In silico Analysis of Anti-cervical Cancer Drug Off-Target Effects on Diverse Protein Isoforms for Enhanced Therapeutic Strategies

Authors

  • Azhar Iqbal Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan https://orcid.org/0000-0001-7830-0685
  • Faisal Ali Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Shanza Choudhary Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Adiba Qayyum Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Fiza Arshad Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Sara Ashraf Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Moawaz Aziz Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Asad Ullah Shakil Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Momina Hussain Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Muhammad Sajid Faculty of Life Sciences, Department of Biotechnology, University of Okara, Pakistan
  • Sheikh Arslan Sehgal Department of Bioinformatics, Islamia University Bahawalpur, Pakistan

DOI:

https://doi.org/10.20535/ibb.2023.7.4.288017

Keywords:

cervical cancer, isoforms, molecular docking, interaction analysis, bioinformatics approaches

Abstract

Background. Cervical cancer is a serious medical condition that affects hundreds of thousands of individuals worldwide annually. The selection and analysis of suitable gene targets in the early stages of drug design are crucial for combating this disease. However, overlooking the presence of various protein isoforms may result in unwanted therapeutic or harmful side effects.

Objective. This study aimed to provide a computational analysis of the interactions between cervical cancer drugs and their targets, influenced by alternative splicing.

Methods. Using open-access databases, we targeted 45 FDA-approved cervical cancer drugs that target various genes having more than two distinct protein-coding isoforms. To check the conservation of binding pocket in isoforms of the genes, multiple sequence analysis was performed. To better understand the associations between proteins and FDA-approved drugs at the isoform level, we conducted molecular docking analysis.

Results. The study reveals that many drugs lack potential targets at the isoform level. Further examination of various isoforms of the same gene revealed distinct ligand-binding pocket configurations, including differences in size, shape, electrostatic characteristics, and structure.

Conclusions. This study highlights the potential risks of focusing solely on the canonical isoform, and ignoring the impact of cervical cancer drugs on- and off-target effects at the isoform level. These findings emphasize the importance of considering interactions between drugs and their targets at the isoform level to promote effective treatment outcomes.

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Published

2023-12-05

How to Cite

1.
Iqbal A, Ali F, Choudhary S, Qayyum A, Arshad F, Ashraf S, Aziz M, Ullah Shakil A, Hussain M, Sajid M, Arslan Sehgal S. In silico Analysis of Anti-cervical Cancer Drug Off-Target Effects on Diverse Protein Isoforms for Enhanced Therapeutic Strategies. Innov Biosyst Bioeng [Internet]. 2023Dec.5 [cited 2024May20];7(4):36-47. Available from: http://ibb.kpi.ua/article/view/288017

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Vol. 7 No. 4 (2023)

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