In contrast, the relative performance of constant pH simulations based on the linear interpolation of potential energy functions, decreases with the number of titratable sites in the system. This comparison thus demonstrates that by replacing linear interpolation of potentials by linear interpolation of partial charges, we have overcome the major bottleneck in the earlier constant pH implementation in the fork of GROMACS 3.3 release, and paved the way towards simulations of large biomolecular systems at constant pH. An example of such a large system is the proton-gated ion channel GLIC, a membrane protein with 185 titratable residues. Figure shows the performance of the new implementation for this large system when running the simulation on CPU and on a combination of CPU and GPU.