American Chemical Society, Journal of Physical Chemistry B (Soft Condensed Matter and Biophysical Chemistry), 42(114), p. 13497-13506, 2010
DOI: 10.1021/jp104926t
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The accurate prediction of an RNAs three dimensional structure from its “primary structure” will have a tremendous influence on the experimental design and its interpretation, and ultimately our understanding of the many functions of RNA. This paper presents a general coarse-grained (CG) potential for modeling RNA 3-D structures. Each nucleotide is represented by five pseudo atoms, two for the backbone (one for the phosphate and another for the sugar), and three for the base to represent base-stacking interactions. The CG potential has been parameterized from statistical analysis of 688 RNA experimental structures. Molecular dynamic simulations of 15 RNA molecules with the length of 12 to 27 nucleotides have been performed using the CG potential, with performance comparable to that from all-atom simulations. For ~75% of systems tested, simulated annealing led to native-like structures at least once out of multiple repeated runs. Furthermore, with weak distance restraints based on the knowledge of three to five canonical Watson-Crick pairs, all 15 RNAs tested are successfully folded to within 6.5 Å of native structures using the CG potential and simulated annealing. The results reveal that with a limited secondary structure model, the current CG potential can reliably predict the 3-D structures for small RNA molecules. We also explored an all-atom force field to construct atomic structures from the CG simulations.