Ph.D Thesis

Ph.D StudentLevi Liora
SubjectOn-Lattice Monte-Carlo Simulation of Protein-Imprinted
Polymer Gels Using Radical Polymerization
DepartmentDepartment of Chemical Engineering
Supervisor ASSOCIATE PROF. Simcha Srebnik
Full Thesis textFull thesis text - English Version


Molecular imprinting is a technique that allows the creation of recognition sites in synthetic organic or inorganic polymers, which are formed by cross-linking in the presence of a template molecule. Removal of the templates leaves cavities that fit the template molecules in size, shape and functionality. Although this technique is effective when targeting small molecules, attempts to extend it to larger template molecules, such as proteins, have failed to show similar success Proteins are large, have a flexible structure, and have a large number of functional groups available for recognition. These characteristics make it impossible to use imprinting procedures of small molecules for protein imprinting.

We used molecular simulation techniques in order to reveal the problematic points in the polymerization process of current methods. We focus on a bulk imprinting method using radical polymerization of hydrogels, relating to experimental studies on molecular imprinting of small globular proteins. We model the protein-imprinted polymer (PIP) using lattice Monte-Carlo simulation. To simulate imprinting we place charged functional monomers, cross-linkers and a globular protein, on a 3D lattice. Complexation between protein and functional monomers takes place and is followed by polymerization modeled using a modified kinetic gelation model.

First, we investigate the properties of the gel and the structure and functionality of the imprinted pore. PIP selectivity is evaluated by comparing protein interaction energy in the imprinted gel with the energy of a random process. In the second part we focus on two gel types - PIPs and templated polymers (TPs), which are polymerized in the presence of charged and uncharged proteins respectively. We calculate the imprinting factor (IF) for various polymerization conditions and compare it for both gel types. In the third part, we calculate the separation factor (α) by measuring interaction energies of the template and competitor proteins within PIP gels. We study the effect of Φ, charge fractions, protein size, and protein charge distribution on α.

Our results show significantly higher IFs for PIPs in comparison with TP gels. Monomer concentration is found to strongly correlate with imprinting efficiency (as measured by IF and α), while other parameters such as charge concentrations, protein size and charge distribution on the protein surface, has a secondary effect on imprinting. The percolation limit of protein-sized pores is found to be a significant turning point for the effect of charge concentration within the imprinted gel on IF and α.