A network thermodynamic approach to the Hill-King and Altman approach to kinetics: computer simulation.

The network simulation of kinetic systems is a rather painless way to produce dynamic analogs of these models without becoming involved in needless mathematical difficulty. The methods of King and Altman, Hill, Mason, and others fall into a universal paradigm applicable in both the kinetic and thermodynamic coordinate systems. (It is a small extra step to turn the state concentrations into chemical potentials and affinities using diode subcircuits during any simulation. This will be spelled out in detail in future work. Thus the simulation can be carried out using the exact kinetic rate laws, but the results are readily put into a form which allows the energetics to be analyzed as well). Another virtue of network modeling and simulation is the hierarchical nature of the networks and its correspondence to that of the living system. It is now possible to simulate complicated multicellular epithelial membranes with channels and/or carriers in certain selected cell membranes. The only limitation to progress in this area is the lack of experimental information to feed into the models. On the other hand, the network models are rapidly becoming an indispensable aid in experimental design for precisely this reason. Living systems have always been characterized by their morphology to a great extent. There is no reason why that morphology can be ignored as their function is analyzed. In the past, it often had to be simplified due to the weakness of the analytical tools available. Now, by utilizing the same methods that have caused an explosion of progress in electronics, it is possible to hope to understand the structure-function relationship of living systems with equal facility. The challenge remaining is to develop experimental techniques which will keep up with the demand for information generated by the models.