Modeling structures of RNA-protein complexes

Metadata

Author: Kalli Kappel (kappel at stanford dot edu)
Last updated: April 2018

Application purpose

Model 3D structures of RNA-protein complexes using a fold-and-dock method.

Code and demo

Code is available through rna_denovo. A demo is available in demos/public/rnp_structure_prediction.

Required inputs

Complete structures of all proteins that are part of the RNA-protein complex you want to model. (If an experimental structure is not available, you can use other Rosetta protocols to build a model.)
A fasta file containing the full sequence of the RNA-protein complex that you’re modeling.
A secondary structure file for your RNA-protein complex. Secondary structure for the protein should be specified by dots. The secondary structure should be the same length as the sequence found in the fasta file.

Optional inputs

Additional PDB files specifying parts of the RNA structure, e.g. ideal A-form RNA helices. Note: if you want to enforce a specific rigid body orientation between your protein and an RNA structure, they must both be specified in the same PDB file!
A constraint file, which can be used to incorporate experimental data (such as specific contacts, distance restraints, etc.) into the modeling.
A density map: see the DRRAFTER pipeline for more information about building models into density maps.

Running the code

Models are built with the Rosetta fold-and-dock method for RNA-protein complexes, which combines FARNA RNA folding with RNA-protein docking. An example command line is below:

rna_denovo –f fasta.txt –secstruct_file secstruct.txt –s protein_structure.pdb –minimize_rna false –nstruct 100

Options for modeling RNA-protein complexes

-ramp_rnp_vdw: Gradually turn on rnp_vdw scoring during the run.
-convert_protein_CEN: Convert protein residues to centroid mode during low-res fragment assembly.
-rna_protein_docking: Do RNA-protein docking. This will be turned on by default if both RNA and protein residues are specified in the fasta file, and the rigid body orientation is not predetermined by one of the input structures.
-docking_move_size: A number between 0.0 and 1.0 that controls the magnitude of the rigid-body docking moves. 0.0 corresponds to the smallest docking moves and 1.0 to the biggest. Default is 1.0.
-rnp_high_res_relax: Do additional all-atom refinement for RNA-protein complexes (sidechain packing, small docking moves, single residue fragment insertions). Default: true.
-rnp_high_res_cycles: The number of all-atom refinement cycles to perform (above).
-rnp_pack_first: Pack protein sidechains first in all-atom refinement (above). Recommended: true.
-rnp_min_first: Minimize the RNA-protein structure (in the full-atom energy function) before doing any further high-resolution refinement (above). Recommended: true.
-FA_low_res_rnp_scoring: RNA-protein low-resolution scoring using full atom protein residues.