primaryodors
commented
9 months ago Some of the structures have been released.
https://www.rcsb.org/structure/8HTG https://www.rcsb.org/structure/8HTI https://www.rcsb.org/structure/8J46
Still waiting on: https://www.rcsb.org/structure/8WW7
https://doi.org/10.1038/s41467-023-43983-9
The activation mechanism of OR52 receptors has been elucidated, using cryo-EM of a consensus protein based on the OR52 family. The researchers did not only determine the agonist bound structure, but also the structure of the inactive (apo) state. It is implied that the new experimental models may be sufficient for calculating predicted agonist activity of odorants on possibly the entire OR52 family.
The following RCSB models will be important for OR52 predictions: 8HTG, 8HTI, 8J46, 8WW7. The structures have not been released yet at the time of this post.
Since the experimental apo state differs from the AlphaFold models of the OR52 receptors, it will be necessary to create apo models of all OR52 proteins. These may be derived from the AF models by translating and rotating helices to match the cryo-EM apo model, or perhaps the side chains of the AF models can be pasted onto the backbone of the cryo-EM model. The new apo models should be checked for internal clashes and their helices' positions adjusted accordingly.
A parallel set of active models shall be made, using the same methodology as for the apo models, but with the cryo-EM agonist bound model as the template. Predictions can then be run against the apo vs. active models just as existing predictions that currently use the AF model as the inactive state; ligands that favor docking inside the apo model would favor the inactive state of the receptor.