The crystal structure of the catalytically trapped HIV-1 RT DNA/RNA complex by Huang et al. (PDB: 1RTD) with 3.2 Å resolution was used as a starting model. The active site of RNase H was modeled with SWISS-MODEL based on the higher resolution structure of D192N Bh RNase H catalytic domain by Nowotny et al. with 2.2 Å resolution (PDB: 1ZBL) to achieve appropriate coordination of the metal ions and proper orientation of the substrate. The obtained model was compared with the recently published catalysisready structure of RNase H in HIV-1 RT (RMSD 0.822 Å, PDB 6BSH). The DNA/RNA hybrid of the crystal was replaced with the polypurine tract (PPT) sequence. The RNase H reaction has a pH profile with maximum activity at pH 7.5. All carboxylate active site residues were therefore considered deprotonated at first and H1126 was modelled as -protonated, while standard protonation states were used for all the remaining titrable residues. The model was subject to classical MD equilibration of 20 ns and QM/MM minimizations to relax the active site before the restrained energy minimizations along the RC were performed and the relaxed geometries were then finally used for QM/MM simulations. The details about the simulations are shown below.