However, for the acid and amine bond-level descriptors Sterimol L, B1, and B5 values, the models obtain varied accuracies. This can be partially explained by the pronounced directional and conformational dependence of these descriptors. Because the GNNs employ 2D molecular representations, they may be less adept at capturing conformational-and directionality-based information to which Sterimol descriptors are acutely sensitive. Hence, significant differences in Sterimol L, B1, and B5 values were observed, even within Boltzmannaveraged, minimum, maximum, and lowest energy conformer properties for a single descriptor.