Ligand Docking with Autodock (Version 4.2)

Proteins and ligand pdbqt files were prepared using standard AutoDock tools (prepare_flexreceptor4.py and prepare_ligand4.py). These files include Cartesian coordinates and Gasteiger atomic charges⁹⁵ for each atom. AutoDock employs a united atom method, and thus, no nonpolar hydrogens are present. The center of mass of the crystallographic ligand was used to determine the center of the grid. AutoDock uses one grid box to perform the docking calculations, and the dimensions of this box were set to 37.5 × 37.5 × 37.5 ų and the spacing was set to 0.375 Å for all systems. We performed flexible ligand docking into a rigid protein environment using GA, with default settings. For covalent docking,⁹⁶ each ligand was prepared with the active Cys residue already present in the input file using AutoDock tools (prepare_receptor4.py and prepare_flexreceptor4.py). For covalent docking, the ligand flexible torsional angles were presampled using MC simulations with CHARMM prior to docking.