'TOF2H': A precision toolbox for rapid, high density/high coverage hydrogen-deuterium exchange mass spectrometry via an LC-MALDI approach, covering the data pipeline from spectral acquisition to HDX rate analysis

Autor: Paul D. Gershon, Pornpat Nikamanon, Marek D. Koter, Elroy Pun, Wayne Chou
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Materials science
Protein Conformation
Analytical chemistry
Surface binding
Information Storage and Retrieval
High density
Bioinformatics
Mass spectrometry
High coverage
lcsh:Computer applications to medicine. Medical informatics
Sensitivity and Specificity
01 natural sciences
Biochemistry
Rate analysis
03 medical and health sciences
Structural Biology
Physical Sciences and Mathematics
Molecular Biology
lcsh:QH301-705.5
030304 developmental biology
0303 health sciences
model
Applied Mathematics
010401 analytical chemistry
Deuterium Exchange Measurement
Proteins
Chromatography liquid
Life Sciences
proteins
0104 chemical sciences
Computer Science Applications
lcsh:Biology (General)
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
lcsh:R858-859.7
Hydrogen–deuterium exchange
Algorithms
Software
Chromatography
Liquid
Research Article
Zdroj: BMC Bioinformatics, Vol 9, Iss 1, p 387 (2008)
Nikamanon, Pornpat; Pun, Elroy; Chou, Wayne; Koter, Marek D; & Gershon, Paul D. (2008). "TOF2H": A precision toolbox for rapid, high density/high coverage hydrogen-deuterium exchange mass spectrometry via an LC-MALDI approach, covering the data pipeline from spectral acquisition to HDX rate analysis. BMC BIOINFORMATICS, 9, 387-387. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/25f1c9h7
BMC Bioinformatics
ISSN: 1471-2105
Popis: Background Protein-amide proton hydrogen-deuterium exchange (HDX) is used to investigate protein conformation, conformational changes and surface binding sites for other molecules. To our knowledge, software tools to automate data processing and analysis from sample fractionating (LC-MALDI) mass-spectrometry-based HDX workflows are not publicly available. Results An integrated data pipeline (Solvent Explorer/TOF2H) has been developed for the processing of LC-MALDI-derived HDX data. Based on an experiment-wide template, and taking an ab initio approach to chromatographic and spectral peak finding, initial data processing is based on accurate mass-matching to fully deisotoped peaklists accommodating, in MS/MS-confirmed peptide library searches, ambiguous mass-hits to non-target proteins. Isotope-shift re-interrogation of library search results allows quick assessment of the extent of deuteration from peaklist data alone. During raw spectrum editing, each spectral segment is validated in real time, consistent with the manageable spectral numbers resulting from LC-MALDI experiments. A semi-automated spectral-segment editor includes a semi-automated or automated assessment of the quality of all spectral segments as they are pooled across an XIC peak for summing, centroid mass determination, building of rates plots on-the-fly, and automated back exchange correction. The resulting deuterium uptake rates plots from various experiments can be averaged, subtracted, re-scaled, error-barred, and/or scatter-plotted from individual spectral segment centroids, compared to solvent exposure and hydrogen bonding predictions and receive a color suggestion for 3D visualization. This software lends itself to a "divorced" HDX approach in which MS/MS-confirmed peptide libraries are built via nano or standard ESI without source modification, and HDX is performed via LC-MALDI using a standard MALDI-TOF. The complete TOF2H package includes additional (eg LC analysis) modules. Conclusion "TOF2H" provides a comprehensive HDX data analysis package that has accelerated the processing of LC-MALDI-based HDX data in the authors' lab from weeks to hours. It runs in a standard MS Windows (XP or Vista) environment, and can be downloaded http://tof2h.bio.uci.edu or obtained from the authors at no cost.
Databáze: OpenAIRE
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