Nonequilibrium Modeling of the Elementary Step in PDZ3 Allosteric Communication.
J Phys Chem Lett
; 13(42): 9862-9868, 2022 Oct 27.
Article
en En
| MEDLINE
| ID: mdl-36251493
ABSTRACT
While allostery is of paramount importance for protein signaling and regulation, the underlying dynamical process of allosteric communication is not well understood. The PDZ3 domain represents a prime example of an allosteric single-domain protein, as it features a well-established long-range coupling between the C-terminal α3-helix and ligand binding. In an intriguing experiment, Hamm and co-workers employed photoswitching of the α3-helix to initiate a conformational change of PDZ3 that propagates from the C-terminus to the bound ligand within 200 ns. Performing extensive nonequilibrium molecular dynamics simulations, the modeling of the experiment reproduces the measured time scales and reveals a detailed picture of the allosteric communication in PDZ3. In particular, a correlation analysis identifies a network of contacts connecting the α3-helix and the core of the protein, which move in a concerted manner. Representing a one-step process and involving direct α3-ligand contacts, this cooperative transition is considered as the elementary step in the propagation of conformational change.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dominios PDZ
/
Simulación de Dinámica Molecular
Límite:
Humans
Idioma:
En
Revista:
J Phys Chem Lett
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania