8BL5

Crystal Structure of Sam0.2

Summary for 8BL5

• Entry DOI: 10.2210/pdb8bl5/pdb
• Descriptor: Sam0.2 (1 entity in total)
• Functional Keywords: protein design, vegf inhibitor, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 16722.89

Authors

Maksymenko, K.,ElGamacy, M.,Hartmann, M.D. (deposition date: 2022-11-09, release date: 2024-05-22, Last modification date: 2025-12-10)

Primary citation

Maksymenko, K.,Hatskovska, V.,Coles, M.,Aghaallaei, N.,Pashkovskaia, N.,Borbaran-Bravo, N.,Pilz, M.,Bucher, P.,Volz, M.,Pereira, J.,Hartmann, M.D.,Tabatabai, G.,Feucht, J.,Liebau, S.,Muller, P.,Lupas, A.N.,Skokowa, J.,ElGamacy, M.
A Complementarity-Based Approach to De Novo Binder Design.
Adv Sci, 12:e02015-e02015, 2025

PubMed Abstract: De novo design of binders capable of targeting arbitrarily selected epitopes remains a substantial challenge. Here, a generalizable computational strategy is presented to design site-specific protein binders, obviating steps of extensive empirical optimization or in vitro screening. The dock-and-design pipeline retrieves complementary scaffolds from a protein structure database to a given query epitope, where the scaffold is mutated to carve a binding site de novo. The docking step utilizes a novel fingerprint that greatly simplifies and accelerates the surface complementarity evaluation. As proof-of-concept, we designed protein binders to target three distinct epitopes on two different oncogenic targets; vascular endothelial growth factor (VEGF) and interleukin-7 receptor-α (IL-7Rα). Experimental characterization of only 24 candidates identified nanomolar binders against each of the target epitopes, where the binders belonged to five different folds. Several designs were active in vitro. Moreover, anti-VEGF designs showed tumor-inhibiting activity in vivo, highlighting their therapeutic potential.

PubMed: 40686280
DOI: 10.1002/advs.202502015

Experimental method

X-RAY DIFFRACTION (2.65 Å)