PT  - JOURNAL ARTICLE
AU  - Ayan, Esra
TI  - Computational Insights into the Allosteric Behavior of Mini Proinsulin Driven by C Peptide Mobility
AID  - 10.1101/2024.10.05.616825
DP  - 2025 Jan 01
TA  - bioRxiv
PG  - 2024.10.05.616825
4099  - http://biorxiv.org/content/early/2025/01/11/2024.10.05.616825.short
4100  - http://biorxiv.org/content/early/2025/01/11/2024.10.05.616825.full
AB  - 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-proinsulin 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.Competing Interest StatementThe authors have declared no competing interest.