A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins.
PLoS Comput Biol
; 14(12): e1006393, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30507941
ABSTRACT
Intrinsically disordered proteins/regions (IDPs/IDRs) are prevalent in allosteric regulation. It was previously thought that intrinsic disorder is favorable for maximizing the allosteric coupling. Here, we propose a comprehensive ensemble model to compare the roles of both order-order transition and disorder-order transition in allosteric effect. It is revealed that the MWC pathway (order-order transition) has a higher probability than the EAM pathway (disorder-order transition) in allostery, suggesting a complicated role of IDPs/IDRs in regulatory proteins. In addition, an analytic formula for the maximal allosteric coupling response is obtained, which shows that too stable or too unstable state is unfavorable to endow allostery, and is thus helpful for rational design of allosteric drugs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Simulação de Dinâmica Molecular
/
Proteínas Intrinsicamente Desordenadas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article