Understanding mechanism of action: Combined computational and structural biology studies to determine small molecule effects on protein dynamics and function

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Cotinga Pharmaceuticals, a Canadian biopharma company, and the University of Windsor, professors John Trant, Yufeng Tong, and Lisa Porter will be collaborating on understanding the mechanisms of action for small molecules and certain proteins that are found in many cancers. When proteins become mutated, they cease to function properly and this can allow cells to grow uncontrollably causing disease. Often the mutation simply involves changing one of the thousands of amino acids that make up the protein for a different amino acid. This is often enough to cause the protein to adopt a different shape. This prevents it from doing its job in the cell. Cotinga has developed several drugs in clinical trials and needs to better understand how they interact with specific human proteins. The UWindsor team will be using a combination of computer simulations of the protein-molecule interactions and experimental measurements of these interactions. The team will also be using crystallography to get "pictures" of the molecules interacting with the proteins to make sure that they are the true targets of these molecules. This five year project will not only advance Cotinga's science, it will also help us better understand how molecules can help misfolded proteins regain their proper shape, why proteins fold the way they do, and why proteins interact with other proteins the way they do. This project consequently advances the economic interests of a Canadian company, assists in providing exceptional multidisciplinary training to the students and postdoctoral fellows working on it preparing them for employment in the chemical industry, and also improves humanity's understanding of the basic behaviour of these very important proteins.