Molecular Docking of PW201 to FGF14:Nav1.6 Complex

The molecular docking study was performed using Schrödinger Small-Molecule Drug Discovery Suite (Schrödinger, LLC, New York, NY, USA). The FGF14:Na_v1.6 homology model was built using the FGF13:Na_v1.5:CaM ternary complex crystal structure (PDB code: 4DCK) as a template [14 (link)]. The FGF14:Na_v1.6 CTD homology model was prepared with Schrödinger Protein Preparation Wizard using default settings. The SiteMap (Schrödinger, LLC) calculation was performed, and a potential binding site was identified on the PPI interface of FGF14 and the CTD of the Na_v1.6 channel. The docking was performed on the CTD of Na_v1.6 after removing the FGF14 chain structure. The grid center was chosen on the Na_v1.6 CTD at the previously identified binding site with a grid box sized in 24 Å covering the PPI surface on the Na_v1.6 CTD. The 3D structure of PW201 was created using Schrödinger Maestro and a low-energy conformation was generated using LigPrep. Docking was then employed with Glide using the SP precision. Docked poses were incorporated into Schrödinger Maestro for a ligand–receptor interactions visualization. The top docked pose of PW201 was superimposed with the FGF14:Na_v1.6 CTD complex homology model for an overlay analysis.