Water wires in atomistic models of the Hv1 proton channel

► Two homology models of the Hv1 proton channel are presented. ► The models are based on two alignments with the voltage-sensing domain of a potassium channel of known structure. ► Both models support water wires, but the wire is more stable in one of the models. ► No water flux is observed in the model with the most robust water wire. ► The model with the most robust wire is supported by experimental studies and modeling of a mutant.