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Discovery of novel targets and mechanisms of MEK inhibitor Selumetinib for LGG treatment based on molecular docking and molecular dynamics simulation

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Abstract

Based on molecular docking and molecular dynamics simulation, to find a new target and mechanism of MEK inhibitor Selumetinib in the treatment of low-grade glioma (LGG), and to provide theoretical guidance for its clinical medication. All possible targets of Selumetinib were fished through the compound target prediction database. New targets of Selumetinib in the treatment of LGG were found and its mechanism was evaluated employing molecular docking, gene difference analysis, molecular dynamics simulation, and protein subcellular localization prediction. A total of 100 Selumetinib targets and 85 LGG-related targets were screened in this study. There were 7 active targets at the intersection of the two. Through protein interaction (PPI), gene enrichment analysis, and gene difference analysis, one effective target of Selumetinib was finally screened, CDK2 mainly existing in the cytoplasm, endoplasmic reticulum, and plasma membrane; the target plays a role in the treatment of LGG by inhibiting the signal pathways of PI3K Akt and participating in biological processes such as peptide amino acid modification, regulation of intracellular signal transduction, and positive regulation of cell metabolism. CDK2 may be a new direction of Selumetinib in the clinical treatment of LGG.

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Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due the limited scope of data availability; these data are used under the license of this study and are not disclosed, but are available from the author (sedate@stu.shzu.edu.cn (Dongdong Zhang)) on reasonable request.

We confirm that all methods in the manuscript are carried out in accordance with the relevant guidelines.

Abbreviations

GBM:

Glioblastoma

LGG:

Low-grade glioma

PD-1:

Programmed cell death-1

PDL-1:

Programmed cell death-ligand 1

NF1:

Neurofibromas 1

PN:

Plexiform neurofibroma

BP:

Biology progress

KEGG:

Kyoto Encyclopedia of Genes and Genomes

PPI:

Protein-protein interaction

MD:

Molecule dynamics

RMSD:

Root mean squared error

RMSF:

Root mean square float

GDA:

Human Genetic Disease Association

k-NN:

K-nearest neighbor

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Funding

“Shihezi University high-level talent scientific research start-up project” prevention and control of recombinant endophytes

“Technical research on” branch blight “of fragrant pear,” Project No.: RCZK202047

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Author notes

  1. Dongdong Zhang and Tieying Zhang are contributed equally to this research.

Authors and Affiliations

  1. School of Life Sciences, Shihezi University, Xiangyang Street, Xinjiang, China

    Dongdong Zhang, Tieying Zhang, Jianbo Zhu & Jin Li

Authors
  1. Dongdong Zhang
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  2. Tieying Zhang
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  3. Jianbo Zhu
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  4. Jin Li
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Contributions

Dongdong Zhang and Tieying Zhang contributed equally to this research and Dongdong Zhang and Tieying Zhang wrote the main manuscript text. Jin Li and Jianbo Zhu are the corresponding authors. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Jianbo Zhu or Jin Li.

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The authors declare no competing interests.

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Zhang, D., Zhang, T., Zhu, J. et al. Discovery of novel targets and mechanisms of MEK inhibitor Selumetinib for LGG treatment based on molecular docking and molecular dynamics simulation. J Mol Model 28, 138 (2022). https://doi.org/10.1007/s00894-022-05132-9

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  • DOI: https://doi.org/10.1007/s00894-022-05132-9

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