Identification of ZINC08101049 as a potential IL1β inhibitor through molecular docking and MD simulations for cancer therapeutics

Abstract

Cancer is a significant global health concern that has a major impact on morbidity and mortality worldwide. Research has demonstrated the involvement of Interleukin-1 beta (IL1β) in various aspects of cancer development and progression, including angiogenesis, tumor growth and metastasis. Consequently, targeting IL1β activity represents a promising approach for cancer therapeutics. In this study, we utilized molecular docking and MD simulations to discover potent IL1β inhibitors for the treatment of cancer. Five thousand compounds from ZINC15 database were screened against IL1β target, and the top ten small molecules were selected based on their binding energy. The small molecule named ‘ZINC08101049’ was prioritized based on binding energy (−9.1 kcal/Mol) and residual interaction specifically forming seven hydrogen bonds with amino acid residues namely GLN81, GLY136, LEU134, LYS138, SER84, THR137 and TYR24 of IL1β. Next, IL1β alone and in complex with ZINC08101049 was subjected to MD simulations to determine their behavior at atomic level. The results of molecular docking and MD simulation revealed ZINC08101049 as a potential inhibitor of IL1β, reflecting that ZINC08101049 can emerge as a promising small molecule paving for cancer therapeutics.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cancer
• IL1β
• molecular docking
• MD simulation
• therapeutics
• ZINC08101049

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through the Large Research Groups Project under grant number (RGP.2/119/44).

Authors’ contributions

Conceptualization, M.Y.A. and S.W.; methodology, M.S.; software, S.W.; validation, M.Y.A., S.W and M.S.; formal analysis, S.W.; investigation, S.W.; resources, M.Y.A.; data curation, S.W. and M.A.A.A; writing – original draft preparation, S.W.; writing – review and editing, S.W. and M.A.A.A; visualization, M.Y.A; supervision, M.S.; project administration, M.Y.A; funding acquisition, S.W; All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The original contributions presented in the study are included in the article; further inquiries can be directed to the corresponding authors.

Additional information

Funding

This work was supported by the Deanship of Scientific Research at King Khalid University through the Large Research Groups Project under grant number (RGP.2/119/44).