Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations

p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fise...

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Autores principales: Verma, Sharad, Grover, Sonam, Tyagi, Chetna, Goyal, Sukriti, Jamal, Salma, Singh, Aditi, Grover, Abhinav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749206/
https://www.ncbi.nlm.nih.gov/pubmed/26863418
http://dx.doi.org/10.1371/journal.pone.0149014
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author Verma, Sharad
Grover, Sonam
Tyagi, Chetna
Goyal, Sukriti
Jamal, Salma
Singh, Aditi
Grover, Abhinav
author_facet Verma, Sharad
Grover, Sonam
Tyagi, Chetna
Goyal, Sukriti
Jamal, Salma
Singh, Aditi
Grover, Abhinav
author_sort Verma, Sharad
collection PubMed
description p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fisetin, Galangin and Luteolin) by MD simulation and MM/PBSA free energy calculations. All polyphenols bind to hydrophobic groove of MDM2 and the binding was found to be stable throughout MD simulation. Luteolin showed the highest negative binding free energy value of -173.80 kJ/mol followed by Fisetin with value of -172.25 kJ/mol. It was found by free energy calculations, that hydrophobic interactions (vdW energy) have major contribution in binding free energy.
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spelling pubmed-47492062016-02-26 Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations Verma, Sharad Grover, Sonam Tyagi, Chetna Goyal, Sukriti Jamal, Salma Singh, Aditi Grover, Abhinav PLoS One Research Article p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fisetin, Galangin and Luteolin) by MD simulation and MM/PBSA free energy calculations. All polyphenols bind to hydrophobic groove of MDM2 and the binding was found to be stable throughout MD simulation. Luteolin showed the highest negative binding free energy value of -173.80 kJ/mol followed by Fisetin with value of -172.25 kJ/mol. It was found by free energy calculations, that hydrophobic interactions (vdW energy) have major contribution in binding free energy. Public Library of Science 2016-02-10 /pmc/articles/PMC4749206/ /pubmed/26863418 http://dx.doi.org/10.1371/journal.pone.0149014 Text en © 2016 Verma et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Verma, Sharad
Grover, Sonam
Tyagi, Chetna
Goyal, Sukriti
Jamal, Salma
Singh, Aditi
Grover, Abhinav
Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations
title Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations
title_full Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations
title_fullStr Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations
title_full_unstemmed Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations
title_short Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations
title_sort hydrophobic interactions are a key to mdm2 inhibition by polyphenols as revealed by molecular dynamics simulations and mm/pbsa free energy calculations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749206/
https://www.ncbi.nlm.nih.gov/pubmed/26863418
http://dx.doi.org/10.1371/journal.pone.0149014
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