Ligand Binding to Biomolecular Targets Studied by Electron-Vibration-Vibration Two Dimensional Infrared Spectroscopy

通过电子振动二维红外光谱研究配体与生物分子靶标的结合

• 批准号: 2275870
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2275870
• 关键词: Ligand; Binding; Biomolecular; Targets; Studied

Despite the power of the existing tools of structural biology, there are many aspects of the drug/inhibitor discovery process that are still not well-served by existing tools. There are many cases where practical limitations mean that the desired information cannot be retrieved in sufficient quantity (not enough structures for each step of drug development), with sufficient precision (ambiguity in the structural data), or even at all using existing techniques. This includes for example, cases where the protein cannot be crystallised, where the crystal structure has regions of disorder which cannot be resolved, where the precision of the structure at ligand contact is insufficient for driving the drug discovery process, where the protein is hard to produce in sufficient quantities or where the region of interest in the protein is relatively unstructured in its native condition.In this project we will further develop the application of EVV 2DIR spectroscopy to 1) The detection of ligand binding 2) An assessment of the contacts of ligand binding 3) Determination of the complete geometry of the ligand-target interaction.

尽管结构生物学的现有工具的力量，有许多方面的药物/抑制剂的发现过程中，仍然没有很好地服务于现有的工具。在许多情况下，实际的限制意味着无法以足够的数量（没有足够的结构用于药物开发的每个步骤）、足够的精度（结构数据中的模糊性）或甚至根本无法使用现有技术来检索所需的信息。这包括例如蛋白质不能结晶的情况，晶体结构具有不能分辨的无序区域的情况，配体接触处的结构精度不足以驱动药物发现过程的情况，其中蛋白质很难产生足够的数量，或者蛋白质中的感兴趣区域在其天然条件下相对非结构化。在这个项目中，我们将进一步发展EVV 2D光谱在1）配体结合的检测2）配体结合的接触的评估3）配体-靶相互作用的完整几何形状的确定方面的应用。