GENERALIST: A latent space based generative model for protein sequence families.
PLoS Comput Biol
; 19(11): e1011655, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-38011273
ABSTRACT
Generative models of protein sequence families are an important tool in the repertoire of protein scientists and engineers alike. However, state-of-the-art generative approaches face inference, accuracy, and overfitting- related obstacles when modeling moderately sized to large proteins and/or protein families with low sequence coverage. Here, we present a simple to learn, tunable, and accurate generative model, GENERALIST GENERAtive nonLInear tenSor-factorizaTion for protein sequences. GENERALIST accurately captures several high order summary statistics of amino acid covariation. GENERALIST also predicts conservative local optimal sequences which are likely to fold in stable 3D structure. Importantly, unlike current methods, the density of sequences in GENERALIST-modeled sequence ensembles closely resembles the corresponding natural ensembles. Finally, GENERALIST embeds protein sequences in an informative latent space. GENERALIST will be an important tool to study protein sequence variability.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Aminoácidos
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos