To understand the discrepancies between periodic DFT and periodic QM/MM simulations, we performed a QM/MM simulation on a large spherical droplet, with a central OH(H 2 O) 64 region described at the PBE0 + D3/ 6-31+G* level. The O * • • • O RDF from this trajectory (Fig. ) resembles the periodic ones in Fig. much more closely than do the periodic QM/MM results in Fig. where the QM region is OH(H 2 O) 31 . This indicates that finite QM size effects in QM/MM simulations can have just as significant of an impact as SIE artifacts or finite unit cell size.