Janiak and Kofinas, ) and simulations of MIPs (Dourado and Sarkisov, ).…”

“…We evaluated the structure and functionality of the imprinted pore and calculated IFs and SFs by modeling diffusion of the protein within the imprinted pore. The interaction of the protein with the imprinted pore was most strongly influenced by the monomer concentration of the prepolymerization solution, with minimal recognition achieved below the percolation limit of protein‐sized pores in the gel (Levi and Srebnik, ). The concentration of charged monomers in solution, as well as fraction of charged surface residues on the protein, were also found to influence protein binding to the imprinted pore, decreasing linearly with increasing charge densities in the solution and on the protein.…”

The selectivity of protein‐imprinted gels and its relation to protein properties: A computer simulation study

“…During equilibration of the template protein in solution with the functional monomers, its interaction energy is expected to be optimal. Once the gel is polymerized, the optimal interaction with the monomers is hindered due to deformation of the equilibrium distribution of functional monomers around the template protein and the restricted movement of the cross‐linked monomers . Still, the interaction energy of the protein within the imprinted site of the polymer gel is O (10ε) compared with O (1ε) at other sites.…”

“…As recently reviewed, the majority of these studies tend to focus on prepolymerization complexation of the templates and functional monomers, since a correlation between properties of the prepolymerization solution and final imprinting efficiency has been shown to exist . We recently performed lattice Monte Carlo (MC) simulations of the imprinting process using radical polymerization of hydrogels as a simple model for such PIPs . For simplicity, these first studies used a rigid model protein with randomly located functional sites of only 1 type.…”