Computer simulation based selection of optimal monomer for imprinting of tri-O-acetiladenosine in polymer matrix: vacuum calculations

Barkaline, Viatcheslav; Douhaya, Yana; Tsakalof, Andreas

doi:10.1007/s00894-012-1561-6

Cited by 9 publications

(8 citation statements)

References 10 publications

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“…When noncovalent interactions at the nanoscale have to be investigated in large systems, as in this work, Quantum Mechanics and Molecular Mechanics (QM/MM) approaches have to be applied. QM/MM methods have proven to be reliable and helpful in investigating such large systems [14][15][16]. Thus, here, building blocks were first studied at quantum level and then for larger systems (more than 100-150 atoms) a QM/MM method was adopted.…”

Section: Computational Approachesmentioning

confidence: 99%

Correlation between macroscopic sugar transfer and nanoscale interactions in cation exchange membranes

Fuoco

Galier

Balmann

et al. 2015

Journal of Membrane Science

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a b s t r a c tPrevious experimental work has shown that the transfer of organic solutes through ion-exchange membranes depends on the membrane counter-ion and that this dependence is probably linked to the interactions taking place at the nanoscale inside the membrane matrix. In this paper, a computational approach is carried out, combining quantum mechanics and molecular mechanics to determine the interactions occurring at the nanoscale, taking a cation exchange membrane as example. Building blocks are first accurately studied at high level of quantum theory, before being merged in macromolecular models. The computed interactions are then compared to the experimental values of the solute flux in order to point out the nanoscale mechanisms governing the solute transfer. The computed glucose À polymer fragment interactions, related to the sugar solubility inside the membrane, are found to be almost independent from the membrane counter ion. On the contrary, significant variations of the chain À chain interaction, i.e. the interaction energies per trapped water molecule or hydrogen bonding wire connecting the polymer fragments, were observed according to the cation. Moreover, a correlation was pointed out with the experimental sugar fluxes obtained with 3 different sugars. Increasing chain À chain interactions inside the membrane was found to give decreasing sugar flux. Then this work shows that the cohesion energy between the polymer fragments fixes the dependence of the sugar flux versus the membrane counter-ion. The crucial role of the water molecules coordinating the cations is also highlighted.

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Section: Computational Approachesmentioning

confidence: 99%

Correlation between macroscopic sugar transfer and nanoscale interactions in cation exchange membranes

Fuoco

Galier

Balmann

et al. 2015

Journal of Membrane Science

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“…This could be as a consequence of the different morphology of the polymer and lower order of pre-polymerization complexes formed in acetonitrile, with both contributing to a decrease in bindingsite-type diversity. However, the energy of MMAÀN3 binding is twice as weak as that of cooperative cyclic MAAÀ(C6ÀNH2···N1) and MAAÀ(C6ÀNH2···N7) [27] and this binding may not be preserved in acetonitrile. Indeed, a 1 H NMR spectroscopy titration of EA9A with MAA in acetonitrile [24] yielded a binding stoichiometry of 1:1.4, which was intermediate between a 1:1 and 1:2 template/monomer ratio and theoretically could be referred to as first-and second-order complexes (Figure 1 B).…”

Section: Equilibrium Rebinding Experiments and Binding Characteristicmentioning

confidence: 99%

“…The coordination of a third carboxylic acid (MAA or VBA) to N3 (Figure 1 A) gives rise to the 1:3 third-order complexes. However, the energy of MMAÀN3 binding is twice as weak as that of cooperative cyclic MAAÀ(C6ÀNH2···N1) and MAAÀ(C6ÀNH2···N7) [27] and this binding may not be preserved in acetonitrile. In acetonitrile, 1:1 and 1:2 pre-polymerization complexes are formed, yielding binding sites with low and medium affinity (first and second order in Figure 1 B), whereas in low-polarity solvents (chloroform, [28] benzene) additionally 1:3 complexes can be formed to give rise to high-affinity binding sites and simultaneously increasing the structural diversity of the binding sites and heterogeneity in template affinity.…”

Section: Equilibrium Rebinding Experiments and Binding Characteristicmentioning

confidence: 99%

Molecular Imprinting of Tri‐O‐Acetyladenosine for the Synthetic Imitation of an ATP‐Binding Cleft in Protein Kinases

Lakka

Tsakalof

2013

ChemPlusChem

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A number of diseases, including cancer, diabetes, and inflammation, are linked to deregulation of cell signaling pathways controlled by protein kinases. Inhibition of the kinases involved can interrupt aberrant signaling and have a specific therapeutic effect. Protein kinases are recognized as validated therapeutic targets for the treatment of a number of diseases and there are considerable efforts to discover new kinase inhibitors suitable for drug development. The main goal of this study was to fabricate the synthetic imitations of the adenosine triphosphate (ATP) binding cleft in protein kinases and thus produce polymers suitable for screening and isolation of new protein kinase ATP‐mimetic inhibitors from different sources. Such polymers were created by the imprinting of tri‐O‐acetyladenosine in acrylic polymer matrix with the use of methacrylic acid (MAA) or 3‐vinylbenzoic acid (VBA) as a functional monomer and ethylene glycol dimethacrylate as a cross‐linking agent. The imprints prepared with the use of VBA demonstrate substantially better binding efficiency than that with MAA and particularly high affinity to the initial template (Kd as low as 1.2 μM), sufficient concentration of binding sites N (up to 32 μmol g−1), and pronounced specificity (imprinting factor up to 11). Under flow conditions, the fabricated polymers also demonstrate high capacity and template affinity. The produced imprints reproduce spatially noncovalent interactions present in the ATP binding site of protein kinases and can be anticipated as approximate synthetic imitations of the binding cleft.

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“…Such a system was able to mimic the formation of the recognition cavities in the polymer matrix as well as its interaction with the various analytes . The hybrid quantum‐mechanical/molecular mechanical approach for a rational design of MIPs was applied by several authors . However, most of these reports describe the computational methods to model complexes of functional monomers with low molecular‐weight templates.…”

Section: Introductionmentioning

confidence: 99%

“…37 The hybrid quantum-mechanical/molecular mechanical approach for a rational design of MIPs was applied by several authors. 36,[38][39][40][41] However, most of these reports describe the computational methods to model complexes of functional monomers with low molecular-weight templates. At the same time, there are very few computational studies on macromolecular MIPs that mostly use the molecular mechanics simulations, 42 MD, 43,44 and lattice Monte Carlo simulations.…”

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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Computer simulation based selection of optimal monomer for imprinting of tri-O-acetiladenosine in polymer matrix: vacuum calculations

Cited by 9 publications

References 10 publications

Correlation between macroscopic sugar transfer and nanoscale interactions in cation exchange membranes

Correlation between macroscopic sugar transfer and nanoscale interactions in cation exchange membranes

Molecular Imprinting of Tri‐O‐Acetyladenosine for the Synthetic Imitation of an ATP‐Binding Cleft in Protein Kinases

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

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