Chemistry Reference
In-Depth Information
Application of NMR and Molecular Docking
in Structure-Based Drug Discovery
Jaime L. Stark and Robert Powers
Abstract Drug discovery is a complex and costly endeavor, where few drugs that
reach the clinical testing phase make it to market. High-throughput screening (HTS)
is the primary method used by the pharmaceutical industry to identify initial lead
compounds. Unfortunately, HTS has a high failure rate and is not particularly
efficient at identifying viable drug leads. These shortcomings have encouraged
the development of alternative methods to drive the drug discovery process.
Specifically, nuclear magnetic resonance (NMR) spectroscopy and molecular
docking are routinely being employed as important components of drug discovery
research. Molecular docking provides an extremely rapid way to evaluate likely
binders from a large chemical library with minimal cost. NMR ligand-affinity
screens can directly detect a protein-ligand interaction, can measure a
corresponding dissociation constant, and can reliably identify the ligand binding
site and generate a co-structure. Furthermore, NMR ligand affinity screens and
molecular docking are perfectly complementary techniques, where the combination
of the two has the potential to improve the efficiency and success rate of drug
discovery. This review will highlight the use of NMR ligand affinity screens and
molecular docking in drug discovery and describe recent examples where the two
techniques were combined to identify new and effective therapeutic drugs.
Keywords Drug discovery, FAST-NMR,
In silico
screening, Ligand affinity
screens, Molecular docking, Nuclear magnetic resonance, Virtual screening
