In silico evolution of nucleic acid-binding proteins from a nonfunctional scaffold.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
30
03
2021
accepted:
04
01
2022
pubmed:
26
2
2022
medline:
27
4
2022
entrez:
25
2
2022
Statut:
ppublish
Résumé
Directed evolution emulates the process of natural selection to produce proteins with improved or altered functions. These approaches have proven to be very powerful but are technically challenging and particularly time and resource intensive. To bypass these limitations, we constructed a system to perform the entire process of directed evolution in silico. We employed iterative computational cycles of mutation and evaluation to predict mutations that confer high-affinity binding activities for DNA and RNA to an initial de novo designed protein with no inherent function. Beneficial mutations revealed modes of nucleic acid recognition not previously observed in natural proteins, highlighting the ability of computational directed evolution to access new molecular functions. Furthermore, the process by which new functions were obtained closely resembles natural evolution and can provide insights into the contributions of mutation rate, population size and selective pressure on functionalization of macromolecules in nature.
Identifiants
pubmed: 35210620
doi: 10.1038/s41589-022-00967-y
pii: 10.1038/s41589-022-00967-y
doi:
Substances chimiques
Nucleic Acids
0
Proteins
0
RNA
63231-63-0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
403-411Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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