Constrained De Novo Sequencing of Conotoxins

peer-reviewed · Journal of Proteome Research · 2012

peer-reviewed · Journal of Proteome Research · 2012. Swapnil Bhatia et al. De novo peptide sequencing by mass spectrometry (MS) can determine the amino acid sequence of an unknown…
Date 2012-08-03
Type peer-reviewed
Venue Journal of Proteome Research
Publisher American Chemical Society (ACS)
Contribution algorithm
DOI 10.1021/pr300312h
Citations (OpenAlex) 34
Venue 2-year citedness 3.83

Abstract

De novo peptide sequencing by mass spectrometry (MS) can determine the amino acid sequence of an unknown peptide without reference to a protein database. MS-based de novo sequencing assumes special importance in focused studies of families of biologically active peptides and proteins, such as hormones, toxins, and antibodies, for which amino acid sequences may be difficult to obtain through genomic methods. These protein families often exhibit sequence homology or characteristic amino acid content; yet, current de novo sequencing approaches do not take advantage of this prior knowledge and, hence, search an unnecessarily large space of possible sequences. Here, we describe an algorithm for de novo sequencing that incorporates sequence constraints into the core graph algorithm and thereby reduces the search space by many orders of magnitude. We demonstrate our algorithm in a study of cysteine-rich toxins from two cone snail species (Conus textile and Conus stercusmuscarum) and report 13 de novo and about 60 total toxins.

Authors

  1. Swapnil Bhatia · Boston University, Palo Alto Research Center
  2. Yong J. Kil · Palo Alto Research Center, Protein Metrics (United States), Protein Metrics Inc.
  3. Beatrix Ueberheide · NYU Langone Medical Center, Rockefeller University
  4. Brian T. Chait · Rockefeller University
  5. Lemmuel L. Tayo · Mapua Institute of Technology, Mapúa University, University of the Philippines Diliman, University of the Philippines System
  6. Lourdes J. Cruz · University of the Philippines Diliman, University of the Philippines System
  7. Bingwen Lu · Pfizer (United States), Pfizer Inc., Princeton University, The Scripps Research Institute, University of Southern California
  8. John R. Yates III · The Scripps Research Institute
  9. Marshall Bern · Palo Alto Research Center, Protein Metrics (United States), Protein Metrics Inc.

Methods and tools

  • Conovo: Constrained de novo sequencing algorithm for peptide families such as conotoxins.

Cites (14)

Cited by (9)

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