Improving sampling of crystallographic disorder in ensemble refinement.
Acta Crystallogr D Struct Biol
; 77(Pt 11): 1357-1364, 2021 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-34726164
Ensemble refinement, the application of molecular dynamics to crystallographic refinement, explicitly models the disorder inherent in macromolecular structures. These ensemble models have been shown to produce more accurate structures than traditional single-model structures. However, suboptimal sampling of the molecular-dynamics simulation and modelling of crystallographic disorder has limited the utility of the method, and can lead to unphysical and strained models. Here, two improvements to the ensemble refinement method implemented within Phenix are presented: DEN restraints, which guide the local sampling of conformations and allow a more robust exploration of local conformational landscapes, and ECHT disorder models, which allow the selection of more physically meaningful and effective disorder models for parameterizing the continuous disorder components within a crystal. These improvements lead to more consistent and physically interpretable simulations of macromolecules in crystals, and allow structural heterogeneity and disorder to be systematically explored on different scales. The new approach is demonstrated on several case studies and the SARS-CoV-2 main protease, and demonstrates how the choice of disorder model affects the type of disorder that is sampled by the restrained molecular-dynamics simulation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación de Dinámica Molecular
/
Proteasas 3C de Coronavirus
/
SARS-CoV-2
Límite:
Humans
Idioma:
En
Revista:
Acta Crystallogr D Struct Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Estados Unidos