8VEZ

De novo design apixaban-binding protein: apx1049

Summary for 8VEZ

• Entry DOI: 10.2210/pdb8vez/pdb
• Descriptor: De novo design apixaban-binding protein: apx1049, 1-(4-METHOXYPHENYL)-7-OXO-6-[4-(2-OXOPIPERIDIN-1-YL)PHENYL]-4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3,4-C]PYRIDINE-3-CARBOXAMIDE (3 entities in total)
• Functional Keywords: protein design, deep learning, small-molecule-binding, de novo design, apixaban, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 13557.74

Authors

Bera, A.K.,Lee, G.R.,Baker, D. (deposition date: 2023-12-20, release date: 2025-01-15, Last modification date: 2026-07-08)

Primary citation

Lee, G.R.,Pellock, S.J.,Norn, C.,Tischer, D.,Dauparas, J.,Anishchenko, I.,Mercer, J.A.M.,Kang, A.,Bera, A.K.,Nguyen, H.,Brackenbrough, E.,Sankaran, B.,Goreshnik, I.,Vafeados, D.,Roullier, N.,Han, H.L.,Coventry, B.,Haddox, H.K.,Liu, D.R.,Yeh, A.H.,Baker, D.
Small-molecule binding and sensing with a designed protein family.
Nat Commun, 17:-, 2026

PubMed Abstract: The de novo design of small-molecule-binding proteins holds great promise as a potential tool to develop sensors on-demand for arbitrary small molecules. Here we combine deep learning and physics-based methods to generate a family of proteins with diverse and designable pocket geometries, which we employ to computationally design binders for six small-molecule targets. Biophysical characterization of the designed binders reveals nanomolar to low micromolar binding affinities and atomic-level design accuracy. Additionally, we use a cortisol binder to design a chemically induced dimerization (CID) system that enables the construction of a biosensor for cortisol detection. The approach described here demonstrates the potential of the NTF2 fold and deep learning-based protein design in sensor development, paving the way for future platforms to design binders and sensors for small molecules across analytical, environmental, and biomedical applications.

PubMed: 41904144
DOI: 10.1038/s41467-026-70953-8

Experimental method

X-RAY DIFFRACTION (2.15 Å)