DEVELOPMENT OF KINETIC-MODELS IN THE NONLINEAR WORLD OF MOLECULAR CELL BIOLOGY

Increasingly, successful research on metabolic systems relies on teams of specialists. Because of the enormous complexity of these systems, many experimental groups have sought collaborations with theoreticians for data analysis and modeling. Predictably, cultural differences in scientific approach, methodology, assumptions, and language have led t o some persistent difficulties in communication across the experiment- theory frontier. This report attempts to diagnose some of these diffic ulties from the perspective of 30 years' experience in both experiment al and theoretical biology, and to suggest guidelines for effective. c ollaboration between experimentalists and theorists. As these collabor ations move to the level of cellular and molecular biology, effective communication will become all the more important because the simple li near rate laws of radiotracer and stable-isotope kinetics will no long er suffice. This is because every form of regulation and control, hall marks of metabolic systems, results in nonlinear kinetics. To advance this transition to nonlinear cellular and molecular metabolic models a nd to facilitate communication between experimental and theoretical co llaborators, a general procedure for incorporating control mechanisms in metabolic rate laws is developed based on the familiar rapid-equili brium assumption of classical enzyme kinetics. Copyright (C) 1997 by W .B. Saunders Company.