Computational approaches in the design of synthetic receptors – A review

Cowen, Todd; Karim, Kal; Piletsky, Sergey A.

doi:10.1016/j.aca.2016.07.027

Cited by 146 publications

(97 citation statements)

References 130 publications

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“…In contrast, molecular imprinting is a method relying on synthetic chemistry and self-assembly. The tools for selection of functional monomers include an array of molecular modelling techniques that be used to greatly improve the likelihood of successful imprinting through a process of in silico design21. In addition, the formation of imprinted nanoparticles by solid phase synthesis is a rapid method that produces soluble particles bearing surface accessible binding sites and is capable of automation234.…”

Section: Resultsmentioning

confidence: 99%

A comparison of the performance of molecularly imprinted polymer nanoparticles for small molecule targets and antibodies in the ELISA format

Smolińska-Kempisty

Guerreiro

Canfarotta

et al. 2016

Sci Rep

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100

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Here we show that molecularly imprinted polymer nanoparticles, prepared in aqueous media by solid phase synthesis with immobilised L-thyroxine, glucosamine, fumonisin B2 or biotin as template, can demonstrate comparable or better performance to commercially produced antibodies in enzyme-linked competitive assays. Imprinted nanoparticles-based assays showed detection limits in the pM range and polymer-coated microplates are stable to storage at room temperature for at least 1 month. No response to analyte was detected in control experiments with nanoparticles imprinted with an unrelated template (trypsin) but prepared with the same polymer composition. The ease of preparation, high affinity of solid-phase synthesised imprinted nanoparticles and the lack of requirement for cold chain logistics make them an attractive alternative to traditional antibodies for use in immunoassays.

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Section: Resultsmentioning

confidence: 99%

A comparison of the performance of molecularly imprinted polymer nanoparticles for small molecule targets and antibodies in the ELISA format

Smolińska-Kempisty

Guerreiro

Canfarotta

et al. 2016

Sci Rep

Self Cite

100

View full text Add to dashboard Cite

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“…22 The reason for this lies in small variations in the structure and a large number of polar domains in a large protein that cannot be discriminated by virtually designed polymers in molecular modelling experiments. 23 Unfortunately it is very difficult to model hydrophobic interactions, which otherwise would be useful for the design of MIPs for an aqueous environment. In addition, the requirement to perform imprinting in an aqueous environment limits the number of monomers available for polymerisation.…”

Section: Introductionmentioning

confidence: 99%

New protocol for optimisation of polymer composition for imprinting of peptides and proteins

Bedwell

Anjum

et al. 2019

RSC Adv.

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We present here a novel screening tool for optimisation of polymerisation mixtures used in imprinting of peptides and proteins. To facilitate rapid synthesis and screening of a combinatorial library of polymers the solid-phase synthesis method developed by Piletsky and co-workers was scaled down to 50 mg of template-immobilised solid phase, allowing a single well of a 96-well microplate to function as an individual reaction vessel. In this way, 32 different polymer compositions containing Nisopropylacrylamide, acrylic acid, N-(3-aminopropyl)methacrylamide hydrochloride, and N-tertbutylacrylamide, were tested in imprinting of three peptides and three proteins. Utilising filtration microplates has allowed the elution and washing steps to be performed in a similar manner to the largescale synthesis, whilst incorporation of a fluorescent monomer (N-fluoresceinylacrylamide) made it possible to analyse the binding of synthesised polymer nanoparticles to the solid phase with immobilised templates under different washing conditions. The experiment has proven that the variations in monomer compositions had an effect on the yield and affinity of synthesised molecularly imprinted polymers for the peptides, but not for the proteins. Imprinting in this way presents an ideal method for performing small-scale syntheses for testing polymerisation mixtures, as information regarding the molecularly imprinted polymers affinity can be assessed as part of the elution process, without a need for time-consuming analysis such as quartz crystal microbalance or surface plasmon resonance.

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“…Different computational approaches including molecular mechanics, molecular dynamics, 29 quantum chemical calculation (QCC), 30 and molecular docking (MD) were successfully used for a rational design of MIPs through the prediction, simulation, and estimation of molecular interactions between a template molecule and a monomer in a prepolymerization complex as well as in a polymer matrix. [31][32][33] Thus, Piletsky's group created a virtual library of functional monomers, which could be screened by a molecular modeling software against a template molecule of interest aiming at preselecting a group of preferential monomers for the following generation of more selective MIPs. 34,35 Dong et al calculated energy of H-bond interactions in simulated complexes between a template and a monomer using a QCC (density functional theory).…”

Section: Introductionmentioning

confidence: 99%

A computational approach to study functional monomer-protein molecular interactions to optimize protein molecular imprinting

et al. 2017

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Molecular imprinting has become a promising approach for synthesis of polymeric materials having binding sites with a predetermined selectivity for a given analyte, the so-called molecularly imprinted polymers (MIPs), which can be used as artificial receptors in various application fields. Realization of binding sites in a MIP involves the formation of prepolymerization complexes between a template molecule and monomers, their subsequent polymerization, and the removal of the template. It is believed that the strength of the monomer-template interactions in the prepolymerization mixture influences directly on the quality of the binding sites in a MIP and consequently on its performance. In this study, a computational approach allowing the rational selection of an appropriate monomer for building a MIP capable of selectively rebinding macromolecular analytes has been developed. Molecular docking combined with quantum chemical calculations was used for modeling and comparing molecular interactions among a model macromolecular template, immunoglobulin G (IgG), and 1 of 3 electropolymerizable functional monomers: m-phenylenediamine (mPD), dopamine, and 3,4-ethylenedioxythiophene, as well as to predict the probable arrangement of multiple monomers around the protein. It was revealed that mPD was arranged more uniformly around IgG participating in multiple H-bond interactions with its polar residues and, therefore, could be considered as more advantageous for synthesis of a MIP for IgG recognition (IgG-MIP). These theoretical predictions were verified by the experimental results and found to be in good agreement showing higher binding affinity of the mPD-based IgG-MIP toward IgG as compared with the IgG-MIPs generated from the other 2 monomers.

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Computational approaches in the design of synthetic receptors – A review

Cited by 146 publications

References 130 publications

A comparison of the performance of molecularly imprinted polymer nanoparticles for small molecule targets and antibodies in the ELISA format

A comparison of the performance of molecularly imprinted polymer nanoparticles for small molecule targets and antibodies in the ELISA format

New protocol for optimisation of polymer composition for imprinting of peptides and proteins

A computational approach to study functional monomer-protein molecular interactions to optimize protein molecular imprinting

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