Application of NMR and molecular docking in structure-based drug discovery

Jaime L. Stark, Robert Powers

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-34
Number of pages34
JournalTopics in Current Chemistry
Volume326
DOIs
StatePublished - 2012

Fingerprint

Nuclear magnetic resonance
Ligands
Pharmaceutical Preparations
Screening
Throughput
Lead compounds
Nuclear magnetic resonance spectroscopy
Binders
Binding Sites
Drug Discovery
Testing
Costs
Industry
Proteins

Keywords

  • Drug discovery
  • FAST-NMR
  • In silico screening
  • Ligand affinity screens
  • Molecular docking
  • Nuclear magnetic resonance
  • Virtual screening

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Application of NMR and molecular docking in structure-based drug discovery. / Stark, Jaime L.; Powers, Robert.

In: Topics in Current Chemistry, Vol. 326, 2012, p. 1-34.

Research output: Contribution to journalArticle

@article{26950b2159454b22940c7b2059239bc2,
title = "Application of NMR and molecular docking in structure-based drug discovery",
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",
author = "Stark, {Jaime L.} and Robert Powers",
year = "2012",
doi = "10.1007/128_2011_213",
language = "English (US)",
volume = "326",
pages = "1--34",
journal = "Topics in Current Chemistry",
issn = "0340-1022",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Application of NMR and molecular docking in structure-based drug discovery

AU - Stark, Jaime L.

AU - Powers, Robert

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Drug discovery

KW - FAST-NMR

KW - In silico screening

KW - Ligand affinity screens

KW - Molecular docking

KW - Nuclear magnetic resonance

KW - Virtual screening

UR - http://www.scopus.com/inward/record.url?scp=84859922833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859922833&partnerID=8YFLogxK

U2 - 10.1007/128_2011_213

DO - 10.1007/128_2011_213

M3 - Article

VL - 326

SP - 1

EP - 34

JO - Topics in Current Chemistry

JF - Topics in Current Chemistry

SN - 0340-1022

ER -