A molecular dynamics study of a miRNA:mRNA interaction |
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Authors: | Giulia Paciello Andrea Acquaviva Elisa Ficarra Marco Agostino Deriu Enrico Macii |
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Institution: | (1) Department of Control and Computer Engineering, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Turin, Italy;(2) Department of Mechanics, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Turin, Italy |
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Abstract: | In this paper we present a methodology to evaluate the binding free energy of a miRNA:mRNA complex through molecular dynamics
(MD)–thermodynamic integration (TI) simulations. We applied our method to the Caenorhabditis elegans let-7 miRNA:lin-41 mRNA complex—a validated miRNA:mRNA interaction—in order to estimate the energetic stability of the structure.
To make the miRNA:mRNA 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. |
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