Constraints used in modeling transport. These constraints are based on experimental observations for EmrE. (A) Both drug- and proton-on rates are diffusion-limited and constant. (B) Binding affinities are the same for open-in and open-out conformations of the transporter. Additionally, these four values are constrained by the thermodynamic cycle (⁠$pKa1+pKD2=pKD1+pKaD$⁠). (C) All alternating access rates are equal going in either direction. Colors are as in Figs. 1, 2, and 3.