Gandeeva Therapeutics, a biotech at the forefront of cryo-electron microscopy –driven drug design, and Zymeworks Inc a global biotechnology company, have partnered to visualize structures of antibody-antigen interfaces at high resolution.
While cryo-EM is now used routinely to determine structures of antibody complexes formed with compact and well-folded antigens, mapping antibody epitope footprints on small and flexible antigens remains highly challenging. In a new advance, Gandeeva scientists have determined the structure of a small and flexible antigen (< 20 kDa) bound to the Fab fragment of an antibody developed at Zymeworks. Of note, the team was able to visualize the nine amino acids that form the antibody-binding epitope at 2.6 Å resolution. The rest of the antigen is highly flexible and was not resolved in the reconstruction.
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“Knowledge of the precise interactions at the binding interface of these types of challenging targets is incredibly useful for us in selecting antibody leads and provides us with crucial insights for the optimization of biologics”, said Dr. Paul Moore, Chief Scientific Officer of Zymeworks.
“Our ability to obtain near-atomic resolution cryo-EM structures of the antibody binding epitope within flexible and structurally intractable proteins is a game-changer, especially in the context of accelerating design of AI-driven antibodies”, said Dr. Sriram Subramaniam, Founder and CEO of Gandeeva Therapeutics. “Experimental validation by high-resolution and high-throughput cryo-EM using Gandeeva’s platform provides exactly the kind of rapid feedback that is essential for testing and validating antibodies derived by immunization and by computational design.”
SOURCE: PRNewswire