SMO and cancer: In order to further complement our conclusions, we ran MD simulations of SMO and its naturally occurring cancer mutants R6.32 to H6.32 and W7.55 to L7.55 based on the crystal structure of human SMO in the absence of the extracellular CRD and without a crystallization scaffold in IL3 (PDB 4JKV; Supplementary Figure 8c–f).