TY - CHAP
T1 - Binding Site Identification and Structure Determination of ProteinLigand Complexes by NMR
T2 - A Semiautomated Approach
AU - Ziarek, Joshua J.
AU - Peterson, Francis C.
AU - Lytle, Betsy L.
AU - Volkman, Brian F.
PY - 2011
Y1 - 2011
N2 - Abstract Over the last 15 years, the role of NMR spectroscopy in the lead identification and optimization stages of pharmaceutical drug discovery has steadily increased. NMR occupies a unique niche in the biophysical analysis of drug-like compounds because of its ability to identify binding sites, affinities, and ligand poses at the level of individual amino acids without necessarily solving the structure of the proteinligand complex. However, it can also provide structures of flexible proteins and low-affinity (K d > 10 - 6 M) complexes, which often fail to crystallize. This chapter emphasizes a throughput-focused protocol that aims to identify practical aspects of binding site characterization, automated and semiautomated NMR assignment methods, and structure determination of proteinligand complexes by NMR.
AB - Abstract Over the last 15 years, the role of NMR spectroscopy in the lead identification and optimization stages of pharmaceutical drug discovery has steadily increased. NMR occupies a unique niche in the biophysical analysis of drug-like compounds because of its ability to identify binding sites, affinities, and ligand poses at the level of individual amino acids without necessarily solving the structure of the proteinligand complex. However, it can also provide structures of flexible proteins and low-affinity (K d > 10 - 6 M) complexes, which often fail to crystallize. This chapter emphasizes a throughput-focused protocol that aims to identify practical aspects of binding site characterization, automated and semiautomated NMR assignment methods, and structure determination of proteinligand complexes by NMR.
UR - http://www.scopus.com/inward/record.url?scp=79952366609&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952366609&partnerID=8YFLogxK
U2 - 10.1016/B978-0-12-381274-2.00010-8
DO - 10.1016/B978-0-12-381274-2.00010-8
M3 - Chapter
C2 - 21371594
AN - SCOPUS:79952366609
T3 - Methods in Enzymology
SP - 241
EP - 275
BT - Methods in Enzymology
PB - Academic Press Inc
ER -