Theoretical analysis of an energy barrier model for the electrical properties of a biological membrane yields new results. Discontinuities at the membrane-solution interfaces are crucial and receive careful attention, as does the polarization charge density due to electroneutral but polarized ion distributions. The topics explored include the equilibrium and time-dependent Nernst potential, the resting potential, the capacitance-resistance equation for membrane voltage, and large electrical effects on osmosis (bulk volume flow). The generalization of Nernst–Hartley salt diffusion to the diffusion of mixed salts as a necessary tool is accomplished. The electric field inside the membrane is especially strong at the membrane-solution interfaces. The analysis of the resting potential differs from the Goldman–Hodgkin–Katz formulation but predicts realistic numerical values for animal cells and also captures the effect of switching sodium and potassium ion permeabilities. An analysis of the physical basis of bulk water flow in the presence of impermeant and permeant ions, that is, Donnan osmosis, reveals large ion charge effects that have not previously been considered. The equation derived here for Donnan osmotic flow helps to explain why the action of the sodium pump is essential for the prevention of excessive osmotic stress on cellular membranes.

While the structure of proteins can now be predicted from sequence with high certainty, the prediction of protein functional dynamics remains to be achieved. Progress towards this goal will require a much larger experimental database of the relationships among sequence, dynamics, and function than currently available. Dynamic transitions that are key to protein function and turnover remain difficult to access and characterize because they have significantly higher free energy than the folded states of proteins and hence are not populated. To access these higher free energy states, proteins must be perturbed. High temperatures often lead to aggregation, while chemical denaturants, because they interact with the entire protein backbone, tend to smooth protein conformational landscapes. In contrast, high hydrostatic pressure represents a continuous and reversible variable that can perturb protein structure locally around internal cavities, leading to partial structural disruption, populating these higher energy states sufficiently for their characterization.