In this case only the vanilla Vina docking pose yields an accurate free energy estimate (-9.7 ± 0.7 kcal/mol c.f.-9.7 ± 0.2 for experiment), however, this starting structure is reversed in comparison to the pose predictions by all other docking protocols. This suggests that consistency in pose prediction among docking algorithms does not necessarily warrant accurate affinity estimation. Another example of this effect is the vanilla Vina protocol applied to the PTP1B system: more than 33% of the PTP1B vanilla Vina poses were reversed in comparison to other approaches (Fig ). Although, starting simulations with such poses deteriorates prediction accuracy, even in this case the overall ΔG accuracy is not significantly worse than for the rest of the docking protocols . These examples also highlight the sometimes unexpected insensitivity of the binding affinity predictions to the starting pose.