Automated identification of RNA conformational motifs: theory and application to the HM LSU 23S rRNA

Abstract

We develop novel methods for recognizing and cataloging conformational states of RNA, and for discovering statistical rules governing those states. We focus on the conformation of the large ribosomal subunit from Haloarcula marismortui. The two approaches described here involve torsion matching and binning. Torsion matching is a pattern-recognition code which finds structural repetitions. Binning is a classification technique based on distributional models of the data. In comparing the results of the two methods we have tested the hypothesis that the conformation of a very large complex RNA molecule can be described accurately by a limited number of discrete conformational states. We identify and eliminate extraneous and redundant information without losing accuracy. We conclude, as expected, that four of the torsion angles contain the overwhelming bulk of the structural information. That information is not significantly compromised by binning the continuous torsional information into a limited number of discrete values. The correspondence between torsion matching and binning is 99% (per residue). Binning, however, does have several advantages. In particular, we demonstrate that the conformation of a large complex RNA molecule can be represented by a small alphabet. In addition, the binning method lends itself to a natural graphical representation using trees.

Figure 1

Ribonucleotide torsion angles used to specify conformation. The ribose pseudorotation phase angle (P) is not indicated.

Figure 2

Tetraloops. Stereoview of the superimposition of the 25 RNA fragments within the tetraloop family are shown here. Only backbone atoms were used for the superimposition. Only backbone atoms are shown. The atoms are colored using the CPK standard.

Figure 3

Plots of angle versus frequency of observation of the backbone and glycosidic torsion angles and the pseudorotation phase angle (P) of HM 23S rRNA. The symbols g+, a, and g– at the bottom of the graph refer to gauche+, anti and gauche–, respectively. The shaded regions indicate the binning limits for the four ‘conformational identifier’ torsion angles.

Figure 4

The tree representation of the conformation of HM 23S rRNA. The four different α branches are represented in A–D. The bin numbers correspond to branch numbers (indicated). The numbers in italics represent the populations of the binned states. Line widths are weighted by the logarithms of the populations. Dashed lines indicate a population of one.