Structural Insights into the IL12:IL12 Receptor Complex Assembly by
Molecular Modeling, Docking, and Molecular Dynamics Simulation

Sakshi       Singh; Geeta       Rai

doi:10.2174/1386207323666201207113745

Abstract

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 known.

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 and IL12R.

RResults: 3D structure prediction and validation confirm 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.

Keywords: IL12:IL12R complex, homology modeling, molecular docking, molecular dynamics simulation.

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DOI https://dx.doi.org/10.2174/1386207323666201207113745	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

Combinatorial Chemistry & High Throughput Screening

Structural Insights into the IL12:IL12 Receptor Complex Assembly by Molecular Modeling, Docking, and Molecular Dynamics Simulation

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