Deep knowledge of how the binding processes occur, such as drugreceptor,
signal transduction and cellular recognition, is indispensable for a greater
understanding of biological functions. Medicinal chemistry in the path of drug
discovery has focused on studies of the molecular interactions which are involved in
the development of severe disease state. Thereby, an accurate knowledge about the
underlying protein receptor-ligand recognition events at atomic level is fundamental
in the process to comprehension, identification and optimization of more potent drug
candidates. In this sense, several novel NMR spectroscopic techniques can yield
insight into protein-protein interactions in solutions at the molecular level.
Resonance signal of the protein or the ligand can be used to identify binding events
from a broad range of experiments. For this purpose, changes in NMR spectroscopy
parameters such as chemical shifts, relaxation times, diffusion constants, NOEs or
exchange of saturation can serve as a measure of binding. In this chapter, the main
NMR experimental approaches applied to characterize protein-ligand binding
affinity will be discussed. Thus, we hope to provide the reader with a broader and
better understanding of how NMR spectroscopy techniques can be applied to a drug
discovery process.
Keywords: 13C-labeled protein, 15N-labeled protein, binding affinity, diffusion
constant, diffusion ordered spectroscopy (dosy), drug discovery, hsqc
(heteronuclear single quantum coherence), intermolecular interaction, nmr
screening methods, nuclear magnetic resonance (nmr), nuclear overhauser effects
(noe), protein-ligand interaction, relaxation time, std (saturation transfer
difference), trosy (transverse relaxation optimized spectroscopy), waterlogsy
(water-ligand observed via Gradient Spectroscopy).
