NMR Training Course: Day 4: Ligand discovery by NMR - methods, experiments, data analysis Synopsis Ben Davis, Vernalis R&D In this short course, we will review the methods and key experiments used to identify and characterise ligand:receptor interactions by NMR. The focus will be on the practical aspects of ligand discovery, both in terms of NMR methods and of sample requirements and preparation. We will also discuss the applicability and limitations of various NMR methods when applied to ligand discovery. These NMR methods will include Ligand observed experiments STD, Water-LOGSY, Relaxation filtered experiments Diffusion filtered experiments Transferred NOEs, ILOEs, and INPHARMA methods Protein observed experiments Homonuclear experiments 15N-1H and 13C-1H HSQC, STD-HSQC Filtered and/or edited NOE experiments We may also discuss applications to other macromolecules (e.g. nucleic acids) if time allows. One of the key aspects of ligand identification, by any method, is the consideration of possible artefacts and the identification of false positive and false negative results. We will cover a range of common problems which can occur when identifying and characterising ligands by NMR and other biophysical methods, and some of the ways of recognising these when they (inevitably) occur. We will discuss methods of data analysis; this will cover both software packages used, and good working practices which can assist data analysis. It is also intended that there will be a practical session where we will acquire data on a test system, and to analyse this data as discussed in the course.