Reducing mass degeneracy in SAR by MS by stable isotopic labeling

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
C Bailey-KelloggB R Donald

Abstract

Mass spectrometry (MS) promises to be an invaluable tool for functional genomics, by supporting low-cost, high-throughput experiments. However, large-scale MS faces the potential problem of mass degeneracy---indistinguishable masses for multiple biopolymer fragments (e.g., from a limited proteolytic digest). This paper studies the tasks of planning and interpreting MS experiments that use selective isotopic labeling, thereby substantially reducing potential mass degeneracy. Our algorithms support an experimental--computational protocol called structure-activity relation by mass spectrometry (SAR by MS) for elucidating the function of protein-DNA and protein-protein complexes. SAR by MS enzymatically cleaves a crosslinked complex and analyzes the resulting mass spectrum for mass peaks of hypothesized fragments. Depending on binding mode, some cleavage sites will be shielded; the absence of anticipated peaks implicates corresponding fragments as either part of the interaction region or inaccessible due to conformational change upon binding. Thus, different mass spectra provide evidence for different structure--activity relations. We address combinatorial and algorithmic questions in the areas of data analysis (constraining bindin...Continue Reading

References

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Dec 7, 2000·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·C Bailey-KelloggB R Donald

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Citations

Dec 19, 2001·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·T ChenG M Church
Apr 20, 2004·Assay and Drug Development Technologies·Ricardo A GarciaFrancisco J Villarreal
Nov 24, 2004·Protein Science : a Publication of the Protein Society·Xiaoduan YeChris Bailey-Kellogg
Jan 5, 2008·Bioorganicheskaia khimiia·T V MinaevaM A Grachev

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