Exploiting conformational dynamics to modulate the function of designed proteins.
NMR spectroscopy
chemical exchange saturation transfer
conformational dynamics
ligand binding
protein design
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
02 05 2023
02 05 2023
Historique:
medline:
26
4
2023
pubmed:
24
4
2023
entrez:
24
04
2023
Statut:
ppublish
Résumé
With the recent success in calculating protein structures from amino acid sequences using artificial intelligence-based algorithms, an important next step is to decipher how dynamics is encoded by the primary protein sequence so as to better predict function. Such dynamics information is critical for protein design, where strategies could then focus not only on sequences that fold into particular structures that perform a given task, but would also include low-lying excited protein states that could influence the function of the designed protein. Herein, we illustrate the importance of dynamics in modulating the function of C34, a designed α/β protein that captures β-strands of target ligands and is a member of a family of proteins designed to sequester β-strands and β hairpins of aggregation-prone molecules that lead to a variety of pathologies. Using a strategy to "see" regions of
Identifiants
pubmed: 37094170
doi: 10.1073/pnas.2303149120
pmc: PMC10161014
doi:
Substances chimiques
Proteins
0
Peptides
0
Ligands
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2303149120Subventions
Organisme : CIHR
ID : FDN-503573
Pays : Canada
Organisme : CIHR
ID : FDN-455908
Pays : Canada
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