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

有一种广泛的观点认为，研究配体与大分子的结合应该简单明了。然而，在实践中，可用的工具很少，而且会受到构件的影响。此外，绑定涉及许多事件，其中一些事件尚未完全揭示。这项研究计划旨在开发能够阐明各种结合事件的策略，并揭示小分子配体的相关自由态性质。这项研究将在我的实验室进行基于片段的配体发现(FBLD)工作的背景下进行，在那里将系统地评估数千种化合物与各种蛋白质类型的结合。简而言之，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

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