Energy-based modeling in BioNetGen

Biochemical processes typically operate on molecular sites (domains, motifs, residues). In rule-based modeling languages such as BioNetGen (BNG), reactions driven by the same set of sites with the same rate law can be represented using a single reaction rule. This leads to compact model representations when sites behave independently, but not when a large number of sites interact cooperatively. Additionally, loops of reactions are constrained by detailed balance equations involving their rate constants, but these constraints have to be enforced manually when specifying rate laws for rules. Here, we introduce the energy-based BioNetGen specification (eBNG), in which models always satisfy detailed balance and cooperative interactions are compactly specified as free energy contributions. We demonstrate this approach using well-known models of molecular cooperativity, such as ligand-induced receptor dimerization and allosteric modulation.