and k the harmonic force constant. The two adjustable GaMD parameters k and E are automatically determined following the original procedure described in ref . The boost intensity can be managed thorough a user-specified uper limit labeled as σ 0 (e.g 10k B T ) predefined before the simulation. To ensure accurate reweighting with the cumulant expansion the ∆U GaM D standard deviation, σ ∆V , should satisfy σ ∆V < σ 0 . GaMD provides different modes: the boost is either applied on the total potential GaMD-pot, on the dihedral potential GaMD-dih, or on both at the same time GaMD-dual . Recently, another mode was introduced:LiGaMD which adds the boost to a ligand non bonded interactions, accelerating the sampling of ligand-protein interactions. It is known that interactions involving water are essential for such systems and that protein stability processes are controlled by water-protein interactions. To accelerate these interactions, one would like to use the GaMD-dual mode on the non bonded interactions of water molecules. However, such boost requires the evaluation of the complete non bonded energies and, in the context of multitimestep integrators such as BAOAB-RESPA1 where they are split between short and long range, these are only available at outer (large) timestep. This type of integrators enables the use of larger time steps and thus a direct acceleration of molecular dynamics. For example, the BAOAB-RESPA1 is based on a RESPA (Reference System Propagator Algorithm ) three-level splitting of forces (bonded, short-range non-bonded and long-range non-bonded) within the Leimkuhler's BAOAB discretization of Langevin dynamics. It allows up to a 7 folds acceleration for polarizable point dipole molecular dynamics. But the fluctuations of the associated bias are such that it has to be evaluated at shorter timesteps, so that the whole procedure is not compatible with multi-timestep integrators such as BAOAB-RESPA1. For similar reasons, the GaMD-dual mode with a bias applied to the complete potential en-ergy is not compatible with even simple RESPA integrators in which the potential energy is split between bonded and non bonded terms. Therefore, GaMD-dual mode becomes rapidly limited by the simulation time. To overcome this issue, we developed a new mode, GaMDdualwater (denoted GaMD-dualwat), which adds a boost to the protein dihedral potential energy term and the water stretching and bending terms, this time fully compatible with RESPA and RESPA1 like integrators, allowing water molecule to be more flexible and thus favoring their conformational changes.