Mechanistic Modeling of Biochemical Systems Without a Priori Parameter Values Using the Design Space Toolbox v.3.0

Abstract

Mechanistic models of biochemical systems provide a rigorous description of biological phenomena. They are indispensable to elucidate biological design principles. To date, mathematical analysis and characterization of these models remain a challenging endeavor. Here, we introduce the Design Space Toolbox v.3.0 (DST3), a software implementation of the Design Space formalism that enables mechanistic modeling of biological processes without requiring previous knowledge of the parameter values involved. This is achieved by making use of a phenotype-centric modeling approach, in which the system is first decomposed into a series of biochemical phenotypes. Parameter values realizing phenotypes of interest are predicted in a second step. DST3 represents the most generally applicable implementation of the Design Space formalism and offers unique advantages over earlier versions. By expanding the Design Space formalism and streamlining its distribution, DST3 represents a valuable tool for elucidating biological design principles and designing novel synthetic circuits.

Keywords: kinetic parameters, predictive modeling, global analysis, system design principles