Molecular Simulations of Recognitive Behavior of Molecularly Imprinted Intelligent Polymeric Networks

Henthorn, David B.; Peppas, Nicholas A.

doi:10.1021/ie061369l

Cited by 32 publications

(33 citation statements)

References 58 publications

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“…[1,16] The kinetic gelation model (KGM) describes the chemistry of irreversible polymer gelation and relates to the rules of initiation, propagation, termination and radical trapping. [25][26][27] KGMs generally describe the formation of a rigid network without relating to the flexibility of the resulting structure. Verdier et al [28,29] present a MC method for studying polymer chain dynamics and equilibrium configurations.…”

Section: Modelmentioning

confidence: 99%

Structural Characterization of Protein‐Imprinted Gels Using Lattice Monte Carlo Simulation

Levi

Srebnik

2010

Macromolecular Symposia

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Summary: Molecular imprinting is a technique for the creation of artificial recognition sites in synthetic organic or inorganic polymers, 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 has been shown to be effective when targeting small rigid molecules, attempts to extend it to larger templates, such as proteins, have failed to show similar success. As opposed to small molecules, proteins are characterized by large size, flexible structure, and large number of functional groups available for recognition. These characteristics, among others, make it impossible to use imprinting procedures of small molecules for protein imprinting. In order to plan new imprinting strategies for proteins, one must reveal the problematic points in the polymerization process of the current methods, which result in low imprinting efficiency. In our research we focus on a bulk imprinting method using radical polymerization of hydrogels, applied to small globular proteins (e.g., lysosyme and cytochrome c). We model the system using lattice Monte Carlo (MC) simulation, using a modified kinetic gelation model (KGM) to simulate the polymerization process, which results in an inflexible proteinimprinted gel. The effect of initiator molar ratio, polymer volume fraction (VF), crosslinker density, and protein charge density and distribution on gelation, gel structure, and on the imprinted pore structure and functionality is investigated in the dry state of the gel. It is found that the imprinted pores wrap the template protein more fully and with larger number of linking sites than the non-imprinted pores. The insertion of non-template proteins with various charge densities and distributions into the imprinted pores indicates that charge density of the adsorbing protein is the dominant factor influencing the number of linked recognition sites.

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Section: Modelmentioning

confidence: 99%

Structural Characterization of Protein‐Imprinted Gels Using Lattice Monte Carlo Simulation

Levi

Srebnik

2010

Macromolecular Symposia

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“…Molecular simulations are a tool that can be used for the rational design of protein MIPs by providing molecular-level understanding of functional monomers with high affinity for amino acid residues and minimal disruption of the protein structure. There has, however, been very limited work in protein MIPs with molecular simulations to date despite the success of several analogous studies in the small molecular weight MIP regime (Chianella et al 2002;Henthorn and Peppas 2007;Pavel and Lagowski 2005;Piletsky et al 2001). The addition of a large macromolecule in modeling obviously requires more computationally demanding simulations; however, the rapid advancement of high performance computing now makes such rigorous studies feasible.…”

Section: Guidelines For the Future Of Macromolecular Imprintingmentioning

confidence: 99%

Conformational studies of common protein templates in macromolecularly imprinted polymers

Kryscio

Fleming

Peppas

2012

Biomed Microdevices

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Unlike the molecular imprinting of small molecule templates, molecularly imprinted polymers specific to large templates (>1,500 Da), have achieved limited success to date. Conformational stability of these labile macromolecules is one of the main factors that prevent the direct extension of successful procedures from the small molecule regime. We continue our systematic investigation of the effect of common components in macromolecular MIPs on the conformation of protein templates. Circular dichroism was used to show that frequently employed monomers and crosslinkers induce significant changes in the secondary structures of lysozyme and bovine hemoglobin. The extent to which this change occurs, at ligand concentrations far below what are typically used reported work, is cause for concern and provides as rational explanation for the lack of success in this arena. This is because a change in the template structure prior to polymerization would lead to the binding sites formed during polymerization to be specific to this alternate conformation. Subsequent studies with the macromolecule in its native state and the crosslinked network would not be successful. Using this information as a guide, we offer suggestions as to where work in macromolecular imprinted polymers should focus going forward in order for these antibody mimics to reach their vast potential as a new class of biomedical diagnostic devices.

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“…The literature provides numerous examples where researchers have investigated the strength of monomer-template interactions through the use of molecular mechanics (MM) [3][4][5][6], molecular dynamics (MD) [7][8][9], and quantum mechanics (QM) [10,11], based molecular modelling techniques, but these are still limited by the sequential screening of each monomer manually.…”

Section: Introductionmentioning

confidence: 99%

A Protocol for the Computational Design of High Affi nity Molecularly Imprinted Polymer Synthetic Receptors

Karim¹,

Cowen²,

Guerreiro³

et al. 2017

Glob J Biotechnol Biomater Sci

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Molecularly imprinted polymer (MIP) nanoparticles, commonly referred to as 'plastic antibodies' or synthetic receptors, are polymeric materials with strong affi nity and selectivity for a particular chemical target. MIPs are regularly produced for use in sensors for monitoring food quality and environmental pollutants, and in the design of robust and affordable replacements for biological receptors, enzymes and antibodies in drug testing and assays. More recently the easy production of MIP nanoparticles has also permitted research relating to possible in vivo applications, primarily in drug delivery systems, toxin sequestration and pathogen inhibition. The strength of the interaction between the target and the polymer binding site is dependent on the particular monomers selected in synthesis of the MIP, and the relative concentrations of these in the pre-polymerization mixture. While computational approaches have been used to aid in MIP design previously, the methods adopted are often slow and simplistic, centring on observations of the template structure with a couple of functional monomers presumed to be appropriate. We present here an automated method of rapidly screening numerous functional monomers and effectively determining appropriate monomer ratios, while accounting for spatial discrimination in selection and dynamic parameters in optimization. Example are then given of effect MIP synthesis resulting from the protocol, and the benefi ts of this approach over competing methods are discussed.

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Molecular Simulations of Recognitive Behavior of Molecularly Imprinted Intelligent Polymeric Networks

Cited by 32 publications

References 58 publications

Structural Characterization of Protein‐Imprinted Gels Using Lattice Monte Carlo Simulation

Structural Characterization of Protein‐Imprinted Gels Using Lattice Monte Carlo Simulation

Conformational studies of common protein templates in macromolecularly imprinted polymers

A Protocol for the Computational Design of High Affi nity Molecularly Imprinted Polymer Synthetic Receptors

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