Unraveling Mg2+-RNA binding with atomistic molecular dynamics.
RNA
; 23(5): 628-638, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-28148825
ABSTRACT
Interaction with divalent cations is of paramount importance for RNA structural stability and function. We report here a detailed molecular dynamics study of all the possible binding sites for Mg2+ on an RNA duplex, including both direct (inner sphere) and indirect (outer sphere) binding. In order to tackle sampling issues, we develop a modified version of bias-exchange metadynamics, which allows us to simultaneously compute affinities with previously unreported statistical accuracy. Results correctly reproduce trends observed in crystallographic databases. Based on this, we simulate a carefully chosen set of models that allows us to quantify the effects of competition with monovalent cations, RNA flexibility, and RNA hybridization. Our simulations reproduce the decrease and increase of Mg2+ affinity due to ion competition and hybridization, respectively, and predict that RNA flexibility has a site-dependent effect. This suggests a nontrivial interplay between RNA conformational entropy and divalent cation binding.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA de Cadeia Dupla
/
Magnésio
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
RNA
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália