Because these scenarios are in conflict, we have employed a deterministic mathematical modelling strategy to explore the concentration-dependent effects of aBH3 and dBH3s alone or in combination, on the maximum rate of BAK activation. Our findings suggest that both the agonism and dissociation models reflect valid and potentially coexisting mechanisms for BAK activation, provided that strict constraints are applied. We have used dynamical systems analysis to explore the kinetics of mitochondrial BAK activation in the presence or absence of aBH3s, in order to address the question of how Fulvestrant efficiently dBH3s induce apoptosis at the level of the outer mitochondrial membrane. Mathematical modelling enables deeper insight and understanding of complex dynamic systems. However, there have been no attempts to date to model mitochondrial membrane resident BAK in the context of multiple PBPs nor multiple dBH3s, which are both LY2109761 inquirer biologically relevant. In silico modelling has been reported in relation to BAX, however these studies were limited to considerable simplification of the interactions between one PBP, aBH3 and BAX, and have attempted to incorporate both mitochondrial translocation of BAX/aBH3 and outer mitochondrial permeabilization events, both of which are poorly defined at the molecular level. Furthermore, BAX/BAK are resident in the endoplasmic reticulum as well as the mitochondrial compartment, and probably behave as interacting dynamical systems. For example, the BH3 only proteins BIK triggers ER BAK leading to ER-mitochondrial interactions and apoptosis. aBH3s, in order to address the question of how efficiently dBH3s induce apoptosis at the level of the outer mitochondrial membrane. Mathematical modelling enables deeper insight and understanding of complex dynamic systems. However, there have been no attempts to date to model mitochondrial membrane resident BAK in the context of multiple PBPs nor multiple dBH3s, which are both biologically relevant. In silico modelling has been reported in relation to BAX, however these studies were limited to considerable simplification of the interactions between one PBP, aBH3 and BAX, and have attempted to incorporate both mitochondrial translocation of BAX/aBH3 and outer mitochondrial permeabilization events, both of which are poorly defined at the molecular level. Furthermore, BAX/BAK are resident in the endoplasmic reticulum as well as the mitochondrial compartment, and probably behave as interacting dynamical systems. For example, the BH3 only proteins BIK triggers ER BAK leading to ER-mitochondrial interactions and apoptosis. We demonstrate that the within-membrane interactions of mitochondrial BCL-2 proteins and BH3 domains, although complex, are amenable to this mathematical modelling approach.