Wow what a great resource - thanks Brian!

We think the consensus approach will allow the field to better model the OR family, especially if combined with the latest approaches in small molecule-protein complex prediction by methods like AF3. We are actively pursuing these now!

These structures, combined with mutagenesis studies in Hiro's group and extensive simulation work by Ning Ma and Vaidehi Nagarajan highlighted several unique properties of odorant recognition. The most baffling is that the receptor pockets are large, and odorants are quite flexible in the pocket.

So far, we had only seen how fish-like" odorant receptors recognize their odorants, which are typically water soluble. We really wanted to examine the much larger family of receptors that allow us to sense volatile odorants. Using the consensus strategy, we obtained several more structures.

Luckily Christian Billesboelle solved a structure of a native human OR, OR51E2, which we reported last year - www.nature.com/articles/s41.... This provided clear context for the consensus structure, and highlighted that the consensus structures are great mimics of the native structures.

Working with @scicadm.bsky.social, I was able to show that these constructs were highly tractable - students in my lab much more adept at cryoEM than I am helped me solve a structure of the first such receptor, OR51. We got this result, but were unsure what to make of it.

This started with a cold email to Hiro Matsunami because I was excited by their brilliant paper in PNAS (www.pnas.org/doi/10.1073/...) where they demonstrated that designing "consensus" receptors overcame the central challenge in expression that plagues the field.