Faculty Collaboration Database

Binding site identification and structure determination of protein-ligand complexes by NMR a semiautomated approach. Methods Enzymol 2011;493:241-75

Date

03/05/2011

Pubmed ID

21371594

Pubmed Central ID

PMC3635485

DOI

10.1016/B978-0-12-381274-2.00010-8

Scopus ID

2-s2.0-79952366609   42 Citations

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 protein-ligand 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 protein-ligand complexes by NMR.

Author List

Ziarek JJ, Peterson FC, Lytle BL, Volkman BF

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Automation, Laboratory
Binding Sites
Drug Design
Drug Discovery
Hydrogen Bonding
Ligands
Magnetic Resonance Spectroscopy
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Proteins
Software