Structural and Dynamic Information on Ligand Binding

Abstract

The function of the vast majority of proteins in the cell depends upon their noncovalent interactions with other molecules, ranging from enzyme-substrate interactions to the array of protein-protein and protein-nucleic acid interactions involved in, for example, the regulation of transcription. NMR has proved very valuable in the study of the interaction of proteins with both small and large molecules. In this chapter the focus will be on the basic principles of the study of ligand binding by NMR and on applications to small moleculeprotein interactions. Studies of macromolecular complexes are covered in Chapter 8. The use of NMR to study protein-ligand interactions is a vast area and, for reasons of space, many of the references herein are to reviews rather than to original papers; my apologies to those whose important contributions have not been cited directly.NMR can of course provide information on the structure of protein-ligand complexes, just as it can on the structure of the protein itself. However, the NMR spectrum is sensitive to both the equilibrium and the kinetics of the binding process. These effects can provide valuable information in themselves but, most importantly, they must be understood in order to interpret the spectrum correctly.

Deconvolution of Complex 1D NMR Spectra Using Objective Model Selection

“…τ p and τ p* ) resulting in different equilibrium populations in each environment and overall exchange rate (e.g. k ex = 1/τ p + 1/τ p* ) [ 12 ].…”