A molecular dynamics study of a miRNA:mRNA interaction.
J Mol Model
; 17(11): 2895-906, 2011 Nov.
Article
en En
| MEDLINE
| ID: mdl-21318233
ABSTRACT
In this paper we present a methodology to evaluate the binding free energy of a miRNAmRNA complex through molecular dynamics (MD)-thermodynamic integration (TI) simulations. We applied our method to the Caenorhabditis elegans let-7 miRNAlin-41 mRNA complex-a validated miRNAmRNA interaction-in order to estimate the energetic stability of the structure. To make the miRNAmRNA simulation possible and realistic, the methodology introduces specific solutions to overcome some of the general challenges of nucleic acid simulations and binding free energy computations that have been discussed widely in many previous research reports. The main features of the proposed methodology are (1) positioning of the restraints imposed on the simulations in order to guarantee complex stability; (2) optimal sampling of the phase space to achieve satisfactory accuracy in the binding energy value; (3) determination of a suitable trade-off between computational costs and accuracy of binding free energy computation by the assessment of the scalability characteristics of the parallel simulations required for the TI. The experiments carried out demonstrate that MD simulations are a viable strategy for the study of miRNA binding characteristics, opening the way to the development of new computational target prediction methods based on three-dimensional structure information.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
MicroARNs
/
Simulación de Dinámica Molecular
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Mol Model
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2011
Tipo del documento:
Article