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 journalArticlepeer-review

230 Scopus citations


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
Issue number6
StatePublished - Jun 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology


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