HDX Workbench: Software for the Analysis of H/D Exchange MS Data

Pascal, Bruce D.; Willis, Scooter; Lauer, J.; Landgraf, Rachelle R.; West, Graham M.; Marciano, David P.; Novick, Scott J.; Goswami, Devrishi; Chalmers, Michael J.; Griffin, Patrick R.

doi:10.1007/s13361-012-0419-6

Cited by 266 publications

(251 citation statements)

References 34 publications

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“…mAb1-bound GCGR or antibody-free vs . mAb23-bound GCGR) were run separately under the same conditions and percent deuterium exchange values for peptide isotopic envelopes at each time point were calculated and processed using the Workbench software 36 .…”

Section: Methodsmentioning

confidence: 99%

“… a , Heat map view of the GCGR-NNC0640-mAb1 complex colored according to the heat map coloring scheme used by the software HDX Workbench 36 . Each bar represents a peptide showing the average difference (across 6 time points) in D 2 O uptake between the receptor-antibody complex and the antibody-free receptor with the standard deviation between replicates and the peptide charge states shown in parentheses.…”

Section: Extended Datamentioning

confidence: 99%

See 1 more Smart Citation

Structure of the full-length glucagon class B G-protein-coupled receptor

Zhang

Qiao

Yang

et al. 2017

Nature

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185

172

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The human glucagon receptor (GCGR) belongs to the class B G protein-coupled receptor (GPCR) family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 Å crystal structure of full-length GCGR containing both extracellular domain (ECD) and transmembrane domain (TMD) in an inactive conformation. The two domains are connected by a 12-residue segment termed the ‘stalk’, which adopts a β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of GCGR-TMD. The first extracellular loop (ECL1) exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-sheet structure. Hydrogen/deuterium exchange, disulfide cross-linking and molecular dynamics studies suggest that the stalk and ECL1 play critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding about the signaling mechanisms of class B GPCRs.

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Section: Methodsmentioning

confidence: 99%

Section: Extended Datamentioning

confidence: 99%

Structure of the full-length glucagon class B G-protein-coupled receptor

Zhang

Qiao

Yang

et al. 2017

Nature

Self Cite

185

172

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show abstract

“…The resultant m/z that fell between +7 to -7 ppm (as defined by user input) were used to create single ion chromatograms (SIC) from the mass spectral data. The chromatographic peaks were then used to hone in on the possible retention times of the peptide and to determine the presence of the peptide and best retention time ranges in the MS 1 data using methods that have been described previously [63,66,67].…”

Section: Methodsmentioning

confidence: 99%

“…Although these efforts do not focus solely on the PTM identification problem and do not use the MS 1 interrogation as a central and initial method, they do highlight the value of the spectral data available in MS 1 . To date the only work to specifically search for PTM peptides using the information present in MS 1 data was presented recently [63,64].…”

Section: Introductionmentioning

confidence: 99%

Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications

Pascal

West

Scharager-Tapia

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. The goal in proteomics to identify all peptides in a complex mixture has been largely addressed using various LC MS/MS approaches, such as data dependent acquisition, SRM/MRM, and data independent acquisition instrumentation. Despite these developments, many peptides remain unsequenced, often due to low abundance, poor fragmentation patterns, or data analysis difficulties. Many of the unidentified peptides exhibit strong evidence in high resolution MS 1 data and are frequently post-translationally modified, playing a significant role in biological processes. Proteomics Workbench (PWB) software was developed to automate the detection and visualization of all possible peptides in MS 1 data, reveal candidate peptides not initially identified, and build inclusion lists for subsequent MS 2 analysis to uncover new identifications. We used this software on existing data on the autophagy regulating kinase Ulk1 as a proof of concept for this method, as we had already manually identified a number of phosphorylation sites Dorsey, F. C. et al (J. Proteome. Res. 8(11), 5253-5263 (2009)). PWB found all previously identified sites of phosphorylation. The software has been made freely available at http://www.proteomicsworkbench.com.

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“…Its extension, MTMDAT-HADDOCK, 18 allows the visualization of protein interactions. HDX data can be analyzed with the aid of QUDeX-MS, 19 which allows the estimation of deuterium incorporation, or HDX workbench, 20 Hydra, 21 or Hexicon, 22 which allow management and visualization of HDX data. All of these tools are, however, approach-specific and are aimed primarily at mass spectrometrists with a specific focus on the experimental mass spectrometry data and their processing and interpretation.…”

Section: ■ Conclusionmentioning

confidence: 99%

PepShell: Visualization of Conformational Proteomics Data

et al. 2015

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Proteins are dynamic molecules; they undergo crucial conformational changes induced by post-translational modifications and by binding of cofactors or other molecules. The characterization of these conformational changes and their relation to protein function is a central goal of structural biology. Unfortunately, most conventional methods to obtain structural information do not provide information on protein dynamics. Therefore, mass spectrometry-based approaches, such as limited proteolysis, hydrogen−deuterium exchange, and stable-isotope labeling, are frequently used to characterize protein conformation and dynamics, yet the interpretation of these data can be cumbersome and time consuming. Here, we present PepShell, a tool that allows interactive data analysis of mass spectrometry-based conformational proteomics studies by visualization of the identified peptides both at the sequence and structure levels. Moreover, PepShell allows the comparison of experiments under different conditions, including different proteolysis times or binding of the protein to different substrates or inhibitors.

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HDX Workbench: Software for the Analysis of H/D Exchange MS Data

Cited by 266 publications

References 34 publications

Structure of the full-length glucagon class B G-protein-coupled receptor

Structure of the full-length glucagon class B G-protein-coupled receptor

Software Analysis of Uncorrelated MS1 Peaks for Discovery of Post-Translational Modifications

PepShell: Visualization of Conformational Proteomics Data

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