posted on 2016-04-22, 00:00authored byAnna Górska, Agnieszka Markowska-Zagrajek, Marcin Równicki, Joanna Trylska
We have designed
a protocol and server to aid in the search for
putative binding sites in 16S rRNA that could be targeted by peptide
nucleic acid oligomers. Various features of 16S rRNA were considered
to score its regions as potential targets for sequence-specific binding
that could result in inhibition of ribosome function. Specifically,
apart from the functional importance of a particular rRNA region,
we calculated its accessibility, flexibility, energetics of strand
invasion by an oligomer, as well as similarity to human rRNA. To determine
16S rRNA flexibility in the ribosome context, we performed all-atom
molecular dynamics simulations of the 30S subunit in explicit solvent.
We proposed a few 16S RNA target sites, and one of them was tested
experimentally to verify inhibition of bacterial growth by a peptide
nucleic acid oligomer.