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In silico investigation of a novel anti-EGFR scFv-IL-24 fusion protein induces apoptosis in malignant cells

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Abstract

Context

Epidermal growth factor receptor (EGFR), a member of the HER receptor family, is over expressed in various cancer cells. Using tumor-specific antibodies to deliver cytotoxic agents directly to the tumor cells is an effective treatment strategy. Targeted therapy by fusing anti-EGFR scFv with tumor-specific cytokines promises the emergence of a new era.

Methods

We designed a novel immuno-apoptotic fusion protein, anti-EGFR scFv-IL-24, consisting of a specific cancer cell targeting antibody and recombinant cytokine IL-24 to explore its anti-cancerous potential. Amino acid sequences of both anti-EGFR scFv and IL-24 were fused using a specific rigid linker. In silico characterization of the designed fusion protein like to predict the primary, secondary, physiochemical properties, quality, and structural validation using online bioinformatic tools. The newly designed fusion protein consists of 402 amino acids that showed good quality with a predicted value of 76.7% having 81.5% residues in the most favored region as predicted by ERRAT2 and Ramachandran plot analysis. Docking and simulation studies were performed using HDOCK and Desmond module of Schrodinger. All the parameters of quality, validity, interaction analysis, and stability suggested that the fused molecule is fully operational and functional. The results of the study support that the anti-EGFR scFv-IL-24 fused protein could be proved as a novel candidate to combat cancer.

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Funding

This work was supported in part by grants from the HEC Pakistan under NRPU 2021 (Project No. 16935) and the University of the Punjab Lahore Pakistan.

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Authors and Affiliations

  1. Centre for Applied Molecular Biology, University of the Punjab, 87-West Canal, Bank Road, Lahore, 53700, Pakistan

    Zaroon, Shakira Aslam, Shahnila Qureshi & Hamid Bashir

  2. Department of Bioscience, COMSAT University Islamabad, Islamabad, Pakistan

    Numan yousaf

Authors
  1. Zaroon
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  2. Numan yousaf
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  3. Shakira Aslam
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  4. Shahnila Qureshi
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  5. Hamid Bashir
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Contributions

Methodology, formal analysis, validation: Z, H.B, N.Y; investigation resources: S.A; data curation: S.Q, Z, N.Y; and original draft preparation: Z, H.B, N.Y, S.A, S.Q. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Hamid Bashir.

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Zaroon, yousaf, N., Aslam, S. et al. In silico investigation of a novel anti-EGFR scFv-IL-24 fusion protein induces apoptosis in malignant cells. J Mol Model 29, 282 (2023). https://doi.org/10.1007/s00894-023-05690-6

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