Ions in water are important in biology, from molecules to organs.
Classically, ions in water are treated as ideal noninteracting particles in a
perfect gas. Excess free energy of ion was zero. Mathematics was not available
to deal consistently with flows, or interactions with ions or boundaries.
Non-classical approaches are needed because ions in biological conditions flow
and interact. The concentration gradient of one ion can drive the flow of
another, even in a bulk solution. A variational multiscale approach is needed
to deal with interactions and flow. The recently developed energetic
variational approach to dissipative systems allows mathematically consistent
treatment of bio-ions Na, K, Ca and Cl as they interact and flow. Interactions
produce large excess free energy that dominate the properties of the high
concentration of ions in and near protein active sites, channels, and nucleic
acids: the number density of ions is often more than 10 M. Ions in such crowded
quarters interact strongly with each other as well as with the surrounding
protein. Non-ideal behavior has classically been ascribed to allosteric
interactions mediated by protein conformation changes. Ion-ion interactions
present in crowded solutions--independent of conformation changes of
proteins--are likely to change interpretations of allosteric phenomena.
Computation of all atoms is a popular alternative to the multiscale approach.
Such computations involve formidable challenges. Biological systems exist on
very different scales from atomic motion. Biological systems exist in ionic
mixtures (extracellular/intracellular solutions), and usually involve flow and
trace concentrations of messenger ions (e.g., 10-7 M Ca2+). Energetic
variational methods can deal with these characteristic properties of biological
systems while we await the maturation and calibration of all atom simulations
of ionic mixtures and divalents