Binding-and-Folding Recognition of an Intrinsically Disordered Protein Using Online Learning Molecular Dynamics.
J Chem Theory Comput
; 19(13): 3817-3824, 2023 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-37341654
ABSTRACT
Intrinsically disordered proteins participate in many biological processes by folding upon binding to other proteins. However, coupled folding and binding processes are not well understood from an atomistic point of view. One of the main questions is whether folding occurs prior to or after binding. Here we use a novel, unbiased, high-throughput adaptive sampling approach to reconstruct the binding and folding between the disordered transactivation domain of c-Myb and the KIX domain of the CREB-binding protein. The reconstructed long-term dynamical process highlights the binding of a short stretch of amino acids on c-Myb as a folded α-helix. Leucine residues, especially Leu298-Leu302, establish initial native contacts that prime the binding and folding of the rest of the peptide, with a mixture of conformational selection on the N-terminal region with an induced fit of the C-terminal.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Educação a Distância
/
Proteínas Intrinsicamente Desordenadas
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article