Compartmental rule-based modeling of biochemical systems

Rule-based modeling is an approach to modeling biochemical kinetics in which proteins and other biological components are modeled as structured objects and their interactions are governed by rules that specify the conditions under which reactions occur. BioNetGen is an open-source platform that provides a simple yet expressive language for rule-based modeling (BNGL). In this paper we describe compartmental BNGL (cBNGL), which extends BNGL to enable explicit modeling of the compartmental organization of the cell and its effects on system dynamics. We show that by making localization a queryable attribute of both molecules and species and introducing appropriate volumetric scaling of reaction rates, the effects of compartmentalization can be naturally modeled using rules. These properties enable the construction of new rule semantics that include both universal rules, those defining interactions that can take place in any compartment in the system, and transport rules, which enable movement of molecular complexes between compartments.