Expanding the space of protein geometries by computational design of de novo fold families.
Science
; 369(6507): 1132-1136, 2020 08 28.
Article
in En
| MEDLINE
| ID: mdl-32855341
ABSTRACT
Naturally occurring proteins vary the precise geometries of structural elements to create distinct shapes optimal for function. We present a computational design method, loop-helix-loop unit combinatorial sampling (LUCS), that mimics nature's ability to create families of proteins with the same overall fold but precisely tunable geometries. Through near-exhaustive sampling of loop-helix-loop elements, LUCS generates highly diverse geometries encompassing those found in nature but also surpassing known structure space. Biophysical characterization showed that 17 (38%) of 45 tested LUCS designs encompassing two different structural topologies were well folded, including 16 with designed non-native geometries. Four experimentally solved structures closely matched the designs. LUCS greatly expands the designable structure space and offers a new paradigm for designing proteins with tunable geometries that may be customizable for novel functions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Engineering
/
Protein Structure, Secondary
/
Protein Folding
/
Computer-Aided Design
Language:
En
Journal:
Science
Year:
2020
Type:
Article