As a simple but illustrative example of the model construction process, we present a small biochemical model of the first few steps of ICL detection and repair by the FA/BRCA pathway (58, 59). During DNA replication, the presence of an ICL causes the replication fork to stall. This stressed fork is detected by the protein FANCM, which binds to the branched DNA structure caused by replication fork arrest and recruits the FA “core complex” to the damage site (Fig. 5A). The FA core complex is composed of three protein subcomplexes, each of which is composed of three proteins (Fig. 5B): AG20 is a complex of the proteins FANCA, FANCG, and FAAP20 (FA core complex associated protein 20); BL100 is a complex of FANCB, FANCL, and FAAP100; and CEF is a complex of FANCC, FANCE, and FANCF. For simplicity, we have chosen to represent in the model each of these subcomplexes as distinct molecular species that reversibly bind to each other to form the FA core complex. The complete computational model includes these subcomplex binding reactions, the binding of FANCM to the ICL, and binding of the FA core complex to ICL-bound FANCM (Fig. 5C). By defining parameter values for the rates of each of these individual reactions, the model becomes executable, i.e., the populations (or concentrations) of the constituent species can be simulated over time (Fig. 5D). In this way, hypotheses regarding the effects of mutations (changing parameter values) and/or adding external perturbagens (e.g., drugs) can be explored in silico.