On the Applicability of Elastic Network Normal Modes in Small-Molecule Docking

Publication type:
Journal article
Metadata:
Autoren
  • Matthias Dietzen
  • Elena Zotenko
  • Andreas Hildebrandt
  • Thomas Lengauer
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000301884400019&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1021/ci2004847
eISSN
1549-960X
Externe Identifier
  • Clarivate Analytics Document Solution ID: 913NJ
  • PubMed Identifier: 22320151
ISSN
1549-9596
Ausgabe der Veröffentlichung
3
Zeitschrift
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Paginierung
844 - 856
Datum der Veröffentlichung
2012
Status
Published
Titel
On the Applicability of Elastic Network Normal Modes in Small-Molecule Docking
Sub types
  • Article
Ausgabe der Zeitschrift
52

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Matthias Dietzen
  • Elena Zotenko
  • Andreas Hildebrandt
  • Thomas Lengauer
DOI
10.1021/ci2004847
eISSN
1549-960X
ISSN
1549-9596
Ausgabe der Veröffentlichung
3
Zeitschrift
Journal of Chemical Information and Modeling
Sprache
en
Online publication date
2012
Paginierung
844 - 856
Datum der Veröffentlichung
2012
Status
Published
Herausgeber
American Chemical Society (ACS)
Herausgeber URL
http://dx.doi.org/10.1021/ci2004847
Datum der Datenerfassung
2023
Titel
On the Applicability of Elastic Network Normal Modes in Small-Molecule Docking
Ausgabe der Zeitschrift
52

Data source: Crossref

Abstract
Incorporating backbone flexibility into protein-ligand docking is still a challenging problem. In protein-protein docking, normal mode analysis (NMA) has become increasingly popular as it can be used to describe the collective motions of a biological system, but the question of whether NMA can also be useful in predicting the conformational changes observed upon small-molecule binding has only been addressed in a few case studies. Here, we describe a large-scale study on the applicability of NMA for protein-ligand docking using 433 apo/holo pairs of the Astex data sets. On the basis of sets of the first normal modes from the apo structure, we first generated for each paired holo structure a set of conformations that optimally reproduce its C(α) trace with respect to the underlying normal mode subspace. Using AutoDock, GOLD, and FlexX we then docked the original ligands into these conformations to assess how the docking performance depends on the number of modes used to reproduce the holo structure. The results of our study indicate that, even for such a best-case scenario, the use of normal mode analysis in small-molecule docking is restricted and that a general rule on how many modes to use does not seem to exist or at least is not easy to find.
Addresses
  • Max-Planck-Institut für Informatik, 66123 Saarbrücken, Germany. mdietzen@mpi-inf.mpg.de
Autoren
  • Matthias Dietzen
  • Elena Zotenko
  • Andreas Hildebrandt
  • Thomas Lengauer
DOI
10.1021/ci2004847
eISSN
1549-960X
Externe Identifier
  • PubMed Identifier: 22320151
Open access
false
ISSN
1549-9596
Ausgabe der Veröffentlichung
3
Zeitschrift
Journal of chemical information and modeling
Schlüsselwörter
  • Apoproteins
  • Protein Conformation
  • Elasticity
  • Models, Molecular
  • Small Molecule Libraries
Sprache
eng
Medium
Print-Electronic
Online publication date
2012
Paginierung
844 - 856
Datum der Veröffentlichung
2012
Status
Published
Datum der Datenerfassung
2012
Titel
On the applicability of elastic network normal modes in small-molecule docking.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
52

Data source: Europe PubMed Central

Abstract
Incorporating backbone flexibility into protein-ligand docking is still a challenging problem. In protein-protein docking, normal mode analysis (NMA) has become increasingly popular as it can be used to describe the collective motions of a biological system, but the question of whether NMA can also be useful in predicting the conformational changes observed upon small-molecule binding has only been addressed in a few case studies. Here, we describe a large-scale study on the applicability of NMA for protein-ligand docking using 433 apo/holo pairs of the Astex data sets. On the basis of sets of the first normal modes from the apo structure, we first generated for each paired holo structure a set of conformations that optimally reproduce its C(α) trace with respect to the underlying normal mode subspace. Using AutoDock, GOLD, and FlexX we then docked the original ligands into these conformations to assess how the docking performance depends on the number of modes used to reproduce the holo structure. The results of our study indicate that, even for such a best-case scenario, the use of normal mode analysis in small-molecule docking is restricted and that a general rule on how many modes to use does not seem to exist or at least is not easy to find.
Autoren
  • Matthias Dietzen
  • Elena Zotenko
  • Andreas Hildebrandt
  • Thomas Lengauer
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/22320151
DOI
10.1021/ci2004847
eISSN
1549-960X
Ausgabe der Veröffentlichung
3
Zeitschrift
J Chem Inf Model
Schlüsselwörter
  • Apoproteins
  • Elasticity
  • Models, Molecular
  • Protein Conformation
  • Small Molecule Libraries
Sprache
eng
Country
United States
Paginierung
844 - 856
Datum der Veröffentlichung
2012
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2012
Titel
On the applicability of elastic network normal modes in small-molecule docking.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
52

Data source: PubMed

Autoren
  • Matthias Dietzen
  • Elena Zotenko
  • Andreas Hildebrandt
  • Thomas Lengauer
Zeitschrift
Journal of chemical information and modeling
Artikelnummer
3
Paginierung
844 - 856
Datum der Veröffentlichung
2012
Herausgeber
ACS Publications
Datum der Datenerfassung
2020
Titel
On the Applicability of Elastic Network Normal Modes in Small-Molecule Docking
Sub types
  • article
Ausgabe der Zeitschrift
52

Data source: Manual

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