SIM-XL: a tool for identifying cross

Sociedade Brasileira de Espectrometria de Massas – BrMASS
PRO – PROTEINS AND PEPTIDES
SIM-XL: a tool for identifying cross-linked peptides
in complex protein mixtures
Diogo B Lima1, Tatiani Brenelli Lima2, Ana Gisele Neves Ferreira3, Valmir C Barbosa4,
Tiago S Balbuena5, Fabio Cesar Gozzo2*, Paulo Costa Carvalho1*
Corresponding: [email protected]; [email protected]
1. Laboratory for Proteomics and Protein Engineering, Carlos Chagas Institute,
Fiocruz, Paraná
2. Dalton Mass Spectrometry Laboratory, IQ-Unicamp, Campinas-SP
3. Laboratory for Toxinology, Fiocruz, Rio de Janeiro
4. Systems Engineering and Computer Science Program, COPPE, Federal
University of Rio de Janeiro
5. Laboratório de Proteômica Vegetal, Universidade Estadual Paulista,
Jaboticabal-SP
State of the art structural mass spectrometry based proteomics is often accomplished by
using cross-linkers to covalently bind two or more reactive groups.
This strategy is
complementary to classical structural biology and therefore broadens the toolset for analyzing
protein and protein-protein complex structures. One of the greatest challenges in identifying
cross-linked peptides in complex protein mixtures is computationally dealing with the large
search space which grows exponentially with each peptide included in the sequence database.
Here, we present the preliminary results of an algorithm to deal with this problem termed
Spectrum Identification Machine for Cross-Linked peptides (SIM-XL).
It capitalizes on
experimental features that allow us to effectively address the massive combinatorial problem at
hand. We evaluated our method in a gold standard proteomic complex dataset by first using a
sequence database limited to the proteins in the existing complex. To simulate a complex
mixture scenario, we then included all proteins from the P. furiosus dataset in the sequence
database; our strategy could quickly reproduce the results using the simplified database when a
competing tool, Cross-Work, failed to do so. As such SIM-XL will be recommended for dealing
with the studies of protein-structure and protein-protein-interaction in either simple or complex
protein mixtures. It has a desktop graphic user interface but is also being designed for cloud
computing. SIM-XL is integrated into the PatternLab for proteomics environment which offers
a wide range of tools for downstream analysis for quantitative proteomics.
5º Congresso BrMass – 7 a 11 de Dezembro de 2013