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J Mol Graph Model. 2017 Jun;74:54-60. doi: 10.1016/j.jmgm.2017.02.014. Epub 2017 Feb 24.

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

Author information

1
Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address: nagakumarb@ccamp.res.in.
2
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
3
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
4
Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address: donbashford@outlook.com.

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.

KEYWORDS:

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

PMID:
28351017
PMCID:
PMC5508530
DOI:
10.1016/j.jmgm.2017.02.014
[Indexed for MEDLINE]
Free PMC Article

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