The λ schedule used in the OpenMM calculations was a two-step procedure which completely annihilated all electrostatic interactions of outgoing alchemical moieties before scaling down the LJ interaction, and completely created all LJ interactions of incoming moieties before turning on any electrostatic interactions. Annihilation was used in the OpenMM method as this is the methodology supported by OpenMMTools when calculating the electrostatics with the particle-mesh Ewald method, which was used for all simulations in this work. In this context, annihilation means that when a chemical moiety is "turned off" both inter and intra molecular interactions are extinguished.