RNA molecules are key players in numerous cellular processes and are characterized by a complex relationship between structure, dynamics, and function. Despite their apparent simplicity, RNA oligonucleotides are very flexible molecules, and understanding their internal dynamics is particularly challenging using experimental data alone. We show how to reconstruct the conformational ensemble of four RNA tetranucleotides by combining atomistic molecular dynamics simulationswith nuclear magnetic resonance spectroscopy data. The goal is achieved by reweighting simulations using a maximum entropy/Bayesian approach. In this way, we overcome problems of current simulation methods, as well as in interpreting ensemble- and time-averaged experimental data. We determine the populations of different conformational states by considering several nuclear magnetic resonance parameters and point toward properties that are not captured by state-of-the-art molecular force fields. Although our approach is applied on a set of model systems, it is fully general and may be used to study the conformational dynamics of flexible biomolecules and to detect inaccuracies in molecular dynamics force fields.

Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations / Bottaro, Sandro; Bussi, Giovanni; Kennedy, Scott D.; Turner, Douglas H.; Lindorff-Larsen, Kresten. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 4:5(2018), p. eaar8521. [10.1126/sciadv.aar8521]

Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations

Bottaro, Sandro
;
Bussi, Giovanni;
2018

Abstract

RNA molecules are key players in numerous cellular processes and are characterized by a complex relationship between structure, dynamics, and function. Despite their apparent simplicity, RNA oligonucleotides are very flexible molecules, and understanding their internal dynamics is particularly challenging using experimental data alone. We show how to reconstruct the conformational ensemble of four RNA tetranucleotides by combining atomistic molecular dynamics simulationswith nuclear magnetic resonance spectroscopy data. The goal is achieved by reweighting simulations using a maximum entropy/Bayesian approach. In this way, we overcome problems of current simulation methods, as well as in interpreting ensemble- and time-averaged experimental data. We determine the populations of different conformational states by considering several nuclear magnetic resonance parameters and point toward properties that are not captured by state-of-the-art molecular force fields. Although our approach is applied on a set of model systems, it is fully general and may be used to study the conformational dynamics of flexible biomolecules and to detect inaccuracies in molecular dynamics force fields.
4
5
eaar8521
http://doi.org/10.1126/sciadv.aar8521
http://advances.sciencemag.org/content/4/5/eaar8521/tab-pdf
Bottaro, Sandro; Bussi, Giovanni; Kennedy, Scott D.; Turner, Douglas H.; Lindorff-Larsen, Kresten
File in questo prodotto:
File Dimensione Formato  
eaar8521.full.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 1.03 MB
Formato Adobe PDF
1.03 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11767/84994
Citazioni
  • ???jsp.display-item.citation.pmc??? 21
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 62
social impact