In the problem of protein-ligand docking, most of the time people are happy if they can just predict the final conformation the ligand adopts into the protein's binding pocket. Most of the time one can just use a physical based scoring function and an energy minimization method to try to find the minima. But in some other cases, scoring functions are very inaccurate to represent some more complex interactions; metal interactions, cation-pi, etc., and even covalent bonding. So it seems that only ab-initio methods can shed light here.
Can quantum mechanical methods be used in docking for this purpose or not and which are the best methods, even if you require access to HPC resources?
I am mostly interested in covalent bond formation. It would be great also if you could provide some references, I did not find many in the literature.