Based on standard, we added five additional active site residues to the minimal QM region (ASP140, LYS143, ASP168, ASN169 and GLU198 ) to assess the effect of a larger QM region including ligands and catalytically important residues on the saaPCVA results (referred to as active). Similarly, we tested the no lig approach, in which the aforementioned active site residues form the QM region, but the ligands are completely removed from the system to investigate whether ligands are crucial for PCVA or whether there is no need to include them, which can save efforts for parametrizing the ligands.