Noncanonical α/γ Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field.
J Phys Chem B
; 121(11): 2420-2433, 2017 03 23.
Article
en En
| MEDLINE
| ID: mdl-28290207
The sugar-phosphate backbone of RNA can exist in diverse rotameric substates, giving RNA molecules enormous conformational variability. The most frequent noncanonical backbone conformation in RNA is α/γ = t/t, which is derived from the canonical backbone by a crankshaft motion and largely preserves the standard geometry of the RNA duplex. A similar conformation also exists in DNA, where it has been extensively studied and shown to be involved in DNA-protein interactions. However, the function of the α/γ = t/t conformation in RNA is poorly understood. Here, we present molecular dynamics simulations of several prototypical RNA structures obtained from X-ray and NMR experiments, including canonical and mismatched RNA duplexes, UUCG and GAGA tetraloops, Loop E, the sarcin-ricin loop, a parallel guanine quadruplex, and a viral pseudoknot. The stability of various noncanonical α/γ backbone conformations was analyzed with two AMBER force fields, ff99bsc0χOL3 and ff99bsc0χOL3 with the recent εζOL1 and ßOL1 corrections for DNA. Although some α/γ substates were stable with seemingly well-described equilibria, many were unstable in our simulations. Notably, the most frequent noncanonical conformer α/γ = t/t was unstable in both tested force fields. Possible reasons for this instability are discussed. Our work reveals a potentially important artifact in RNA force fields and highlights a need for further force field refinement.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN
/
Conformación de Ácido Nucleico
Idioma:
En
Revista:
J Phys Chem B
Asunto de la revista:
QUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
República Checa
Pais de publicación:
Estados Unidos