iPARTS: an improved tool of pairwise alignment of RNA tertiary structures

Abstract

iPARTS is an improved web server for aligning two RNA 3D structures based on a structural alphabet (SA)-based approach. In particular, we first derive a Ramachandran-like diagram of RNAs by plotting nucleotides on a 2D axis using their two pseudo-torsion angles eta and . Next, we apply the affinity propagation clustering algorithm to this eta- plot to obtain an SA of 23-nt conformations. We finally use this SA to transform RNA 3D structures into 1D sequences of SA letters and continue to utilize classical sequence alignment methods to compare these 1D SA-encoded sequences and determine their structural similarities. iPARTS takes as input two RNA 3D structures in the PDB format and outputs their global alignment (for determining overall structural similarity), semiglobal alignments (for detecting structural motifs or substructures), local alignments (for finding locally similar substructures) and normalized local structural alignments (for identifying more similar local substructures without non-similar internal fragments), with graphical display that allows the user to visually view, rotate and enlarge the superposition of aligned RNA 3D structures. iPARTS is now available online at http://bioalgorithm.life.nctu.edu.tw/iPARTS/.

Figure 1.

(a) Six standard backbone torsion angles of α, β, γ, δ, ε and ζ and (b) two backbone pseudo-torsion angles of η and θ for a nucleotide (denoted by n), where η is defined by the atoms C4^′_n−1, P_n, C4^′_n and P_n+1, while θ is defined by P_n, C4^′_n, P_n+1 and C4^′_n+1.

Figure 2.

The ROC curves of iPARTS and PARTS on data set #1 based on (a) native alignment score, where the AUC values of iPARTS and PARTS are 0.87 and 0.81, respectively, and (b) based on SAS score, where the AUC values of iPARTS and PARTS are 0.86 and 0.85, respectively.

Figure 3.

(a) ROC curves based on native alignment score, where the AUC values of ARTS, LaJolla and iPARTS are 0.65, 0.74 and 0.91, respectively. (b) ROC curves based on SAS score, where the AUC values of ARTS, LaJolla and iPARTS are 0.83, 0.83 and 0.91, respectively.

Figure 4.

The ROC curves when testing our iPARTS for its capability of function assignment using (a) the FSCOR data set, where the AUC values for d = 0 and d ≤ 2 are 0.72 and 0.92, respectively, and (b) the R-FSCOR and T-FSCOR data sets, where the AUC values for d = 0 and d ≤ 2 are 0.77 and 0.90, respectively.

Figure 5.

Superposition display of iPARTS global alignment between two 16S rRNA 3D structures of T. thermophilus (PDB ID: 1J5E, chain ID: A, length: 1513 bp) colored green and E. coli (PDB ID: 2AVY, chain ID: A, length: 1530 bp) colored orange with an RMSD of 7.491 Å.