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

doi:10.1016/j.jmgm.2017.02.014

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 journal › Article › peer-review

18 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 language	English
Pages (from-to)	54-60
Number of pages	7
Journal	Journal of Molecular Graphics and Modelling
Volume	74
DOIs	https://doi.org/10.1016/j.jmgm.2017.02.014
State	Published - Jun 1 2017

Bibliographical note

Publisher Copyright:
© 2017

Funding

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

Funders	Funder number
National Institutes of Health (NIH)
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	R01GM057513
American Lebanese Syrian Associated Charities

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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

Access to Document

10.1016/j.jmgm.2017.02.014

Cite this

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

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.",

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language = "English",

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AU - Bharatham, Nagakumar

AU - Finch, Kristin E.

AU - Min, Jaeki

AU - Mayasundari, Anand

AU - Dyer, Michael A.

AU - Guy, R. Kiplin

AU - Bashford, Donald

PY - 2017/6/1

Y1 - 2017/6/1

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AB - 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.

KW - Docking

KW - Fluorescence polarization

KW - Mdm4

KW - Mdmx

KW - Molecular dynamics simulations

KW - Nutlin

KW - Virtual screening

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ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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