Do you know how to compute binding energy using Gaussian? I have optimized binding pocket with ligand using ONIOM methodology implemented in Gaussian16. For the high layer B3LYP/6-31+G(d,p) was used, while low layer with PM6 method. Then, I recomputed the system without ligand and hence used only PM6 for the aminoacids. I though the way would be to subtract the energies of the system with and without ligand but it actually makes no sense for ONIOM total energy equals -1029.031167au and PM6 energy is -1.261231au.
Thanks in advance !