Effects of peptide chain length on the gas-phase proton transfer properties of doubly-protonated ions from bradykinin and its N-terminal fragment peptides

Pallante, Giovanni A.; Cassady, Carolyn J.

doi:10.1016/s1387-3806(02)00556-0

Cited by 18 publications

(13 citation statements)

References 69 publications

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“…, all of the possible charge configurations compatible with a given charge state) of these biomolecules is performed coupling force field–based molecular dynamics and density functional theory (DFT) calculations. In contrast to previous computational studies [25] , [31] , [52] , [62] , [63] , [79] , [80] , all of the charge states generated by ionized and/or neutral basic (R, K, H, Q, N-terminus) and acidic groups (E, D, C-terminus), featuring more than one protomer, are taken into account.…”

Section: Introductionmentioning

confidence: 99%

On the Zwitterionic Nature of Gas-Phase Peptides and Protein Ions

et al. 2010

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Determining the total number of charged residues corresponding to a given value of net charge for peptides and proteins in gas phase is crucial for the interpretation of mass-spectrometry data, yet it is far from being understood. Here we show that a novel computational protocol based on force field and massive density functional calculations is able to reproduce the experimental facets of well investigated systems, such as angiotensin II, bradykinin, and tryptophan-cage. The protocol takes into account all of the possible protomers compatible with a given charge state. Our calculations predict that the low charge states are zwitterions, because the stabilization due to intramolecular hydrogen bonding and salt-bridges can compensate for the thermodynamic penalty deriving from deprotonation of acid residues. In contrast, high charge states may or may not be zwitterions because internal solvation might not compensate for the energy cost of charge separation.

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Section: Introductionmentioning

confidence: 99%

On the Zwitterionic Nature of Gas-Phase Peptides and Protein Ions

et al. 2010

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“…AMBER calculations of Gill et al 19 showed that lowenergy conformers of nonzwitterionic and zwitterionic [BK + 2H] 2+ (in the former, the guanidine groups of both Arg 1 and Arg 9 are protonated; in the latter, Arg 1 , Arg 9 , and the N-terminal amino group are protonated, and the C-terminal carboxylic group is deprotonated) have similar collision cross-sections. In the work of Cassady and co-workers, 20,21 molecular mechanics/ dynamics modeling using CHARMM reveals a low-energy nonzwitterionic structure that has the protonated guanidine groups occupying opposite ends of a compact conformation with the guanidine groups folded back onto the peptide backbone and interacting with carbonyl oxygen atoms via hydrogen bonds. Hydrogen/deuterium exchange experiments of Levy-Seri et al 22 confirmed compact conformation(s) for [BK + 2H] 2+ ; in addition, two non-interconverting populations were observed.…”

Section: Introductionmentioning

confidence: 99%

“…In summary, conflicting conclusions abound for the structures of [BK + 2H] 2+ ; earlier studies favored extended conformations, 2,3 while later work implied or reported compact structures that were zwitterionic 9,12,22 or nonzwitterionic. 6,20,21 Relatively little is known about [BK + 3H] 3+ ions. 8,11,13 The collision cross-section of [BK + 3H] 3+ is considerably larger than those of [BK + 2H] 2+ and [BK + H] + , which are almost identical; this means that [BK + 3H] 3+ is considerably more extended than the lower-charged BK ions.…”

Section: Introductionmentioning

confidence: 99%

Gaseous Bradykinin and Its Singly, Doubly, and Triply Protonated Forms: A First-Principles Study

et al. 2006

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The conformers of gaseous bradykinin, BK, (Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-Pro(7)-Phe(8)-Arg(9)) and its protonated forms, [BK + H](+), [BK + 2H](2+), and [BK + 3H](3+), were examined theoretically using a combination of the Merck molecular force field, Hartree-Fock, and density functional theory. Neutral BK, [BK + H](+), and [BK + 2H](2+) exist in zwitterionic forms that are stabilized by internal solvation and have compact structures; [BK + 3H](3+) differs by the absence of a salt bridge and adopts an elongated form. The common structural feature in all four BK species is a beta-turn in the Ser(6)-Pro(7)-Phe(8)-Arg(9) sequence. The gas-phase basicity of [BK + H](+) estimated from the calculated protonation energy is in accord with published experimental basicity; population-weighted collision cross-sections of the three ionic forms are in agreement with experimental cross-sections in the literature.

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“…Therefore, peptides identified in only one charge state, constituting about 75% of identified HSA peptides, were rejected if their charge state did not match the NBR, with the following exceptions. When basic groups were adjacent, one lower charge state was permitted for each such pair (43)(44). Because of possible long range interactions and involvement of less basic peptides (42), peptides of sequence length greater than 20 containing multiple basic sites were not subject to this filter.…”

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confidence: 99%

Tandem Mass Spectral Libraries of Peptides in Digests of Individual Proteins: Human Serum Albumin (HSA)

Dong

Yan

Kilpatrick

et al. 2014

Molecular & Cellular Proteomics

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This work presents a method for creating a mass spectral library containing tandem spectra of identifiable peptide ions in the tryptic digestion of a single protein. Human serum albumin (HSA 1 ) was selected for this purpose owing to its ubiquity, high level of characterization and availability of digest data. The underlying experimental data consisted of ϳ3000 one-dimensional LC-ESI-MS/MS runs with ion-trap fragmentation. In order to generate a wide range of peptides, studies covered a broad set of instrument and digestion conditions using multiple sources of HSA and trypsin. Computer methods were developed to enable the reliable identification and reference spectrum extraction of all peptide ions identifiable by current sequence search methods. This process made use of both MS2 (tandem) spectra and MS1 (electrospray) data. Identified spectra were generated for 2918 different peptide ions, using a variety of manually-validated filters to ensure spectrum quality and identification reliability. Shotgun proteomics is a widely used and evolving method for determining the protein composition of a biological mixture (1-3). It most often involves the digestion of denatured proteins by trypsin, followed by the identification of product peptides and the use of this information to infer protein identities and possibly targeted post-translational modifications (PTMs)1 . However, because digestion is a highly complex chemical process, a large proportion of identifiable products are not specifically targeted for analysis and therefore invisible to the analysis. These include unexpected and unwanted peptides that interfere with the analysis. Others may contain modifications of biological origin, which, unless specifically targeted, can be lost among the forest of artifacts (4 -6). This paper describes methods for building a tandem mass spectral library capable of characterizing all identifiable peptides in a tryptic digest of a selected protein. Spectral libraries are known to provide an effective way of reusing this information to quickly, reliably, and sensitively determine peptide identities (7-11). These identifications can serve several purposes, including 1) ensuring that all previously identified peptides are identified regardless of search engine settings, 2) tagging artifact peptides that might otherwise lead to false positive identifications, 3) ensuring the identification of known and identifiable biological post-translational modifications without explicitly looking for them, and 4) providing a list of artifact peptides for assessing the quality of the sample preparation process.HSA, human serum albumin, was selected as the target protein for library development partly because of its ubiquity, making up Ͼ50% of the total protein in blood (12-13) and therefore found in many biological samples, and partly because of the considerable background information available

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Effects of peptide chain length on the gas-phase proton transfer properties of doubly-protonated ions from bradykinin and its N-terminal fragment peptides

Cited by 18 publications

References 69 publications

On the Zwitterionic Nature of Gas-Phase Peptides and Protein Ions

On the Zwitterionic Nature of Gas-Phase Peptides and Protein Ions

Gaseous Bradykinin and Its Singly, Doubly, and Triply Protonated Forms: A First-Principles Study

Tandem Mass Spectral Libraries of Peptides in Digests of Individual Proteins: Human Serum Albumin (HSA)

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