Binding site identification and structure determination of protein-ligand complexes by NMR a semiautomated approach.

摘要: Over the last 15 years, role of NMR spectroscopy in lead identification and optimization stages pharmaceutical drug discovery has steadily increased. occupies a unique niche biophysical analysis drug-like compounds because its ability to identify binding sites, affinities, ligand poses at level individual amino acids without necessarily solving structure protein-ligand complex. However, it can also provide structures flexible proteins low-affinity (K(d)>10(-6)M) complexes, which often fail crystallize. This chapter emphasizes throughput-focused protocol that aims practical aspects site characterization, automated semiautomated assignment methods, determination complexes by NMR.