title: Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations.
abstract: 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.
authors: School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors: Sharad
authors: S
authors: Verma
authors: Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India.
authors: Sonam
authors: S
authors: Grover
authors: School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors: Chetna
authors: C
authors: Tyagi
authors: Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan, India.
authors: Sukriti
authors: S
authors: Goyal
authors: Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan, India.
authors: Salma
authors: S
authors: Jamal
authors: Department of Biotechnology, TERI University, Vasant Kunj, New Delhi, India.
authors: Aditi
authors: A
authors: Singh
authors: School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors: Abhinav
authors: A
authors: Grover
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D047310:Apigenin / Q000737:chemistry; D003198:Computer Simulation; D004260:DNA Repair; D005419:Flavonoids / Q000737:chemistry; D044948:Flavonols; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047311:Luteolin / Q000737:chemistry; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D059808:Polyphenols / Q000737:chemistry*; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors*; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D044948:Flavonols; D059808:Polyphenols; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C037032:galangin; D047310:Apigenin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D047311:Luteolin; C017875:fisetin