Increasing the speed and accuracy of proteomics protocols through the development of accurate peptide retention prediction models in RP-HPLC

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Significant breakthroughs in development of mass-spectrometry (MS) and liquid chromatography (LC) in the past two decades now provide unprecedented capabilities for studies in biological and health sciences. My group's research has focused on the development of peptide retention prediction models in liquid chromatography, and their application to practical proteomic analysis: accurate peptide retention prediction will allow significant increase in overall resolution and performance of LC-MS systems. The overarching goal of my research program is the development of a comprehensive physico-chemical model of peptide interaction with hydrophobic chromatographic media. In addition to representing significant advances in chromatographic science, this research will also help in the understanding of protein/peptide interactions with hydrophobic biological membranes - one of the key processes in cell biology and biochemical studies. Since its publication in 2004, our Sequence Specific Retention Calculator model has become a benchmark tool in the field, attracting attention from the general proteomics community. The University of Manitoba and one of the leading manufacturers of proteomic equipment and software, ThermoFisher Scientific, signed a licensing agreement in October 2010 to incorporate SSRCalc into the analytical software of their instruments, further indicating importance of this topic and our leadership in this field. We propose further improvements to the SSRCalc algorithm's accuracy through the physico-chemical modeling of the stabilization of alpha-helical structures upon interaction with hydrophobic stationary phase. We also plan to develop new applied approaches that will increase both the speed and capacity of LC-MS analyses using the fast on-the-fly generation of peptide exclusion/inclusion lists using high performance commodity graphics cards as peptide identification engines.