Predicted IL-18/IL-18R Binding Improvement Through Protein Interface Modification with Computer-Aided Design
Issued Date
2025-10-01
Resource Type
eISSN
2218273X
Scopus ID
2-s2.0-105020053924
Journal Title
Biomolecules
Volume
15
Issue
10
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomolecules Vol.15 No.10 (2025)
Suggested Citation
Prompat N., Peeyatu C., Saetang J., Roongsawang N., Sangkhathat S., Tipmanee V. Predicted IL-18/IL-18R Binding Improvement Through Protein Interface Modification with Computer-Aided Design. Biomolecules Vol.15 No.10 (2025). doi:10.3390/biom15101360 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112917
Title
Predicted IL-18/IL-18R Binding Improvement Through Protein Interface Modification with Computer-Aided Design
Corresponding Author(s)
Other Contributor(s)
Abstract
Cytokine-mediated immunotherapy has rapidly emerged as an effective alternative approach for cancer treatment by modulating the anti-tumor response. Interleukin-18 (IL-18) is considered as a promising cancer therapeutic agent due to the ability of cytokines to inhibit cancer by enhancing natural killer (NK) cell and cytotoxic T cell responses. Since the activity of IL-18 is required for the specific binding to IL-18 receptors, the modification of binding residue at the protein interface is an attractive strategy for IL-18 activity enhancement. The aim of this study was to design and predict mutations increasing the activity of IL-18 through computational structure-based energy calculation and molecular dynamic simulations. Four candidate mutations, E6M, E6M+N111S+R131G, E6M+K129M+R131G, and E6M+N111S+K129M+R131G, could affect/facilitate the receptor binding and stability compared to the wild-type via electrostatic interaction. MD simulations demonstrated that the predicted mutation on IL-18 had no influence on the overall conformation stability, but increased flexibility in the β8–β9 hairpin loop. Furthermore, the dynamic behavior suggested that these candidates could be an alternative for the improvement of IL-18 biological activity, though the full simulation of the IL-18 complex remains necessary. In summary, this study offered a computer-aided design strategy which was of beneficial use in the design and development of IL-18 to increase its cytokine potency and efficiency.