In the tubulin study, F04 (purple) and F36 (orange) inspired Todalam-4 (sky-blue: crystal, green: predicted). The aminothiazole ring is flipped between F04 and todalam-4 by design. A constructive observation of this derivative is that the N-benzyl is rotated in the crystal relative to F36 possibly to attain a T-shaped pi bond, a dipolemomentum-driven configuration, which is not modelled in classical mechanics forcefields such as that employed by Rosetta.