SE Neue Entwicklungen in der RNA Bioinformatik
270151 SE; Peter F. Stadler
Topic
Most, or maybe all, RNAs are not "naked" in the cell, but bound by a
plethora of protein. Our goal is to understand what this does to RNA
structure, to protein binding sites, and to the concentration(s) of
(competing) proteins.
As background material have a look e.g. at
Interplay between single-stranded binding proteins on RNA secondary structure.
Lin YH, Bundschuh R.
Phys Rev E Stat Nonlin Soft Matter Phys. 2013 Nov;88(5):052707.
and
Modeling the interplay of single-stranded binding proteins and nucleic
acid secondary structure.
Forties RA, Bundschuh R.
Bioinformatics. 2010 Jan 1;26(1):61-7.
We will assume that we have a set of binding site sequence together with a
preference for a sondary structure context, as derived e.g. with Backofena's
graphprot.
In essence this yields propensities for the binding of a particular protein
to RNA structures as a "knowledge based potential", which we can assume to
be related by an unknown affine transformation E = a*P + b,
where P is the log-odds score for binding from the data.
On the other hand we know how to compute genome-wide partition functions
with RNAplfold on a genome wide scale. With Ronny's new and cool
constraint handling machinery we can constrain binding sites to their
preferred binding conformation and thus obtain the energy necessary to
expose a binding site.
Task 1 Find out how we can get the binding energies for all sites
and at least an approximation for the interactions between close-by sites
without the (infeasible) computation of all possible occupancy patterns.
Task 2 We can safely assume that we also have RNA expression data.
So we also want to model the concentration dependence of binding site
occupancy.
Task 3 How can we use our insights to e.g. identify relevant
clusters of binding sites? Can we see protein-concentration dependent
switches in RNA structure that lead to global effects
Task 4 How does this look like if we have two (or more) proteins
with non-overlapping (and overlapping) binding sites. Is there any evidence
for cooperative behavior? How would this look like.