I am running a B3LYP-D3/6-31+G geometry optimization of a protein-ligand interaction. Well, not quite, I have simplified the protein to four amino acids surrounding the active site, but I keep the entire ligand (170 atoms total).
I am wondering if I should optmize the geometry in solution, i.e. will including solvation effects make my results (energies) be more realistic? My mind is split.
On the one hand, I am modelling a biological system which usually takes place in aqueous solution. On the other hand, my system is so simplified, that it no longer has much root in reality. By "placing my molecules in water", the water molecules will interact with parts of my system that otherwise would not interact as strongly (there would be much less water inside the protein than outside it, I mean). So, I feel there is no guarantee that my results will improve, and I am not able to find any data indicating one or the other. If I included the entire protein, then the case would be different, perhaps, since at least then that protein would be "solvated correctly".
So, given the simplified system, will solvation improve the resulting geometry, and thus the interaction energy between the protein residues and the ligand, or not?