Computational Analysis of Post-Translational Modifications in Diabetes: A Systems Biology and Structure-Based Drug Discovery Approach

• Ahmed S Elfaki

  Biotechnology Department, Faculty of Science, Cairo University, Cairo, Egypt

  Author

• Lobna Badr

  YS-G1004 Lab Department Of Cheminformatics EBO Bio Solution London United Kingdom

  Author

• Abdelrahman Mohamed Youseff Mohamed

  Faculty of Science, Alexandria University, Alexandria, Egypt

  Author

• Abdulrahman Ahmed Fathy Hgag

  Faculty of Biotechnology, Badr University, Alexandria, Egypt

  Author

• Menna Ezzat Elezaby

  Biotechnology Department, Faculty of Science, Mansoura University, Mansourah, Egypt

  Author

• Felopater Magdy Louka

  Biotechnology Department, Faculty of Science, October University for modern Science and Arts, October, Egypt

  Author

• Imene Maallem

  Chemistry Department, Faculty of Science, University of Montpellier, Montpellier, France

  Author

• Amany Sherif Mabrouk

  Biotechnology Department, Faculty of Agriculture, Cairo University, Cairo, Egypt

  Author

• Abdalla Adel Abdelfattah Mahmoud

  YS-G1004 Lab Department Of Cheminformatics EBO Bio Solution London United Kingdom

  Author

• Hussein Fayed

  Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

  Author

• Israa M Shamkh

  Chief Computational Chemistry Department EBO Bio Solution Company, London, EC1V2NX, United Kingdom

  Author

Abstract: Post-translational modifications (PTMs) regulate protein function, stability, and interaction networks, and are involved in the pathophysiology of diabetes mellitus through modulation of insulin signaling, β-cell function, and glucose metabolism. Aberrant PTMs contribute to insulin resistance, β-cell apoptosis, and metabolic dysregulation. This study applies a computational framework integrating molecular docking, molecular dynamics (MD) simulations, and virtual screening to investigate the structural and functional impact of PTMs on key diabetes-related proteins. Structural models incorporating phosphorylation, acetylation, ubiquitination, SUMOylation, and methylation were generated to assess conformational changes and ligand binding alterations. Proteins such as AKT2, IRS1, FoxO1, and PDX1 were prioritized based on their functional relevance and PTM profiles. Virtual screening of chemical libraries against PTM-modified protein structures, followed by MD simulations and free energy calculations, was conducted to identify small molecules capable of modulating PTM-influenced sites. Binding affinities, conformational stability, and drug-likeness parameters were analyzed to prioritize compounds for further investigation. The results provide a computational basis for targeting PTM-modified proteins in diabetes, supporting future experimental validation and development of PTM-focused therapeutic strategies.

1. Ahmed S Elfaki, Biotechnology Department, Faculty of Science, Cairo University, Cairo, Egypt

   Biotechnology Department, Faculty of Science, Cairo University, Cairo, Egypt

2. Lobna Badr, YS-G1004 Lab Department Of Cheminformatics EBO Bio Solution London United Kingdom

   YS-G1004 Lab Department Of Cheminformatics EBO Bio Solution London United Kingdom

3. Abdelrahman Mohamed Youseff Mohamed, Faculty of Science, Alexandria University, Alexandria, Egypt

   Faculty of Science, Alexandria University, Alexandria, Egypt

4. Abdulrahman Ahmed Fathy Hgag, Faculty of Biotechnology, Badr University, Alexandria, Egypt

   Faculty of Biotechnology, Badr University, Alexandria, Egypt

5. Menna Ezzat Elezaby, Biotechnology Department, Faculty of Science, Mansoura University, Mansourah, Egypt

   Biotechnology Department, Faculty of Science, Mansoura University, Mansourah, Egypt

6. Felopater Magdy Louka, Biotechnology Department, Faculty of Science, October University for modern Science and Arts, October, Egypt

   Biotechnology Department, Faculty of Science, October University for modern Science and Arts, October, Egypt

7. Imene Maallem, Chemistry Department, Faculty of Science, University of Montpellier, Montpellier, France

   Chemistry Department, Faculty of Science, University of Montpellier, Montpellier, France

8. Amany Sherif Mabrouk, Biotechnology Department, Faculty of Agriculture, Cairo University, Cairo, Egypt

   Biotechnology Department, Faculty of Agriculture, Cairo University, Cairo, Egypt

9. Abdalla Adel Abdelfattah Mahmoud, YS-G1004 Lab Department Of Cheminformatics EBO Bio Solution London United Kingdom

   YS-G1004 Lab Department Of Cheminformatics EBO Bio Solution London United Kingdom

10. Hussein Fayed, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

    Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

11. Israa M Shamkh, Chief Computational Chemistry Department EBO Bio Solution Company, London, EC1V2NX, United Kingdom

    Chief Computational Chemistry Department EBO Bio Solution Company, London, EC1V2NX, United Kingdom

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Copyright (c) 2025 Ahmed S Elfaki, Hussein Fayed, Abdalla Adel Abdelfattah Mahmoud, Amany Sherif Mabrouk, Imene Maallem, Felopater Magdy Louka, Menna Ezzat Elezaby, Abdulrahman Ahmed Fathy Hgag, Abdelrahman Mohamed Youseff Mohamed, Lobna Badr, Israa M Shamkh (Author)

This work is licensed under a Creative Commons Attribution 4.0 International License.

This work is licensed under a Creative Commons Attribution 4.0 International License.