Prospective docking of large libraries against unrefined AlphaFold2 (AF2) models of the σ2 and 5‑HT2A receptors yielded hit rates and affinities similar to those from experimental structures, and cryo‑EM of a potent 5‑HT2A ligand showed residue accommodations resembling the AF2 prediction. This demonstrates that AF2 models can sample alternative low‑energy conformations relevant for ligand discovery, extending the utility of structure‑based drug design.
- Published
- Journal
- Science
- Authors
- Lyu, J., Kapolka, N., Gumpper, R., Alon, A., Wang, L., Jain, M. K., Barros-Álvarez, X., Sakamoto, K., Kim, Y., DiBerto, J., Kim, K., Glenn, I. S., Tummino, T. A., Huang, S., Irwin, J. J., Tarkhanova, O. O., Moroz, Y., Skiniotis, G., Kruse, A. C., Shoichet, B. K., Roth, B. L.