Ab initio RNA folding by discrete molecular dynamics: From structure prediction to folding mechanisms

Feng Ding, Shantanu Sharma, Poornima Chalasani, Vadim V. Demidov, Natalia E. Broude, Nikolay V. Dokholyan

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

RNA molecules with novel functions have revived interest in the accurate prediction of RNA three-dimensional (3D) structure and folding dynamics. However, existing methods are inefficient in automated 3D structure prediction. Here, we report a robust computational approach for rapid folding of RNA molecules. We develop a simplified RNA model for discrete molecular dynamics (DMD) simulations, incorporating base-pairing and base-stacking interactions. We demonstrate correct folding of 150 structurally diverse RNA sequences. The majority of DMD-predicted 3D structures have <4̊ A deviations from experimental structures. The secondary structures corresponding to the predicted 3D structures consist of 94% native base-pair interactions. Folding thermodynamics and kinetics of tRNAPhe, pseudoknots, and mRNA fragments in DMD simulations are in agreement with previous experimental findings. Folding of RNA molecules features transient, non-native conformations, suggesting nonhierarchical RNA folding. Our method allows rapid conformational sampling of RNA folding, with computational time increasing linearly with RNA length. We envision this approach as a promising tool for RNA structural and functional analyses. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)1164-1173
Number of pages10
JournalRNA
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2008

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RNA Folding
Molecular Dynamics Simulation
RNA
Base Pairing
RNA, Transfer, Phe
Thermodynamics
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Cite this

Ding, Feng ; Sharma, Shantanu ; Chalasani, Poornima ; Demidov, Vadim V. ; Broude, Natalia E. ; Dokholyan, Nikolay V. / Ab initio RNA folding by discrete molecular dynamics : From structure prediction to folding mechanisms. In: RNA. 2008 ; Vol. 14, No. 6. pp. 1164-1173.
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Ab initio RNA folding by discrete molecular dynamics : From structure prediction to folding mechanisms. / Ding, Feng; Sharma, Shantanu; Chalasani, Poornima; Demidov, Vadim V.; Broude, Natalia E.; Dokholyan, Nikolay V.

In: RNA, Vol. 14, No. 6, 01.06.2008, p. 1164-1173.

Research output: Contribution to journalArticle

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