QUDeX-MS: hydrogen/deuterium exchange calculation for mass spectra with resolved isotopic fine structure

BMC Bioinformatics

Jeffrey N Agar¹  Qian Liu¹  Joseph P Salisbury¹ 

[1]Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences and Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, Boston 02115, MA, USA

关键词: Protein analysis;    Protein structure;    Mass spectrometry;    Fourier transform ion cyclotron resonance;    Isotopic fine structure;    Hydrogen/deuterium exchange;   

Others  :  1084430
DOI  :  10.1186/s12859-014-0403-1

 received in 2014-06-27, accepted in 2014-12-01,  发布年份 2014

【 摘 要 】

Background

Hydrogen/deuterium exchange (HDX) coupled to mass spectrometry permits analysis of structure, dynamics, and molecular interactions of proteins. HDX mass spectrometry is confounded by deuterium exchange-associated peaks overlapping with peaks of heavy, natural abundance isotopes, such as carbon-13. Recent studies demonstrated that high-performance mass spectrometers could resolve isotopic fine structure and eliminate this peak overlap, allowing direct detection and quantification of deuterium incorporation.

Results

Here, we present a graphical tool that allows for a rapid and automated estimation of deuterium incorporation from a spectrum with isotopic fine structure. Given a peptide sequence (or elemental formula) and charge state, the mass-to-charge ratios of deuterium-associated peaks of the specified ion is determined. Intensities of peaks in an experimental mass spectrum within bins corresponding to these values are used to determine the distribution of deuterium incorporated. A theoretical spectrum can then be calculated based on the estimated distribution of deuterium exchange to confirm interpretation of the spectrum. Deuterium incorporation can also be detected for ion signals without a priori specification of an elemental formula, permitting detection of exchange in complex samples of unidentified material such as natural organic matter. A tool is also incorporated into QUDeX-MS to help in assigning ion signals from peptides arising from enzymatic digestion of proteins. MATLAB-deployable and standalone versions are available for academic use at qudex-ms.sourceforge.net webcite and agarlabs.com webcite.

Conclusion

Isotopic fine structure HDX-MS offers the potential to increase sequence coverage of proteins being analyzed through mass accuracy and deconvolution of overlapping ion signals. As previously demonstrated, however, the data analysis workflow for HDX-MS data with resolved isotopic fine structure is distinct. QUDeX-MS we hope will aid in the adoption of isotopic fine structure HDX-MS by providing an intuitive workflow and interface for data analysis.

【 授权许可】

   
2014 Salisbury et al.; licensee BioMed Central.

【 图 表 】

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