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

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.