The butanol in acetone system consists of one butanol (QM) and 13,948 acetone molecules (MM) giving a total of 139,495 atoms, which thus represents a system with a small QM subsystem and a large MM subsystem. The 16 orbitals of butanol were expanded on a real-space FFT mesh of 240 3 points corresponding to a plane wave cutoff of 85 Ry. The number of atoms in the solvated MQAE system is 16,396 of which either 34 (MQAE) or 151 (MQAE + 39×H 2 O) are in the QM subsystem, representing systems with a small and a large QM subsystem, respectively, together with a small MM subsystem. At a cutoff of 80 Ry, the 47 orbitals of the small QM subsystem are expanded on a mesh of 216 3 points, whereas the 203 orbitals of the large QM subsystem are expanded on a 288 3 mesh. The protein systems considered here also vary in size. The GB1 system contains 25,976 atoms in total, 40 of which were treated at the QM level (small QM and small MM). Using a cutoff of 85 Ry, the 57 orbitals were mapped on a mesh containing 240 3 points. The ClC-ec1 system consists of 150,925 atoms, where either 19 or 295 atoms were selected to represent a small and large QM subsystem, respectively, combined with a large MM subsystem. The real-space mesh for the small and large QM subsystems consist of 240 3 and 360 x 300 x 300, respectively, corresponding to a 90 Ry cutoff. The amount of orbitals totalled 49 in the small QM subsystem and 383 in the large QM subsystem. Apart from the MQAE and ClC-ec1 setups with large QM regions, which were only treated at the BLYP level, benchmarks for all other systems were performed using the GGA XC functional BLYP as well as the hybrid-GGA XC functional B3LYP. All simulations were performed using Troullier-Martins norm-conserving pseudopotentials using the new XC driver by Bircher and Rothlisberger. Note that the setups detailed above do not necessarily correspond to a realistic setup suitable for a production simulation but are prepared in order to demonstrate the performance of systems with different QM and MM subsystem sizes. The timings are given as averages over 5 steps in BO-MD and 10 steps in CP-MD. However, in the case of BO-MD using B3LYP, only 3 time steps were used due to the large amount of time needed when running on a single node.