Computational Chemogenomics
Recent advances in functional genomics methods, including the development of specialized transduction systems for high-throughput construction of uniquely tagged mutants, produced detailed information on the roles of individual bacterial genes in the functioning of pathogens.
In the case of Mycobacterium tuberculosis, about 700 genes (out of approximately 4,000) are identified as essential for bacterial growth. As only a dozen of these genes are targeted by existing drugs, these advances create an unprecedented opportunity for development of novel therapeutic agents active against bacteria resistant to drugs in current clinical use.
The objective of computational chemogenomics at Trudeau Institute is to make effective use of these genomic findings to identify small molecule probes, tool compounds, leads for optimization, and drug candidates for clinical development.
As mechanisms of action and spectrum of activities of many experimental and approved drugs are not fully understood, we employ methods of structural bioinformatics, chemoinformatics, and 3D molecular modeling to analyze large compendiums of drugs developed by the biopharmaceutical industry for various indications over the last 50 years, aiming to identify well characterized, synthetically accessible molecules with previously unappreciated activity against pathogens of interest.