Effect of SQM geometry optimization on the PM6/COSMO interaction energy SQM optimization of the protein residues can induce drastic conformational changes, which in turn has an impact on the interaction free energy. In Figure we demonstrate the effect of such choice on the binding mode of active compound BDB50322767 of Acetylcholinesterase (ACHE). The inclusion of protein residue in the SQM part results in the flipping of the ligand's aromatic ring and different packing of the protein sidechains but also in a dramatic drop of the interaction energy.