Quantum Chemical Mass Spectrometry: Verification and Extension of the Mobile Proton Model for Histidine

Cautereels, Julie; Blockhuys, Frank

doi:10.1007/s13361-017-1636-9

Cited by 17 publications

(17 citation statements)

References 68 publications

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“…As the cleavage of the histidine amide bond leads to the formation of the b 2 ‐ion and requires a proton transfer from the initial protonation site to this amide bond, all the protonated species involved in this step should be considered. The most energy‐favorable protonation site of QHS, that is, the initial protonation site, is the imidazole ring of the histidine side chain 40 : protonation at the histidine amide oxygen atom is 47.01 kJ mol −1 less favorable, whereas protonation at the histidine amide nitrogen atom is 71.84 kJ mol −1 higher in energy (Figure 1). These energetics are consistent with the literature values and clearly show that, for QHS, amide oxygen protonation is energetically favored over amide nitrogen protonation 32 …”

Section: Resultsmentioning

confidence: 99%

“…We intended to contribute to this field of research in a similar way, but the aim was to scrutinize the important effects of side‐chain reactive functions in the presence of the imidazole moiety in the formation of b 2 ‐ions 40 . We intentionally chose more complex tripeptides corresponding to X‐His‐Ser sequences, X = Asn, Asp, Gln, Glu, His, Pro, Lys, Ser, Trp, and Tyr, to evaluate the influence of ISC interactions.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the 10 selected N‐terminal residues exhibit different organic functionalities such as carboxylic acid, amide, imidazole, primary amine, hydroxyl, indole, and phenol groups. We provided computational verification for the 10 X‐His‐Ser tripeptides using QCMS 2 : the results showed that the energetics of the three steps in the proposed mechanism allow for a competition with non‐MPM fragmentation paths, generally in favor of the MPM route 40 …”

Section: Introductionmentioning

confidence: 99%

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Quantum chemical mass spectrometry: Ab initio study of b₂‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide

Cautereels

Giribaldi

Enjalbal

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale: Both amide bond protonation triggering peptide fragmentations and the controversial b 2 -ion structures have been subjects of intense research. The involvement of histidine (H), with its imidazole side chain that induces specific dissociation patterns involving inter-side-chain (ISC) interactions, in b 2 -ion formation was investigated, focusing on the QHS model tripeptide. Methods:To identify the effect of histidine on fragmentations issued from ISC interactions, QHS was selected for a comprehensive analysis of the pathways leading to the three possible b 2 -ion structures, using quantum chemical calculations performed at the DFT/B3LYP/6-311+G* level of theory. Electrospray ionization ion trap mass spectrometry allowed the recording of MS 2 and MS 3 tandem mass spectra, whereas the Quantum Chemical Mass Spectrometry for Materials Science (QCMS 2 ) method was used to predict fragmentation patterns. Results:Whereas it is very difficult to differentiate among protonated oxazolone, diketopiperazine, or lactam b 2 -ions using MS 2 and MS 3 mass spectra, the calculations indicated that the QH b 2 -ion (detected at m/z 266) is probably a mixture of the lactam and oxazolone structures formed after amide nitrogen protonation, making the formation of diketopiperazine less likely as it requires an additional step for its formation. Conclusions:In contrast to glycine-histidine-containing b 2 -ions, known to be issued from the backbone-imidazole cyclization, we found that interactions between the side chains were not obvious to perceive, neither from a thermodynamics nor from a fragmentation perspective, emphasizing the importance of the whole sequence on the dissociation behavior usually demonstrated from simple glycine-containing tripeptides.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantum chemical mass spectrometry: Ab initio study of b₂‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide

Cautereels

Giribaldi

Enjalbal

et al. 2020

Rapid Comm Mass Spectrometry

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“…From these energies, they try to predict not only the fragmentation pathways but also intensities. However, they showed that the estimation of intensities is in general difficult, as these also depend on specific measurement conditions (figure 8 in Cautereels et al) . Janesko et al also apply quantum chemical methods to simulate and understand mass spectra.…”

Section: Introductionmentioning

confidence: 99%

“…However, they showed that the estimation of intensities is in general difficult, as these also depend on specific measurement conditions (figure 8 in Cautereels et al 17 ). 18 Janesko et al 19 also apply quantum chemical methods to simulate and understand mass spectra. However, they do not aim to simulate an entire spectrum.…”

Section: Introductionmentioning

confidence: 99%

ChemFrag: Chemically meaningful annotation of fragment ion mass spectra

et al. 2018

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Identification and structural determination of small molecules by mass spectrometry is an important step in chemistry and biochemistry. However, the chemically realistic annotation of a fragment ion spectrum can be a difficult challenge. We developed ChemFrag, for the detection of fragmentation pathways and the annotation of fragment ions with chemically reasonable structures. ChemFrag combines a quantum chemical with a rule‐based approach. For different doping substances as test instances, ChemFrag correctly annotates fragment ions. In most cases, the predicted fragments are chemically more realistic than those from purely combinatorial approaches, or approaches based on machine learning. The annotation generated by ChemFrag often coincides with spectra that have been manually annotated by experts. This is a major advance in peak annotation and allows a more precise automatic interpretation of mass spectra.

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Origin and Prediction of Highly Specific Bond Cleavage Sites in the Thermal Activation of Intact Protein Ions

Wang

Leeming

et al. 2018

Chemistry A European J

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Predicting the fragmentation patterns of proteins would be beneficial for the reliable identification of intact proteins by mass spectrometry. However, the ability to accurately make such predictions remains elusive. An approach to predict the specific cleavage sites in whole proteins resulting from collision‐induced dissociation by use of an improved electrostatic model for calculating the proton configurations of highly‐charged protein ions is reported. Using ubiquitin, cytochrome c, lysozyme and β‐lactoglobulin as prototypical proteins, this approach can be used to predict the fragmentation patterns of intact proteins. For sufficiently highly charged proteins, specific cleavages occur near the first low‐basicity amino acid residues that are protonated with increasing charge state. Hybrid QM/QM′ (QM=quantum mechanics) and molecular dynamics (MD) simulations and energy‐resolved collision‐induced dissociation measurements indicated that the barrier to the specific dissociation of the protonated amide backbone bond is significantly lower than competitive charge remote fragmentation. Unlike highly charged peptides, the protons at low‐basicity sites in highly charged protein ions can be confined to a limited sequence of low‐basicity amino acid residues by electrostatic repulsion, which results in highly specific fragmentation near the site of protonation. This research suggests that the optimal charge states to form specific sequence ions of intact proteins in higher abundances than the use of less specific ion dissociation methods can be predicted a priori.

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Quantum Chemical Mass Spectrometry: Verification and Extension of the Mobile Proton Model for Histidine

Cited by 17 publications

References 68 publications

Quantum chemical mass spectrometry: Ab initio study of b₂‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide

Quantum chemical mass spectrometry: Ab initio study of b₂‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide

ChemFrag: Chemically meaningful annotation of fragment ion mass spectra

Origin and Prediction of Highly Specific Bond Cleavage Sites in the Thermal Activation of Intact Protein Ions

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Quantum Chemical Mass Spectrometry: Verification and Extension of the Mobile Proton Model for Histidine

Cited by 17 publications

References 68 publications

Quantum chemical mass spectrometry: Ab initio study of b2‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide

Quantum chemical mass spectrometry: Ab initio study of b2‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide

ChemFrag: Chemically meaningful annotation of fragment ion mass spectra

Origin and Prediction of Highly Specific Bond Cleavage Sites in the Thermal Activation of Intact Protein Ions

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Product

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Quantum chemical mass spectrometry: Ab initio study of b₂‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide

Quantum chemical mass spectrometry: Ab initio study of b₂‐ion formation mechanisms for the singly protonated Gln‐His‐Ser tripeptide