The protein is treated with PDBFixer 38 to add any missing atoms, residues and hydrogen atoms. Water molecules (and other non-protein residues) are stripped by default, but can be optionally retained, for example if they are thought to form an important part of the hydrogen bonding network within the binding pocket. A simple distance filter removes any ligand conformers that form a steric clash with the protein (any atom-atom distance less than 1 Å). Next, the remaining conformers are refined in the context of a rigid receptor via energy minimisation using OpenMM. The simulation uses the AMBER FF14SB 39 force field for the receptor and either GAFF2 (General AMBER force field) or the Open Force Field 1.0.0 ('Parsley') general force fields for the ligand, with the choice left to the user. Optionally the intramolecular interactions of the ligand can be modelled using the ANI2x ML potential 28 in a hybrid ML/MM simulation.