TITLE:
Systematic Analysis of Post-Translational Modifications for Increased Longevity of Biotherapeutic Proteins
AUTHORS:
Justin Kim, Karanveer Sadiora
KEYWORDS:
Post-Translational Modification, Protein-Based Therapeutics, Therapeutic Half-Life, Protein Aggregation, Protein Reception
JOURNAL NAME:
Computational Molecular Bioscience,
Vol.14 No.3,
September
10,
2024
ABSTRACT: Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p