Christoph Borchers

Christoph Borchers
McGill University

Talk Title:
“I have a dream: From the protein sequence to its structure – modern structural proteomics techniques”

Dr. Borchers received his PhD from the University of Konstanz, Germany. After his post-doctoral and staff scientist positions at NIEHS/NIH (NC, USA), he became the director of the University of North Carolina-Duke Proteomics Facility and held a faculty position at the UNC Medical School (2001-2006). Since 2006, Dr. Borchers has been at the University of Victoria (UVic), BC, Canada, where he currently has a Professorship in the Dept. of Biochemistry and Microbiology, the Rix BC Leadership Chair in Biomedical and Environmental Proteomics, and Directorship of the UVic-Genome BC Proteomics Centre. Dr. Borchers is also a Professor in the Dept. of Oncology at McGill University (Montreal, Canada), and holds the Segal Chair in Molecular Oncology. Dr. Borchers’ research involves the improvement, development, and application of proteomics and metabolomics technologies, especially quantitative techniques for clinical diagnostics; his research also involves the application of protein chemistry and MS to problems in structural proteomics.

We present here an integrated experimental and computational approach for de novo protein structure determination in which short-distance crosslinking data is incorporated into rapid discrete molecular dynamic (DMD) simulations as constraints, reducing the conformational space and achieving the correct protein folding on practical time scales. We tested our approach on myoglobin and FKBP — models for alpha-helix and beta-sheet rich proteins, respectively — and found that the lowest-energy structures obtained were in excellent agreement with the crystal structure and with hydrogen/deuterium exchange, surface modification, and long-distance crosslinking validation data. Our approach is readily applicable to other proteins with unknown structures.