Bioinformatický seminár

Tue 22 Nov. 2011, 17:20

Title: Flores et al. Predicting RNA structure by multiple template homology modeling
Speaker: Gábor Beke

Despite the importance of 3D structure to understand the myriad functions
of RNAs in cells, most RNA molecules remain out of reach of
crystallographic and NMR methods. However, certain structural information
such as base pairing and some tertiary contacts can be determined readily
for many RNAs by bioinformatics or relatively low cost experiments.
Further, because RNA structure is highly modular, it is possible to deduce
local 3D structure from the solved structures of evolutionarily related
RNAs or even unrelated RNAs that share the same module. RNABuilder is a
software package that generates model RNA structures by treating the
kinematics and forces at separate, multiple levels of resolution.
Kinematically, bonds in bases, certain stretches of residues, and some
entire molecules are rigid while other bonds remain flexible. Forces act
on the rigid bases and selected individual atoms. Here we use RNABuilder
to predict the structure of the 200-nucleotide Azoarcus group I intron by
homology modeling against fragments of the distantly-related Twort and
Tetrahymena group I introns and by incorporating base pairing forces where
necessary. In the absence of any information from the solved Azoarcus
intron crystal structure, the model accurately depicts the global
topology, secondary and tertiary connections, and gives an overall RMSD
value of 4.6 A relative to the crystal structure. The accuracy of the
model is even higher in the intron core (RMSD = 3.5 A), whereas deviations
are modestly larger for peripheral regions that differ more substantially
between the different introns. These results lay the groundwork for using
this approach for larger and more diverse group I introns, as well for
still larger RNAs and RNA-protein complexes such as group II introns and
the ribosomal subunits.