Performance of a docking/molecular dynamics protocol for virtual screening of nutlin-class inhibitors of Mdmx

Nagakumar Bharatham, Kristin E. Finch, Jaeki Min, Anand Mayasundari, Michael A. Dyer, R. Kiplin Guy, Donald Bashford

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

A virtual screening protocol involving docking and molecular dynamics has been tested against the results of fluorescence polarization assays testing the potency of a series of compounds of the nutlin class for inhibition of the interaction between p53 and Mdmx, an interaction identified as a driver of certain cancers. The protocol uses a standard docking method (AutoDock) with a cutoff based on the AutoDock score (ADscore), followed by molecular dynamics simulation with a cutoff based on root-mean-square-deviation (RMSD) from the docked pose. An analysis of the experimental and computational results shows modest performance of ADscore alone, but dramatically improved performance when RMSD is also used.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalJournal of Molecular Graphics and Modelling
Volume74
DOIs
StatePublished - Jun 1 2017

Bibliographical note

Funding Information:
We acknowledge support from the American Lebanese-Syrian Associated Charities (ALSAC). DB and NB acknowledge support from the National Institutes of Health (GM57513).

Publisher Copyright:
© 2017

Keywords

  • Docking
  • Fluorescence polarization
  • Mdm4
  • Mdmx
  • Molecular dynamics simulations
  • Nutlin
  • Virtual screening

ASJC Scopus subject areas

  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Materials Chemistry

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