Allosteric mechanism of the circadian protein Vivid resolved through Markov state model and machine learning analysis.
PLoS Comput Biol
; 15(2): e1006801, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30779735
ABSTRACT
The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an atomistic allosteric mechanism leading to the discovery of the unexpected importance of A'α/Aß and previously overlooked Eα/Fα loops in the conformational change. This approach could be applicable to other allosteric proteins in general to provide interpretable atomistic representations of their otherwise elusive allosteric mechanisms.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Fúngicas
/
Biologia Computacional
/
Regulação Alostérica
Tipo de estudo:
Health_economic_evaluation
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos