Based on accuracy DF-MP2-F12/cc-pVTZ-F12 performs the best compared to the reference method, but as mentioned, computational wall time is also a significant factor. DF-MP2-F12/cc-pVTZ-F12 took about 200 hours to optimize one of the larger systems ((MSA) 1 (TMA) 1 ) in the dimer cluster test set while DF-MP2/aug-cc-pVQZ only took about 4 hours. Even though DF-MP2-F12/cc-pVTZ-F12 would be the best choice, it is simply not feasible when going to larger cluster sizes containing up to four monomers. Hence, based on both the calculated D e -values and the RMSD, we will employ the DF-MP2/aug-cc-pVQZ level of theory as the reference method for optimizing the geometries of the large 1283 cluster test set.