Comparison of descriptors for predicting selectivity of protein‐imprinted polymers

Abstract

Molecular imprinting is a technique that is used to create artificial receptors by the formation of a polymer network around a template molecule, creating a molecularly imprinted polymer. These artificial receptors may be used in applications that require molecular recognition, such as enantioseparations, biosensors, artificial catalysis, drug delivery and others. Small molecules, such as drugs, have been imprinted with high efficiency and, combined with the low cost of preparation, molecularly imprinted polymers have acquired commercial usage. While attempts at imprinting proteins have been significantly less successful, the great potential of protein-imprinted polymers (PIPs) in medicine and industry attracted much research. Multifunctionality, conformational flexibility, large size of the proteins, and aqueous polymerization environment are some of the obstacles faced by protein imprinting. We explore the relation between PIP selectivity and the properties of the template and competitor proteins. A comprehensive statistical analysis of published studies reveals a statistically significant correlation between four protein descriptors and the corresponding selectivity of PIPs. Namely, a PIP will generally be more selective against large competitor proteins with a smooth surface, whose isoelectric point and aspect ratio are significantly different than those of the template protein. The size of the protein, as measured by its molecular weight, appears to be independent of the template protein characteristics. Copyright © 2016 John Wiley & Sons, Ltd.

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

“…Imprinting of molecules of biological relevance sparked particular interest as such synthetic materials can potentially substitute expensive immunoassays. However, efforts to generate imprints of proteins have in general shown limited specificity and relatively high affinity towards competitor proteins . The difficulties encountered with protein imprinting can be attributed to several factors, such as the use of water as solvent, which diminishes the long‐range selective interactions, the presence of multiple weak interactions on the surface of proteins, the relatively flexible conformation of the macromolecule, and the large molecular size of the protein.…”

“…Building on the idea of incorporation of a number of functional groups to the polymer matrix, various methods have been developed to improve the performance of PIPs, though the most extensive experimental work on PIPs has focused on 3‐dimensional imprinting using polyacrylamide gels due to their biocompetability, neutrality, and relative ease of processing . However, these efforts have so far resulted in relatively minor improvement of PIP performance …”

“…Further statistical analysis on published studies suggested that protein characteristics play a large role in the selectivity of the PIP. That is, PIPs will generally be more selective against large competitor proteins with a smooth surface, whose isoelectric point and aspect ratio are significantly different than those of the template protein . In this work, we continue our analysis using a lattice model that involves 4 types of functional monomers (hydrophobic (H), polar (P), positively charged, and negatively charged) and include a soft potential to allow diffusion of the protein within the gel.…”

“…However, efforts to generate imprints of proteins have in general shown limited specificity and relatively high affinity towards competitor proteins. [7][8][9] The difficulties encountered with protein imprinting can be attributed to several factors, such as the use of water as solvent, which diminishes the long-range selective interactions, the presence of multiple weak interactions on the surface of proteins, the relatively flexible conformation of the macromolecule, and the large molecular size of the protein. Furthermore, the overall surface chemistry (average number of residue types) of globular proteins is only marginally different from 1 protein to another.…”

“…14 However, these efforts have so far resulted in relatively minor improvement of PIP performance. 8,9 Several computational approaches to study molecularly imprinted polymers have been introduced during the past decade. As recently reviewed, 7 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.…”