Figure 3.

IL17-macrocycle interaction. A: An artificial macrocycle binding into a grove in the IL17A dimer interface (PDB ID 5HI4). B: 2D structure of macrocycle. C–E: Close-up view of two different macrocycle– receptor interacting regions. D: A spirocyclopentyl group hot spot undergoing multiple hydrophobic interactions with a receptor lysine, leucine, and glutamine. E: Macrocycle–receptor interaction overview, including hydrogen bindings, π, and hydrophobic interactions. F: Atomic hot spots of the macrocycle according to their contribution to the binding to the IL17 receptor. It was calculated using scorpion software and the color code is rendered according to their contribution to the energy, the interaction ranging from grey (minor contribution) to red (major contribution).⁶