Research Program

The wide range of extraordinary properties displayed by proteins, such as specific ligand binding, high catalytic activity, and ligand-induced conformational changes, allows them to carry out complex molecular processes with extreme precision and efficiency. Because of these properties, many proteins are being exploited for a large number of applications in industry and research. Although various useful properties from natural proteins are being exploited, novel properties not found in nature are required to expand the applications possible for proteins in industry and research. To access these desired new properties, scientists use protein engineering and design techniques. Protein engineering and design have yielded many successes, yet the identification of protein sequences that will display the desired properties remains a formidable challenge due to the vastness of sequence space that one must sample to identify beneficial mutations. To help overcome the inherent difficulties of protein engineering, computational protein design (CPD) algorithms have been developed. The power of CPD results from its capability to perform virtual screening of sequence spaces astronomically larger (>10E80 sequences) than those that can be experimentally tested. Our research group exploits CPD algorithms to achieve three long-term aims, which are (1) to create new proteins for chemical and biological applications, (2) to develop new computational methods to more efficiently engineer proteins, and (3) to gain fundamental knowledge about the determinants of protein function using a design-based approach instead of the traditional perturbation-based approach.



The research approach used in the Chica lab (Fig. 1) consists of (1) computational design of focused combinatorial mutant libraries, (2) construction of these libraries by molecular biology techniques, (3) screening or selection of the libraries to identify mutants with the desired properties, and (4) extensive characterization of these mutants using a variety of kinetic or spectroscopic assays. The Chica lab’s multidisciplinary research program encompasses both experimental and computational work, and is located at the interface between biochemistry, chemistry, and computer science.


Research Projects

1. Development and experimental validation of multistate computational protein design methods.

2. Designer biocatalysts for asymmetric synthesis of unnatural amino acids.

3. Fluorescent protein engineering and development of biosensors for developmental biology.



Our state-of-the-art Protein Engineering and Computational Protein Design Laboratory was funded through the Canada Foundation for Innovation. It is equipped with infrastructure required to engineer proteins. This includes a computer cluster to run high-performance computer simulations as well as equipment to build DNA libraries, express & purify proteins, and assay protein properties.