Protein Engineering & Computational Protein Design

We specialize in the development of novel proteins with useful properties for their application in chemistry and biology. In particular, we are interested in developing designer biocatalysts for chemical synthesis as well as genetically-encoded biosensors based on fluorescent proteins for in vivo imaging applications. To achieve these goals, we develop and exploit multistate computational protein design methods to predict mutations leading to the desired protein property. More information on our research projects can be found in the Research section.

Latest Results

St-Jacques AD et al. (2019) ACS Catalysis 9, 5480-5485

Here, we developed a multistate computational protein design methodology named multichemical state analysis (MCSA), which can be used to optimize enzyme sequences for productive binding of multiple target substrates. We used MCSA to redesign the active site of branched-chain amino acid aminotransferase to accept both α-ketoglutarate and the non-native substrate L-histidine. Screening of a designed combinatorial library comprising 32 mutants for enhanced L-histidine transamination activity yielded four variants displaying up to ≈200-fold improvements to kcat/KM with the non-native substrate (12.5% hit rate), a library size several orders of magnitude smaller than was required to obtain similar activity enhancements in other aminotransferases with a single round of directed evolution. MCSA opens the door to the rational design of broad-specificity biocatalysts and multi-substrate enzymes displaying tailored specificity.

Previous results can be found here.

 

Advanced Protein Engineering Training, Internships, Courses & Exhibition (APRENTICE) Program

Interested in pursuing graduate training in protein engineering? Find out more about the APRENTICE program by clicking on the image below.

 

Research Funding

We gratefully acknowledge support from the following agencies:

 

Keywords

Protein Engineering, Computational Protein Design, Multistate Design, Enzymes, Biocatalysis, Fluorescent Proteins, Protein Dynamics, Molecular Modeling, Protein Science, High-Performance Computing, Biological Chemistry

 

Contact info

Roberto Chica, Ph. D.
Associate Professor
Department of Chemistry and Biomolecular Sciences
University of Ottawa
10 Marie Curie
Ottawa, ON K1N 6N5
Canada

(613) 562-5800 x 1988
rchica at uottawa dot ca