We ran 3 independent simulations of 60 ns for each mode. The different sampled basins are also compared to a 1 µs cMD AMOEBA reference. are depicted on Figure and show that GaMD-dual captures well the α r (50°,25°), α L (-75°,-25°) and P II (-75°,150°) basins. These results are consistent with the 1 µs cMD trajectory (see Figure in SI) depicting these three basins. While the GaMD-dih mode captures the α r basin after 150 ns, the GaMD-dualwat captures it in 100 ns (SI Figure ). We also observe a sampling acceleration between GaMD-dual and GaMD-dualwat compared to the reference 1 microsecond cMD. To characterize the GaMD boost harmonicity, its distribution anharmonicity γ is calculated as in. γ serves as an indicator of the sampling convergence and reweighting procedure accuracy. Depicted on Figure in SI GaMD-dih as well as GaMD-dual depicts high anharmonicity with respectively 0.252 and 0.016 compared to GaMD-dualwat with 0.0005. Additionally, we see a steep anharmonicity convergence to less than 10 -3 for GaMD-dualwat while being relatively stable at 2 × 10 -1 for GaMD-dih (SI Figure ). In comparison the anharmonicity is about 0.001 with GaMD-dih and AM-BER99SB. PFFs thus increase the statistical noise and stress the importance of using low anharmonicity GaMD modes. In that sense, GaMD-dualwat appears more suitable than GaMD-dual for PFFs simulations with an anharmonicity equal to 0.0005. As stated before, another advantage of GaMD-dualwat is that it can be coupled to multiple-time-step such as BAOAB-RESPA1 17 in contrast to the GaMD-dual mode that remains limited to single timestep integrators. Comparative results of GaMD-dualwat with both integrators can be found in Figure of the SI. Its coupling with multiple-time-step clearly compensates the slightly lower sampling performance compared with GaMD-dual. The sampling enhancement brought by the GaMD-dualwat can be partly related to how it affects the diffusion of water: we report in Table of the SI the self diffusion coefficients of bulk water computed within a same setup (same size of box and same integrator) and observe that it is increased with the GaMD-dualwat mode compared to the simple GaMD-dih one, favoring global conformationnal changes due to water reorganization. While the added sampling efficiency is already significant for the alanine dipeptide, we expect it to be larger on more complex and larger biological systems such as CD2CD58 where water reorganization plays a bigger role.