Computational Insights into the Allosteric Behavior of Mini-Insulin in Receptor Binding Driven by C-Peptide Mobility
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Background/aim
The production of recombinant insulin remains challenging, particularly in enhancing refolding efficiency and bioactivity. Mini-proinsulin analogs, which involve reducing the length of the C-peptide, offer potential improvements in insulin production. This study aims to evaluate mini-proinsulin analogs’ design and receptor binding dynamics to optimize recombinant insulin production in E. coli .
Materials and methods
Mini-proinsulin analogs were engineered by replacing the 33-residue C-peptide with a pentapeptide sequence to improve refolding. The three-dimensional structure of mini-proinsulin was predicted using AlphaFold and performed docking analysis of mini-analogs to the insulin receptor using AutoDock Tools, with comparisons made to previously available NMR-determined analog and the native insulin-insulin receptor complex. Normal Mode Analyses (GNM and ANM) were performed in detail to assess binding dynamics.
Results
In silico analyses revealed that mini-proinsulin analogs closely replicate the structural features of native insulin and display receptor binding dynamics similar to native insulin, though they follow distinct receptor interaction paths.
Conclusion
All analysis suggests that C-peptide mobility may contribute to the allosteric behavior observed in mini-proinsulin analogs during receptor interaction.
