Bayesian reweighting of biomolecular structural ensembles using heterogeneous cryo-EM maps with the cryoENsemble method.
Sci Rep
; 14(1): 18149, 2024 08 05.
Article
em En
| MEDLINE
| ID: mdl-39103467
ABSTRACT
Cryogenic electron microscopy (cryo-EM) has emerged as a powerful method for the determination of structures of complex biological molecules. The accurate characterisation of the dynamics of such systems, however, remains a challenge. To address this problem, we introduce cryoENsemble, a method that applies Bayesian reweighting to conformational ensembles derived from molecular dynamics simulations to improve their agreement with cryo-EM data, thus enabling the extraction of dynamics information. We illustrate the use of cryoENsemble to determine the dynamics of the ribosome-bound state of the co-translational chaperone trigger factor (TF). We also show that cryoENsemble can assist with the interpretation of low-resolution, noisy or unaccounted regions of cryo-EM maps. Notably, we are able to link an unaccounted part of the cryo-EM map to the presence of another protein (methionine aminopeptidase, or MetAP), rather than to the dynamics of TF, and model its TF-bound state. Based on these results, we anticipate that cryoENsemble will find use for challenging heterogeneous cryo-EM maps for biomolecular systems encompassing dynamic components.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Teorema de Bayes
/
Microscopia Crioeletrônica
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Simulação de Dinâmica Molecular
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2024
Tipo de documento:
Article