Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.

Flavonoids, a class of natural compounds with variable phenolic structures, have been found to possess anti-cancer activities by modulating different enzymes and receptors like CDK6. To understand the binding behavior of flavonoids that inhibit the active CDK6, molecular dynamics (MD) simulations we...

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Main Authors: Jingxiao Zhang, Lilei Zhang, Yangcheng Xu, Shanshan Jiang, Yueyue Shao
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5929560?pdf=render
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author Jingxiao Zhang
Lilei Zhang
Yangcheng Xu
Shanshan Jiang
Yueyue Shao
author_facet Jingxiao Zhang
Lilei Zhang
Yangcheng Xu
Shanshan Jiang
Yueyue Shao
author_sort Jingxiao Zhang
collection DOAJ
description Flavonoids, a class of natural compounds with variable phenolic structures, have been found to possess anti-cancer activities by modulating different enzymes and receptors like CDK6. To understand the binding behavior of flavonoids that inhibit the active CDK6, molecular dynamics (MD) simulations were performed on six inhibitors, chrysin (M01), fisetin (M03), galangin (M04), genistein (M05), quercetin (M06) and kaempferol (M07), complexed with CDK6/cyclin D. For all six flavonoids, the 3'-OH and 4'-OH of B-ring were found to be favorable for hydrogen bond formation, but the 3-OH on the C-ring and 5-OH on the A-ring were unfavorable, which were confirmed by the MD simulation results of the test molecule, 3', 4', 7-trihydroxyflavone (M15). The binding efficiencies of flavonoids against the CDK6/cyclin D complex were mainly through the electrostatic (especially the H-bond force) and vdW interactions with residues ILE19, VAL27, ALA41, GLU61, PHE98, GLN103, ASP163 and LEU152. The order of binding affinities of these flavonoids toward the CDK6/cyclin D was M03 > M01 > M07 > M15 > M06 > M05 > M04. It is anticipated that the binding features of flavonoid inhibitors studied in the present work may provide valuable insights for the development of CDK6 inhibitors.
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spelling doaj.art-770f715d44fd4558a586c688eaca30372022-12-21T17:33:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01135e019665110.1371/journal.pone.0196651Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.Jingxiao ZhangLilei ZhangYangcheng XuShanshan JiangYueyue ShaoFlavonoids, a class of natural compounds with variable phenolic structures, have been found to possess anti-cancer activities by modulating different enzymes and receptors like CDK6. To understand the binding behavior of flavonoids that inhibit the active CDK6, molecular dynamics (MD) simulations were performed on six inhibitors, chrysin (M01), fisetin (M03), galangin (M04), genistein (M05), quercetin (M06) and kaempferol (M07), complexed with CDK6/cyclin D. For all six flavonoids, the 3'-OH and 4'-OH of B-ring were found to be favorable for hydrogen bond formation, but the 3-OH on the C-ring and 5-OH on the A-ring were unfavorable, which were confirmed by the MD simulation results of the test molecule, 3', 4', 7-trihydroxyflavone (M15). The binding efficiencies of flavonoids against the CDK6/cyclin D complex were mainly through the electrostatic (especially the H-bond force) and vdW interactions with residues ILE19, VAL27, ALA41, GLU61, PHE98, GLN103, ASP163 and LEU152. The order of binding affinities of these flavonoids toward the CDK6/cyclin D was M03 > M01 > M07 > M15 > M06 > M05 > M04. It is anticipated that the binding features of flavonoid inhibitors studied in the present work may provide valuable insights for the development of CDK6 inhibitors.http://europepmc.org/articles/PMC5929560?pdf=render
spellingShingle Jingxiao Zhang
Lilei Zhang
Yangcheng Xu
Shanshan Jiang
Yueyue Shao
Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.
PLoS ONE
title Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.
title_full Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.
title_fullStr Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.
title_full_unstemmed Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.
title_short Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex.
title_sort deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6 cyclin d complex
url http://europepmc.org/articles/PMC5929560?pdf=render
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AT yangchengxu decipheringthebindingbehaviorofflavonoidstothecyclindependentkinase6cyclindcomplex
AT shanshanjiang decipheringthebindingbehaviorofflavonoidstothecyclindependentkinase6cyclindcomplex
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