3dRNA: Building RNA 3D structure with improved template library

Abstract

Most of computational methods of building RNA tertiary structure are template-based. The template-based methods usually can give more accurate 3D structures due to the use of native 3D templates, but they cannot work if the 3D templates are not available. So, a more complete library of the native 3D templates is very important for this type of methods. 3dRNA is a template-based method for building RNA tertiary structure previously proposed by us. In this paper we report improved 3D template libraries of 3dRNA by using two different schemes that give two libraries 3dRNA_Lib1 and 3dRNA_Lib2. These libraries expand the original one by nearly ten times. Benchmark shows that they can significantly increase the accuracy of 3dRNA, especially in building complex and large RNA 3D structures.

Keywords: 3D template library; 3dRNA; RNA 3D structure prediction.

Fig. 1

Definition of SSEs in 3dRNA for an RNA (PDB id: 2GIS). Stems are shown in green, hairpin loops in blue, internal loops in yellow, bulge loop in grey, open loop in orange, and junction in red. (A) and (B) shows the difference between definitions of an SSE in (A) 3dRNA_Lib1 and in (B) 3dRNA_Lib2 when there are cases of a single base pair (helix with one base pair) (here 13–41 and 64–85). In 3dRNA_Lib1 the single base pair is opened before identifying SSE. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

The procedure of building 3D template library of 3dRNA.

Fig. 3

The flow of adding SSE 3D structures of an RNA (PDB id: 1Y26) to the template library. RNA 2D plots are generated using Forna .

Fig. 4

Statistics of different types of loops in 3dRNA_Oldlib (A) and 3dRNA_Lib1 (B). ‘nwj’ represents junctions containing at least 6 helices, ‘all’ represents the number of loops of all types in the template library, and ‘filter’ represents the number of loops that keeps one of the SSEs with identical sequences and secondary structures (pseudoknots are ignored).

Fig. 5

The relations between the lengths and RMSDs of the predictions for the RNAs in Test Set I. (A) The RMSDs of the RNAs under three different length ranges (len1, len2 and len3) when using “3dRNA_Lib1” with self-inclusion. The len1, len2 and len3 represent 0-500nt, 500-1000nt and 1000-5000nt, respectively. (B) The RMSDs of RNAs under five different length ranges (len1, len2, len3, len4 and len5) when using “3dRNA_Lib1” and “3dRNA_Lib2” with self-exclusion. The len1, len2, len3, len4 and len5 represent 0-50nt, 50-100nt, 100-500nt, 500-1000nt and 1000nt-5000nt, respectively. For each length range, the left and right boxes represent the RMSDs of the predictions of “3dRNA_Lib1” and “3dRNA_Lib2”, respectively.

Fig. 6

Comparison of the prediction accuracies (RMSDs) of 3dRNA using the new libraries with 3dRNA using old library and RNAComposer. (A) Comparison of the RMSDs of “3dRNA_Lib1” and “3dRNA_Lib2” with “3dRNA_Oldlib” for assembled structures. (B) and (C) Comparison of the RMSDs of “3dRNA_Lib1” and “3dRNA_Lib2” with “3dRNA_Oldlib” and RNAComposer for optimized structures. The lowest RMSD (B) and the mean RMSD (C) of the top 5 optimized structures of each RNA are used.

Fig. 7

Predicted and native 3D structures of a riboswitch (PDB id: 1FFZ). (A) The native (pink), assembled (green) and optimized (blue) structures by “3dRNA_Lib1”. (B) The native structure (pink), the assembled structure (green) by “3dRNA_Oldlib” and the optimized structure (red) by RNAComposer. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 8

2D and 3D Structures of (A) puzzle8, (B) puzzle13, (C) puzzle17 and (D) puzzle18 which are difficult to predict by “3dRNA_Lib1”. The pink color shows the experimentally determined structures, the green color shows the assembled structures of “3dRNA_Lib1”. The 2D and 3D structures are generated using Forna and PyMOL (http://www.pymol.org/), respectively. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 9

Running times of assembling RNA structures by 3dRNA.