Molecular Dynamics Simulations on the Interleukin-1β:Interleukin Receptor I:Interleukin-1 Receptor Accessory Protein Ternary Complex



Joshi, Reva

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Osteoarthritis affects millions of people worldwide each year. The inflammatory signaling pathway associated with osteoarthritis contains a possible novel drug target, the IL-1β ternary complex. IL-1β interacts with two associated proteins, IL-1RI and IL-1RAcP, to exert downstream inflammatory effects. Experimental studies of this complex have identified residue Arg-286 of IL-1RAcP as a “hot spot” of interaction. This paper aimed to computationally study the IL-1β complex with molecular mechanical and quantum mechanical methods. The study found Arg-286 of IL-1RAcP to be the hot spot, participating in a hydrogen bond with Asp-54 of IL- 1β. In agreement with previous experimental studies, Arg-286 was identified as a possible target for drug discovery aimed at inhibiting IL-1β complex and its ultimate downstream inflammatory effects.



Molecular dynamics, Fragment Molecular Orbital Method, Amber MD, Interleukin-1ß