Undersampling and the inference of coevolution in proteins.
Cell Syst
; 14(3): 210-219.e7, 2023 03 15.
Article
en En
| MEDLINE
| ID: mdl-36693377
ABSTRACT
Protein structure, function, and evolution depend on local and collective epistatic interactions between amino acids. A powerful approach to defining these interactions is to construct models of couplings between amino acids that reproduce the empirical statistics (frequencies and correlations) observed in sequences comprising a protein family. The top couplings are then interpreted. Here, we show that as currently implemented, this inference unequally represents epistatic interactions, a problem that fundamentally arises from limited sampling of sequences in the context of distinct scales at which epistasis occurs in proteins. We show that these issues explain the ability of current approaches to predict tertiary contacts between amino acids and the inability to obviously expose larger networks of functionally relevant, collectively evolving residues called sectors. This work provides a necessary foundation for more deeply understanding and improving evolution-based models of proteins.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas
/
Aminoácidos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Syst
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos