Energy landscapes and dynamics of ion translocation through membrane transporters: a meeting ground for physics, chemistry, and biology

The dynamics of ion translocation through membrane transporters is visualized from a comprehensive point of view by a Gibbs energy landscape approach. The Delta G calculations have been performed with the Kirkwood-Tanford-Warshel (KTW) electrostatic theory that properly takes into account the self-energies of the ions. The Gibbs energy landscapes for translocation of a single charge and an ion pair are calculated, compared, and contrasted as a function of the order parameter, and the characteristics of the frustrated system with bistability for the ion pair are described and quantified in considerable detail. These calculations have been compared with experimental data on the Delta G of ion pairs in proteins. It is shown that, under suitable conditions, the adverse Gibbs energy barrier can be almost completely compensated by the sum of the electrostatic energy of the charge-charge interactions and the solvation energy of the ion pair. The maxima in Delta G(KTW) with interionic distance in the bound H+ - A(-) charge pair on the enzyme is interpreted in thermodynamic and molecular mechanistic terms, and biological implications for molecular mechanisms of ATP synthesis are discussed. The timescale at which the order parameter moves between two stable states has been estimated by solving the dynamical equations of motion, and a wealth of novel insights into energy transduction during ATP synthesis by the membrane-bound FOF1-ATP synthase transporter is offered. In summary, a unifying analytical framework that integrates physics, chemistry, and biology has been developed for ion translocation by membrane transporters for the first time by means of a Gibbs energy landscape approach.

Automated summary

The dynamics of ion translocation through membrane transporters is visualized using a Gibbs energy landscape approach, calculating Delta G with the KTW electrostatic theory and comparing single charge translocation with ion pair translocation. The system characteristics of the ion pair with bistability are described in detail, and the compensatory mechanisms for adverse Gibbs energy barriers are discussed. The timescale of transition between stable states and insights into energy transduction during ATP synthesis by membrane-bound FOF1-ATP synthase transporter are also explored, offering a unifying analytical framework integrating physics, chemistry, and biology for ion translocation by membrane transporters.