Gas-Phase Conformation of Biological Molecules:  Bradykinin

Wyttenbach, Thomas; Helden, Gert von; Bowers, Michael T.

doi:10.1021/ja9535928

Cited by 380 publications

(393 citation statements)

References 53 publications

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“…The significance of this result is discussed subsequently. Previous studies have shown that ion cross sections for a particular type of structure do depend on energy, but these effects are typically observed over a much wider energy range (i.e., 20-60 kcal/mol) than the very small 3-kcal/mol range investigated here [37,38,45,47]. The range of the cross sections in those studies over a small (e.g., 3 kcal/mol) range obscures any weak trend with energy as is the case in this study.…”

Section: Calculated Cross Sectionscontrasting

confidence: 51%

“…Both AMBER* [28,37,38,45,48,49] and CHARMm [33,35,52] have been extensively used to obtain low-energy structures for comparison with ion mobility data. Structures calculated by using MMFF were also included in this study because evaluations of different force fields by others suggest that this force field can provide accurate results when compared with experimental data [70] or higher levels of theory [71].…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

“…Higher level calculations are often done on low-energy structures identified at the mechanics level. Ion mobility has been used to characterize a wide range of ion structures including carbon clusters [25][26][27], amino acids [28,29], peptides [30][31][32][33][34][35][36][37], proteins [39][40][41][42][43], DNA [44][45][46][47], and synthetic polymers [48][49][50]. Bowers and coworkers showed that the cross sections of gas-phase valinomycin-alkali ion complexes are the same for lithiated and sodiated species, but steadily increase for potassiated, rubidiated, and cesiated complexes [51].…”

mentioning

confidence: 99%

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Evaluation of ion mobility spectroscopy for determining charge-solvated versus salt-bridge structures of protonated trimers

Wong

Williams

Counterman

et al. 2005

J. Am. Soc. Mass Spectrom.

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The cross sections of five different protonated trimers consisting of two base molecules and trifluoroacetic acid were measured by using ion mobility spectrometry. The gas-phase basicities of these five base molecules span an 8-kcal/mol range. These cross sections are compared with those determined from candidate low-energy salt-bridge and charge-solvated structures identified by using molecular mechanics calculations using three different force fields: AMBER*, MMFF, and CHARMm. With AMBER*, the charge-solvated structures are all globular and the salt-bridge structures are all linear, whereas with CHARMm, these two forms of the protonated trimers can adopt either shape. Globular structures have smaller cross sections than linear structures. Conclusions about the structure of these protonated trimers are highly dependent on the force field used to generate low-energy candidate structures. With AMBER*, all of the trimers are consistent with salt-bridge structures, whereas with MMFF the measured cross sections are more consistent with charge-solvated structures, although the assignments are ambiguous for two of the protonated trimers. Conclusions based on structures generated by using CHARMm suggest a change in structure from charge-solvated to salt-bridge structures with increasing gas-phase basicity of the constituent bases, a result that is most consistent with structural conclusions based on blackbody infrared radiative dissociation experiments for these protonated trimers and theoretical calculations on the uncharged base-acid pairs. T he structure of a molecule in solution depends both on intramolecular interactions and on intermolecular interactions between the molecule and solvent. Gas-phase studies can provide information about the intrinsic properties of a molecule. From such measurements, information about solvent effects can be inferred. A number of different methods can provide information about molecular structure in the gas phase, even complex systems, such as large synthetic or biological polymers. These methods include spectroscopy [1][2][3][4][5], hydrogen/deuterium exchange [6-12], dissociation [13][14][15][16][17][18], proton transfer reactivity [19][20][21][22], and ion mobility mass spectrometry . These methods have been used to obtain information about protein conformation and folding, DNA duplex structure, and in a wide variety of other interesting applications.Of these methods, ion mobility mass spectrometry, a method pioneered by Bowers and Jarrold for ion structure characterization, has several advantages, including rapid measurement time, minimal perturbation of ground state structure, exquisite temperature control, and the ability to investigate kinetics of structural change over a limited time. With ion mobility, ions are injected into a drift tube where they thermalize through collisions with an introduced background gas, typically helium. In the presence of an applied electric field, ions are made to drift through an elevated pressure region. Based on the drift time through this tube...

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Section: Calculated Cross Sectionscontrasting

confidence: 51%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of ion mobility spectroscopy for determining charge-solvated versus salt-bridge structures of protonated trimers

Wong

Williams

Counterman

et al. 2005

J. Am. Soc. Mass Spectrom.

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“…Alternatively, the low intensity of the double adduct may be a result of the compact conformation that bradykinin preferentially adopts in the gas phase. For example, singly protonated bradykinin forms a compact salt bridge structure in the gas phase [14]. Attachment of doubly deprotonated DP to this structure would lead to an anionic complex.…”

Section: Selective Complexationmentioning

confidence: 99%

Selective molecular recognition of arginine by anionic salt bridge formation with bis-phosphate crown ethers: implications for gas phase peptide acidity from adduct dissociation

Julian

Beauchamp

2004

J. Am. Soc. Mass Spectrom.

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Arginine forms a stable noncovalent anionic salt bridge complex with DP (a crown ether which contains two endocyclic dialkylhydrogenphosphate esters). Abundant adduct formation with DP is observed for complexes with arginine, YAKR, HPPGFSPFR, AAKRKAA, RR, RPPGF-SPFR, RYLGYL, RGDS, and YGGFMRGL in electrospray ionization mass spectrometry (ESI-MS) experiments. DFT calculations predict a hydrogen bonded salt bridge structure with a protonated guanidinium flanked by two deprotonated phosphates to be the lowest energy structure. Dissociation of DP/peptide adducts reveals that, in general, the relative gas phase acidity of a peptide is dependent on peptide length, with longer peptides being more acidic. In particular, peptides that are six residues or more in length can stabilize the deprotonated C-terminus by extensive hydrogen bonding with the peptide backbone. Dissociation of DP/peptide complexes often yields the deprotonated peptide, allowing for the facile formation of anionic peptides that otherwise would be difficult to generate in high abundance. Although DP has a preference for binding to arginine residues in peptides, DP is also observed to form less abundant complexes with peptides containing multiple lysines. Lys-Xxx-Lys and Lys-Lys sequences form low abundance anionic adducts with DP. For example, KKKK exclusively forms a double adduct with one net negative charge on the complex. T he development of methods that enable the rapid identification and characterization of proteins, especially those providing information relating to sequence, structure, and function, will facilitate new discoveries in the emerging field of proteomics [1,2,3]. Toward this goal, we have undertaken the development and systematic study of reagents that will selectively bind to peptides and proteins though specific noncovalent complexation of targeted amino acids both in solution and in the gas phase. For example, electrospray ionization (ESI) experiments employing 18-crown-6 ether (18C6) to form noncovalent complexes with lysine containing peptides and proteins have yielded valuable information about sequence and structure [4]. In these experiments, attachment of 18C6 to peptides yields quantitative information about the number of lysines present, whereas complexation with proteins reveals information about the tertiary structure and surface availability of lysine residues [4]. In a related work, 18C6 serves as a molecular scaffold for the attachment of a diazo functional group, yielding a reagent known as a "molecular mousetrap" because of its ability to convert noncovalent complexes into covalently bound molecules following appropriate activation to form a reactive carbene [5].Similar recognition of the side chain of arginine has been accomplished with larger crown ethers such as dibenzo-30-crown-10, which forms extensive hydrogen bonds with the protonated alkyl-guanidinium side chain of arginine [6]. Recognition of arginine can also be accomplished through the formation of salt bridges. A variety of solution phase reagents such...

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