Background: Interleukin-12 receptor (IL12R) is a type I cytokine receptor that can promote hematopoiesis and
regulate innate and adaptive immunity. It binds with the IL12 ligand, which activates the IL-12 signaling pathway that
triggers hematopoietic progenitor cell proliferation and differentiation process. The structure of IL12:IL12R complex is not
Objective: The present work describes a de novo computational method for rational protein designing to elucidate the
structure of IL12:IL12R complex.
Methods: Homology modeling, docking, and MD simulation methods were used to design mimics of the interaction of IL12
Results: 3D structure prediction and validation confirms the accurate structure of IL12R protein that contains immunoglobin
domain, fibronectin type three domain, cytokine-binding domain, and WSXWS motif. Molecular docking and MD
simulation revealed that IL12R bound tightly with IL12 ligand at their interface. The estimated binding energy of the
docked complex was -26.7 kcal/mol, and the interface area was 281.4 Å2. Hotspot prediction suggested that ARG34, SER58,
GLU61, CYS62, LEU63, SER73, ASP142, GLN146, LYS168, THR169 ARG181, ARG183, ARG189, and TYR193 residues in IL12
ligand interacted with SER175, ALA176, CYS177, PRO178, ALA179, ALA180, GLU181, GLU182, ALA192, VAL193, HIS194,
ARG208, TYR246, GLN289, ASP290, ARG291, TYR292, TYR293 and SER294 residues in IL12 receptor.
Conclusion: The results of the study provides a simulated molecular structure of IL12:IL12R complex that could offer a
promising target complex to substantiate IL12 based drug-designing approaches.