Molecular Docking of VCP Inhibitors

All molecular docking experiments were carried out with AutoDock Vina.^{29 (link)} The structure of VCP was acquired from the protein data bank (PDB code 5FTK), and modified by removing the bound ADP and solvent molecules, and converted to a hexameric form for CB-5083 and NMS-873.^{2 (link)} Auto-DockTools 4.2 was utilized to add polar hydrogens and Gasteiger charges and to position a 30×30×30 ų search box that included both E470 and the active site.^{33 (link)} Structure coordinates of compounds of interest were built using Phenix and then converted to a.pdbqt format with Auto-DockTools 4.2, allowing full ligand flexibility.^{34 (link)} Default Autodock Vina settings were utilized for the analysis of binding modes, except that exhaustiveness was raised to 100. Measurements and figures were made in PyMol.³⁵