The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement.

Empirical corrections to the Amber RNA force field with Target Metadynamics / Gil Ley, Alejandro; Bottaro, Sandro; Bussi, Giovanni. - In: JOURNAL OF CHEMICAL THEORY AND COMPUTATION. - ISSN 1549-9618. - 12:6(2016), pp. 2790-2798. [10.1021/acs.jctc.6b00299]

Empirical corrections to the Amber RNA force field with Target Metadynamics

Gil Ley, Alejandro;Bottaro, Sandro;Bussi, Giovanni
2016-01-01

Abstract

The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement.
2016
12
6
2790
2798
10.1021/acs.jctc.6b00299
https://arxiv.org/abs/1605.00934
http://cdsads.u-strasbg.fr/abs/2016arXiv160500934G
Gil Ley, Alejandro; Bottaro, Sandro; Bussi, Giovanni
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/11774
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