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

Davey et al., Nature Chemical Biology, 2017, 13, 1280-1285.

This manuscript presents the first demonstration of the rational design of proteins that can spontaneously exchange between two predefined conformational states in the absence of an external stimulus, and on a timescale relevant to function. To achieve this result, we developed a broadly-applicable computational method to engineer protein dynamics that we term meta-multistate design (meta-MSD). We used meta-MSD to design spontaneous exchange between two novel conformations introduced into the global fold of protein G domain β1 (Gβ1). The designed proteins, named DANCERs, for Dynamic And Native Conformational ExchangeRs, are stably folded and exchange between predicted conformational states on the millisecond timescale. Our new method for design of conformational exchange paves the way to the design of proteins with a more versatile range of functions than was previously possible, such as those that must adopt more than one conformational state (e.g., enzymes, molecular rotors, biosensors).

Previous results can be found here.

 

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