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

尽管现有的结构生物学工具具有强大的功能，但药物/抑制剂发现过程的许多方面仍然没有得到现有工具的很好服务。在许多情况下，实际限制意味着无法以足够的数量(药物开发的每个步骤没有足够的结构)、以足够的精度(结构数据的模糊性)、甚至根本不能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，晶体结构具有无法解决的无序区域的情况，配体接触处结构的精确度不足以驱动药物发现过程的情况，蛋白质很难以足够的数量生产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的情况。在这个项目中，我们将进一步开发EVV 2DIR光谱的应用到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。

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.