On Constructing Thermodynamically Consistent Parametrizations of Kinetic Models

Experimental construction of biochemical reaction systems that model cellular behavior often leads to kinetic parameter values that do not satisfy important thermodynamic constraints, thus resulting in models that are not physically realizable. In this paper, we propose a method that takes thermodynamically infeasible published kinetic parameter values and recomputes a new set of thermodynamically consistent values. The method is based on formulating and implementing an appropriate constrained optimization problem by assuming that the molecular dynamics produced by the published values are “noisy” versions of the corresponding dynamics produced by the thermodynamically consistent “true” values.