In contrast to when potential energy functions are interpolated, the same electrostatic potential is used to evaluate the electrostatic forces on both the atoms and the λ-particles. Therefore, a single electrostatic calculation per time step suffices. If the electrostatic interactions are modeled with the smooth Particle Mesh Ewald method, 36,37 the short-range real-space interactions and long-range reciprocal-space interactions are computed separately. For the pair-wise short-range interactions in real space an additional calculation for each interacting pair and a subsequent accumulation of the potential at each atom is needed. Whereas this calculation comes at no extra computational cost if the standard pair interaction kernels are used, the accumulation leads to a measurable computational overhead, as we will show later.