A theoretical investigation of the mechanism of formation of a simplified analog of the green fluorescent protein (GFP) from a peptide model

Trujillo, Cristina; Sánchez‐Sanz, Goar; Alkorta, Ibón; Elguero, José

doi:10.1007/s11224-012-0134-8

Cited by 5 publications

(4 citation statements)

References 56 publications

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“…However, after the analysis of these results, and taking into account that 1,3-H sigmatropic shifts play a main role in the mechanistic paths found, we estimated that the transformations under study could be promoted by traces of water present in the reaction mixtures. The precedents of participation of water as “proton switch” in the hydrolysis of N -arylureas to give the corresponding isocyanate and amine derivatives also encouraged us to consider this hipothesis. , Besides, several computational studies have demonstrated the beneficial effect of considering one water molecule in related hydrogen shifts. − …”

Section: Results and Discusionmentioning

confidence: 99%

Exploring the Conversion of Macrocyclic 2,2′-Biaryl Bis(thioureas) into Cyclic Monothioureas: An Experimental and Computational Investigation

et al. 2018

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Macrocyclic bis(thioureas) derived from 2,2′-biphenyl and binaphthyl skeletons have been synthesized by reaction of 2,2′-diaminobiaryl and 2,2′-bis(isothiocyanato)biaryl derivatives. The splitting of these bis(thioureas) into two units of the respective cyclic monothioureas has been monitored by NMR, shedding some light on the factors that control these processes. Additionally, a computational study revealed up to three mechanistic paths for the conversion of the 2,2′-biphenyl-derived bis(thiourea) into the corresponding monothiourea. The proposed mechanisms account for the participation of a molecule of water as an efficient proton-switch as well as for different classes of putative intermediates. The computational study also supports the ability of the thiourea group to participate in a plethora of processes, such as prototropic equilibria, sigmatropic shifts, heteroene and retro-heteroene reactions, and cis ⇆ trans isomerizations.

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Section: Results and Discusionmentioning

confidence: 99%

Exploring the Conversion of Macrocyclic 2,2′-Biaryl Bis(thioureas) into Cyclic Monothioureas: An Experimental and Computational Investigation

et al. 2018

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“…The reaction pathway connecting a dipeptide to an imidazolinone as a model for the formation of green fluorescent protein was studied by Trujillo et al [119] using DFT. High energy barriers associated with the cyclization were significantly reduced (by 4-5 kJ mol -1 ) within the water-assisted processes.…”

Section: Issuementioning

confidence: 99%

Interplay of thermochemistry and structural chemistry, the journal (volume 24, 2013, issues 3–4) and the discipline

et al. 2014

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The contents of issues 3 and 4 for the calendar year 2013 are summarized in the current review of the journal Structural Chemistry. A brief thermochemical commentary is added to the summary of each paper. Abbreviations AIM Atoms in molecules BNNT Boron nitride nanotube CNC Carbon nanocone CSD Crystal structure determination DFT Density functional theory DNB 1,5-Dinitrobiuret EDA Energy decomposition analysis HF Hartree-Fock GED Gas electron diffraction GIAO Gauge-independent atomic orbital HOMA Harmonic oscillator measure of aromaticity MD Molecular dynamics MP Møller-Plesset perturbation MP2Second-order Møller-Plesset perturbation NRT Natural resonance theory ONIOM Our own N-layered integrated molecular orbital and molecular mechanics QTAIM Quantum theory of atoms-in-molecules NAO Natural atomic orbital NBO Natural bond orbital PES Potential energy surface

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“…In 2013, Alkorta et al studied this concerted mechanism of cyclization using a simple model. 24 The energy barriers corresponding to the cyclization are 63.5 kcal/mol, but the addition of a water molecule between Gly67 amide nitrogen and Ser65 carbonyl oxygen to assist the proton transfer dramatically lowers the energy barriers by 21.1 kcal/mol. In our paper, however, 23 the results of 10 ns MD showed that there is no water between Gly67 amide nitrogen and Ser65 carbonyl oxygen to assist the proton transfer.…”

Section: Introductionmentioning

confidence: 99%

“…The MD results show that the distance between the amide nitrogen atom of Gly67 and the carbonyl carbon of Ser65 is much less than the sum of their van der Waals radii, indicating that the cyclization process is completed by the amide nitrogen atom of Gly67 attacking the carbonyl carbon of Ser65 directly, which means that the proton on the Gly67 amide nitrogen transferring to Ser65 carbonyl oxygen, and the Gly67 amide nitrogen attacking the Ser65 carbonyl carbon, is a concerted process (Figure a). In 2013, Alkorta et al studied this concerted mechanism of cyclization using a simple model . The energy barriers corresponding to the cyclization are 63.5 kcal/mol, but the addition of a water molecule between Gly67 amide nitrogen and Ser65 carbonyl oxygen to assist the proton transfer dramatically lowers the energy barriers by 21.1 kcal/mol.…”

Section: Introductionmentioning

confidence: 99%

New Insights on the Mechanism of Cyclization in Chromophore Maturation of Wild-Type Green Fluorescence Protein: A Computational Study

Zhang

Sun

et al. 2016

J. Phys. Chem. B

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Cyclization is the first step in the chromophore maturation process of the green fluorescent protein (GFP). In our previous paper [J. Phys. Chem. B 2012, 116, 1426-1436], the results of molecular dynamics simulation suggested the possibility that the amide nitrogen atom of Gly67 attacks the carbonyl carbon of Ser65 directly to complete the cyclization process (one-step mechanism). In this paper, density functional theory (DFT) and quantum mechanical/molecular mechanical (QM/MM) calculations were undertaken to study this step reaction in detail. Three cluster model systems (model A, model B, and model C) and large protein system were set up to investigate the cyclization process. Our results indicate that the one-step mechanism only exists in the two minimum models. However, in model C and the large protein system, the cyclization mechanism involves two steps: the first step is proton of Gly67 amide nitrogen transferring to carbonyl oxygen of Ser65, generating protonated amide, which is stabilized by a hydrogen bond interaction with a crystallographic water molecule, and the second step is Gly67 amide nitrogen attacking the carbonyl carbon of Ser65. Arg96 plays an important role in promoting the cyclization. The energy of cyclized product relative to reactant is about 10.0 kcal/mol endothermic, which is in line with the experimental results.

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A theoretical investigation of the mechanism of formation of a simplified analog of the green fluorescent protein (GFP) from a peptide model

Cited by 5 publications

References 56 publications

Exploring the Conversion of Macrocyclic 2,2′-Biaryl Bis(thioureas) into Cyclic Monothioureas: An Experimental and Computational Investigation

Exploring the Conversion of Macrocyclic 2,2′-Biaryl Bis(thioureas) into Cyclic Monothioureas: An Experimental and Computational Investigation

Interplay of thermochemistry and structural chemistry, the journal (volume 24, 2013, issues 3–4) and the discipline

New Insights on the Mechanism of Cyclization in Chromophore Maturation of Wild-Type Green Fluorescence Protein: A Computational Study

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