NMR spectroscopy is the most versatile technique for the investigation of
structural and dynamic aspects of biological molecules and their interactions in solution.
In addition, recent advances in the NMR instrumentation and methodology have
allowed to overcome problems relating to macromolecule size and have made NMR a
very feasible technique also for the investigation of highly dynamic, partially
inhomogeneous molecules and heterogeneous complexes.
NMR has been widely employed to study molecular interactions that take place between
biomacromolecules and their ligands at different levels of complexity. The
characterization of the fine structural details of the recognition processes is essential to
understand fundamental mechanisms underlying phenomena of biological and
biomedical relevance and can be exploited for the rational design of new therapeutic
and diagnostic strategies. In fact, ligands can be represented both by macromolecules,
such as other proteins, nucleic acids or lipids, and small molecules (MW less than 1000
kDa), such as allosteric effectors, cofactors, substrates and their analogues, drugs.
Depending on the complex features, the interaction strength and the chemical nature of
the interacting species, different experimental approaches can be chosen.
In this chapter we will describe the most important NMR techniques developed to study
molecular recognition processes involving proteins and nucleic acids also focusing on
their application to drug discovery and development. The most significant examples
provided in literature will be also reported in details.
Keywords: Diffusion filtering, drug design, drug discovery, ILOE, isotope
filtering, ligand identification, ligand optimization, ligand screening, ligandreceptor
interaction studies, molecular recognition processes, NMR spectroscopy,
NOE pumping, relaxation filtering, SAR by NMR, STD-NMR, structural biology,
target identification, target validation, trNOESY, WaterLOGSY.