RNAdesign-0.1.1.0: README.md

RNAdesign
=========

The RNAdesign program solves the multi-target RNA sequence design problem. You
can give one or more structural targets for which a single compatible sequence
is designed.

PAPER
=====

Christian Hoener zu Siederdissen, Stefan Hammer, Ingrid Abfalter, Ivo L. Hofacker, Christoph Flamm, Peter F. Stadler.
Computational Design of RNAs with Complex Energy Landscapes.
2013. Biopolymers. 99, no. 12. 99. 1124–36. http://dx.doi.org/10.1002/bip.22337.

Contact
=======

choener@tbi.univie.ac.at



HOW TO USE RNAdesign
====================

RNAdesign designs RNA sequences given one or more structural targets. The
program offers a variety of optimization functions that each can be used to
optimize candidate sequence towards a certain goal, say, minimal ensemble
defect or small energetic distance to another target structure.


RNAdesign input
---------------

Structural targets are given via stdin, preferably via an input file. Below is
a the small tri-stable from our paper, which you should then pipe to RNAdesign:
"echo tri-stable.dat | RNAdesign"

"cat tri-stable.dat:"

 # a tri-stable example target. (optional comment)
 ((((....))))....((((....))))........
 ........((((....((((....))))....))))
 ((((((((....))))((((....))))....))))
 # below follows a simple (and optional) sequence constraint.
 CKNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNB

The input may contain many comments lines, starting with a hash "#" and at most
one sequence constraint line. All of these lines are optional, except of course
for the structural constraints.


Optimization functions
----------------------

Depending on the actual design you are looking for, you'll want to modify the
optimization function. Below, the different options available are detailed. By
giving a complex "--optfun", many different design goals can be tried.

A good optimization goal is (as an example for three targets):

--optfun "eos(1)+eos(2)+eos(3) - 3 * gibbs + 1 * ((eos(1)-eos(2))^2 + (eos(1)-eos(3))^2 + (eos(2)-eos(3))^2)"

This way, the sequence produces close-to-mfe foldings with the targets (left)
and the targets are close together in terms of energy. (1 * ) scales the two
terms according to user choice.

### binary, combining:

+ - * /  :: the four basic operations
^        :: (^) generalized power function

### binary, apply function to many targets:

sum max min   :: run function over set of targets: sum(eos,1,2) or sum(eos,all)

### unary, apply to single target:

eos      :: energy of a structure: eos(1)
ed       :: ensemble defect of a structure: ed(3)

### nullary, constant for the current sequence:

Ged      :: global, weighted ensemble defect: Ged
gibbs    :: gibbs free energy of sequence
mfe      :: minimum free energy of sequence

### special:

logMN    :: requires four parameters logMN(0.2,0.3,0.3,0.2) penalizes according to given mono-nucleotide distribution in order of ACGU