Background:
NMR spectroscopy is one of the most powerful tools to study the structure and interaction properties of peptides and proteins from a dynamic perspective. Knowing the bioactive conformations of peptides is crucial in the
drug discovery field to design more efficient analogue ligands and inhibitors of protein-protein interactions targeting therapeutically relevant systems.
Objective:
This review provides a toolkit to investigate peptide conformational properties by NMR. Methods: Articles cited
herein, related to NMR studies of peptides and proteins were mainly searched through Pubmed and the web. More recent
and old books on NMR spectroscopy written by eminent scientists in the field were consulted as well.
Results:
The review is mainly focused on NMR tools to gain the 3D structure of small unlabeled peptides. It is more application-oriented as it is beyond its goal to deliver a profound theoretical background. However, the basic principles of 2D
homonuclear and heteronuclear experiments are briefly described. Protocols to obtain isotopically labeled peptides and principal triple resonance experiments needed to study them, are discussed as well.
Conclusion:
NMR is a leading technique in the study of conformational preferences of small flexible peptides whose structure can be often only described by an ensemble of conformations. Although NMR studies of peptides can be easily and fast
performed by canonical protocols established a few decades ago, more recently we have assisted to tremendous improvements of NMR spectroscopy to investigate instead large systems and overcome its molecular weight limit.
As one of the few analytical methods that offer atomic resolution, NMR spectroscopy is a valuable tool to study the interaction of proteins with their interaction partners, both biomolecules and synthetic ligands. In recent years, the focus in chemistry has kept expanding from targeting small binding pockets in proteins to recognizing patches on protein surfaces, mostly via supramolecular chemistry, with the goal to modulate protein–protein interactions. Here we present NMR methods that have been applied to characterize these molecular interactions and discuss the challenges of this endeavor.
Using Singular Value Decomposition to Characterize Protein-Protein Interactions by In-cell NMR Spectroscopy
