Transportation of material across a cell membrane is a vital process for maintaininghomeostasis. Na+/H+ antiporters, for instance, help maintain cell volume and regulate intracellular sodium and proton concentrations. They are prime drug targets, since dysfunction of these crucial proteins in humans is linked to heart and neurodegenerative diseases. Due to their placement in a cell membrane, their study is particularly difficult compared to globular proteins, which is likely the reason the transport mechanisms for these proteins are not entirely known. This work focuses on the electrogenic bacterial homologs Thermus thermophilus NapA (TtNapA) and Echerichia coli NhaA (EcNhaA), each transporting one sodium from the interior of the cell for two protons on outside of the cell. Even though X-ray crystal structures for both of these systems have been resolved, their study through molecular dynamics (MD) simulations is limited. The dynamic protonation and deprotonation of the binding site residues is a fundamental process in the transport cycle, which currently cannot be explored intuitively with standard MD methodologies. Apart from this limitation, simulation performance is only a fraction of what is needed to understand the full transport process, particularly when it comes to global conformational changes. This work seeks to overcome these limitations through the development and application of a multiscale thermodynamic and kinetic framework for constructing models capable of predicting experimental observables, such as the dependence of transporter turnover on membrane voltage. These models allow interpretation of the effects of individual processes on the function as a whole. This procedure is demonstrated for TtNapA and the connection between structure and function is shown by computing cycle turnover across a range of non-equilibrium conditions.