Fig. 1.
Simulated response surfaces using the GPDI model. Combined effects (color gradient) were simulated of drugs A and B for Loewe Additivity (LA, a–f) and Bliss Independence (BI, g–q) on EC50 level (a–l) or Emax level (m–q); Mono drug effects were parameterized with EmaxA = EmaxB = 1, EC50A = EC50B = 50 µM, H A = H B = 4 leading to null interaction surface for LA (a), and BI (g); monodirectional interaction surfaces (b, c, h, i), were obtained if A as perpetrator increased (b, h), or decreased (c, i), the EC50 of B; bidirectional interactions (d–f, j–l), were obtained if both drugs displayed the perpetrator role on each other with a joint increase of the EC50 leading to antagonism (d, j), or decrease of the EC50 leading to synergy (e, k), bidirectional asymmetric interactions (b, d), were obtained if A decreased EC50B and B increased EC50A leading to concentration-dependent synergy or antagonism; the GPDI model approach within Bliss Independence is compatible with different Emax values for both drugs (m) and can describe effects of itself inactive allosteric modulators (n, o), buffering (p), and coalism of two inactive drugs (q). The parameters of the GPDI model to generate scenarios are presented in Supplementary Table 1