Molecular Dynamics Simulation of the Interaction of Saccharin with Human p53 Protein

Shahlaei , M; Mansourian , M

doi:10.61186/armaghanj.28.6.11

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Volume 28, Issue 6 (12-2023)

__Armaghane Danesh__ 2023, 28(6): 815-837

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Molecular Dynamics Simulation of the Interaction of Saccharin with Human p53 Protein

M Shahlaei¹

, M Mansourian

1- Department of Medicinal Chemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran,
2- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran , mahboubehmansourian90@gmail.com

Abstract: (471 Views)

Background & aim: The role of artificial sweeteners in the occurrence of cancer risk has been widely discussed during the last few decades. Therefore, the aim of the present study was to determine the dynamic and molecular simulation of the interaction of saccharin(SA) with human p53 protein.

Methods: The present bioinformatics study was conducted in 2023. The interaction of SA and sodium saccharin (SSA) with the human p53 gene promoter (Pp53g) has already been published in 2019 in two theoretical and experimental sections. But in the present study, the binding ability and the binding site of SA ligand as a synthetic sweetener with human p53 protein (receptor) as a tumor suppressor was theoretically performed. The amino acid residues involved in the interaction, energy free binding and binding constant were determined. Molecular docking was used for molecular interaction calculations. More detailed information about the binding method of the ligand-receptor complex was obtained by molecular dynamics (MD) simulation. The structure and topology file for the human p53 protein extracted from the protein database was created based on the AMBER 99 force field with the GROMACS 5.3.1 program. Acpype/Antechamber program with General AMBER Force Field (GAFF) was used to create structure file and ligand topology in MD simulation. This force field was compatible with the AMBER 99 force field. The simulation time in explicit solvent was 50 ns for SA-p53 protein complex. The collected data were analyzed using different software and compared with the results of related articles.

Results: The results of molecular docking indicated that the SA compound was bound to human p53 protein with a binding energy of -4.55 kcal/mol and a binding constant of 462.18 μM. A hydrogen bond was formed between SA and amino acid Leu137. The conformational changes resulting from MD simulation for the ligand-protein complex showed that SA can bind to Arg196 and His179 as key amino acids of p53 protein in the DNA binding region through two hydrogen bonds. SA can also be placed in the adjacent of amino acids Leu137, Ala138, His179, Asp184 and Met237 through hydrophobic bonds. The values of the plots of root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg) for free p53 protein and in the presence of SA ligand show the stable binding of SA to p53 protein.

Conclusion: The present study could provide valuable information about the binding mechanism of SA to human p53 protein as a macromolecule at the molecular level with subatomic details. The results can be useful in determining the potential carcinogenic risk of this sweetener due to its high consumption and the design and synthesis of newer and safer artificial sweeteners.

Keywords: Saccharin, Human p53 protein, Molecular docking, Molecular dynamics simulation, Cancer

Full-Text [PDF 925 kb] (85 Downloads)

Type of Study: Research | Subject: Special
Received: 2023/09/11 | Accepted: 2023/11/16 | Published: 2023/12/9

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Shahlaei M, Mansourian M. Molecular Dynamics Simulation of the Interaction of Saccharin with Human p53 Protein. armaghanj 2023; 28 (6) :815-837
URL: http://armaghanj.yums.ac.ir/article-1-3517-en.html

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