Ligand observed experiments

NMR Training Course: Day 4: Ligand discovery
by NMR - methods, experiments, data analysis
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.