RNA Design Application

-------------------------- This application carries out combinatorial optimization of nucleobase type and conformation along with 2'-OH torsions, in the context of a pre-specified RNA backbone. It is very similar to the Rosetta fixed-backbone protein design algorithm, and has been used to test the new Rosetta RNA potential. Unfortunately, it is not presently very optimized; the precalculation of rotamer energies takes a while. Runs on RNA backbones longer than ~ten nucleotides take many minutes or hours; algorithm improvements implemented in future releases will greatly speed this up. Test command line:

rna_design.macosgccrelease -s chunk001_uucg_RNA.pdb   -nstruct 3  -ex1:level 4 -dump -score:weights rna_hires.wts

[ The test pdb can be found at mini/test/integration/tests/rna_design/. ]

Applications

We have one RNA denovo application: rna_design.cc. You can find the executable of the applications in mini/bin after successfully compiling.

Input Files

Pdb file with desired backbone.

command Command lines and Options: In the new release, user can simply use a flag file to instead of enter bunch of flags everytime.flag file is a plain txt file which holds a list of options

• Sample command: rna_design.linuxgccrelease > rna_design.log
• Options in flag file for RNA DESIGN applications:

  -database                                        Path to rosetta3 databases. [PathVector]
  -in:file:s                                       Name(s) of single PDB file(s) to process. [FileVector]
  -nstruct                                         Number of times to process each input PDB. [Integer]
  -ex1:level <n>                                   Use extra chi1 sub-rotamers for all residues that pass
                                                   the extrachi_cutoff.
                                                   [Boolean]
                                                   The integers that follow the ex flags specify the pattern
                                                   for chi dihedral angle sampling.
                                                   There are currently 8 options; they all include the original
                                                   chi dihedral angle No. 4 means: EX_TWO_HALF_STEP_STDDEVS
                                                   [-1,-1/2,0,1/2,1 standard deviations].
  -dump                                            Generate pdb output,default:false. [Boolean]
  -score:weights rna_hires.wts                     Name of weights file, default is standard. [String]
  

Result Interpretation

***Energy interpreter for fullatom silent output:
score                                            Final total score
fa_atr                                           lennard-jones attractive
fa_rep                                           lennard-jones repulsive
fa_intra_rep                                     Lennard-jones repulsive between atoms in the same residue
lk_nonpolar                                      lazaridis-karplus non-polar solvation energy
hack_elec_rna_phos_phos                          Simple electrostatic repulsion term between phosphates
hbond_sr_bb_sc                                   backbone-sidechain hbonds close in primary sequence
hbond_lr_bb_sc                                   backbone-sidechain hbonds distant in primary sequence
hbond_sc                                         sidechain-sidechain and sidechain-backbone hydrogen bond energy
ch_bond                                          Carbon hydrogen bonds
geom_sol                                         Geometric Solvation energy for polar atoms
rna_torsion                                      RNA torsional potential.
atom_pair_constraint                             Atom pair distance constraints score?
angle_constraint                                 (not in use)
rms                                              rmsd

***If you use the sample flag files, there are also other output files generated.
start.pdb:                                       Idealized structure
S_000*.pdb:                                      Output of the rna denovo design.
chunk001_uucg_RNA.sequence_recovery.txt:         This is a simple report for design identity of each RNA residue and structure.

References

Das, R., Karanicolas, J., and Baker, D. (2008), "A high resolution force field for predicting and designing RNA noncanonical structure", submitted.

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