Hallucination of closed repeat proteins containing central pockets.
Nat Struct Mol Biol
; 30(11): 1755-1760, 2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37770718
ABSTRACT
In pseudocyclic proteins, such as TIM barrels, ß barrels, and some helical transmembrane channels, a single subunit is repeated in a cyclic pattern, giving rise to a central cavity that can serve as a pocket for ligand binding or enzymatic activity. Inspired by these proteins, we devised a deep-learning-based approach to broadly exploring the space of closed repeat proteins starting from only a specification of the repeat number and length. Biophysical data for 38 structurally diverse pseudocyclic designs produced in Escherichia coli are consistent with the design models, and the three crystal structures we were able to obtain are very close to the designed structures. Docking studies suggest the diversity of folds and central pockets provide effective starting points for designing small-molecule binders and enzymes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proteins
/
Hallucinations
Limits:
Humans
Language:
En
Journal:
Nat Struct Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos