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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2016
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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. |
format | Online Article Text |
id | pubmed-4749206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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