AI and the World's Hard Problems · Bioengineering & synthetic biology · arXiv · 2026-10-26
Computational De Novo Design of Miniprotein Candidate Neutralizers Targeting the IL-23 Cytokine Subunit p19
Interleukin-23 drives inflammatory bowel disease and psoriasis, but published de novo miniprotein designs have targeted its receptor rather than the IL-23 cytokine itself. The authors computationally designed binders to the IL-23R-binding face of p19 and scored them with ipSAE; a conventional pipeline gave no reliable interface, while BindCraft produced 42 of 50 designs above ipSAE 0.60 (best 0.804). Five all-alpha-helical leads were proposed, but all results require experimental validation.