Back

Computational design of microbial and animal rhodopsin soluble analogues

Hilditch, A.;Goverde, C.;Gasilova, N.;Warrelmann, S.;Goldbach, N.;Wachtveitl, J.;Menin, L.;Correia, B.

2026-06-29 Synthetic Biology
10.64898/2026.06.27.734960 bioRxiv
Show abstract

The computational design of soluble analogues of membrane proteins has unlocked exciting opportunities for the integration of unique membrane protein functions into soluble proteins. Here, we use AF2seq to generate accurate soluble analogues of both animal and microbial rhodopsins, based on the membrane GPCR topology, and the microbial rhodopsin transmembrane fold. We characterize the analogues and demonstrate that they are well-folded and highly thermostable. Furthermore, they exhibit the expected red shift characteristic of retinal binding. Top-down mass spectrometry confirms the placement of retinal covalent attachment, while X-ray crystallography validates the structural fidelity of the microbial rhodopsin analogue. Notably, the microbial rhodopsin analogue retains the primary reaction of the retinal photocycle, closely matching that of the native membrane protein. Overall, this work advances the possibility to transfer unique membrane protein functions, such as retinal photoswitching, into the soluble proteome.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.