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

了解作用机制：结合计算和结构生物学研究来确定小分子对蛋白质动力学和功能的影响

• 批准号: 555689-2020
• 负责人: Trant, JohnJF
• 金额: $ 11万
• 依托单位: University of Windsor
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748432
• 关键词: Understanding; mechanism; action; Combined; computational

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.

加拿大生物制药公司Cotinga Pharmaceuticals以及温莎大学，John Trant，Yufeng Tong和Lisa Porter教授将合作了解许多癌症中小分子和某些蛋白质的作用机理。当蛋白质突变时，它们就停止正常运行，这可以使细胞无法控制地引起疾病。通常，突变仅涉及更改构成不同氨基酸蛋白质的数千种氨基酸之一。这通常足以使蛋白质采用不同的形状。这样可以防止其在单元格中完成工作。 Cotinga在临床试验中开发了几种药物，需要更好地了解它们与特定人类蛋白的相互作用。 Uwindsor团队将使用计算机模拟的蛋白质 - 分子相互作用和这些相互作用的实验测量的组合。该团队还将使用晶体学来获取与蛋白质相互作用的分子的“图片”，以确保它们是这些分子的真正靶标。这个五年的项目不仅将推进科廷加的科学，还将帮助我们更好地理解分子如何帮助错误折叠的蛋白质恢复其适当的形状，为什么蛋白质折叠起来的方式以及为什么蛋白质以其方式与其他蛋白质相互作用。因此，该项目促进了加拿大公司的经济利益，协助为学生提供卓越的多学科培训，并为其在化学工业中就业做好准备，并提高人类对这些非常重要蛋白质的基本行为的理解。