Developing NMR and Biophysical Strategies to Study Protein-Ligand Interactions and Reveal Interesting Compound Properties

开发核磁共振和生物物理策略来研究蛋白质-配体相互作用并揭示有趣的化合物特性

• 批准号: RGPIN-2016-06747
• 负责人: LaPlante, Steven
• 金额: $ 2.19万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632542
• 关键词: Developing; NMR; Biophysical; Strategies; Study

There is a widely held view that the study of ligands binding to macromolecules should be simple and straightforward. In practice, however, the available tools are sparse and compromised by artifacts. Moreover, binding involves many events, some of which have yet to be fully revealed. This research program aims to develop strategies to enable the elucidation of various binding events and to expose relevant free-state properties of small-molecule ligands. The research will be executed within the context of mounting fragment-based ligand discovery (FBLD) efforts in my laboratory where the binding of thousands of compounds to a variety of protein types will be systematically evaluated. Briefly, FBLD will involve the screening of libraries (e.g. ~1000-8000 members) of fragment compounds (~120-300 Da) in search for binders (K

人们普遍认为，配体与大分子结合的研究应该简单明了。然而，在实践中，可用的工具是稀疏的，并受到工件的影响。此外，绑定涉及许多事件，其中一些尚未完全揭示。该研究计划旨在制定策略，以阐明各种结合事件，并暴露小分子配体的相关自由态特性。该研究将在我的实验室中进行基于片段的配体发现（FBLD）工作，其中将系统地评估数千种化合物与各种蛋白质类型的结合。简言之，FBLD将涉及筛选片段化合物（~120-300 Da）的文库（例如~1000-8000个成员）以寻找结合剂（K