Structural Modeling and Molecular Docking of IFNAR2

Prior to molecular docking calculations, we constructed the IFNAR2 model structure using the X-ray crystallographic structure of IFNAR2 (PDB ID: 3S9D) [25 (link)]. IFN-α2 and water molecules were removed, and the protein structure was prepared using Schrödinger Protein Preparation Wizard of maestro module (Schrödinger, New York, NY, USA) [26 ]. Docking center was set to the loop that included Tyr39 and Tyr43. We used a compound library for docking simulations provided by Namiki Shoji (Tokyo, Japan). The compound library was filtered using Lipinski’s rule of five, resulting in exclusion of compounds with reactive groups and selection of approximately 300,000 compounds at random. Alternative protonation states of each compound as well as chiral forms were generated for the 7 ± 2 pH range using the LigPrep module and ionization penalties were calculated using the Epik panel (Schrödinger, NY, USA) at pH 7 [27 ]. The docking simulations were performed using GOLD with GoldScore (The Cambridge Crystallographic Data Center, Cambridge, UK) [28 (link)], Glide (SP mode) with GlideScore (Schrödinger, NY, USA) [29 ], and Molecular Operating Environment (MOE) Docking score (S score) (Chemical Computing Group, Montreal, Canada) [30 ].