RosettaDock Applications

The scientific component of docking protocol is the same as the original RosettaDock. The docking protocol is still based on the RosettaDock algorithms. RosettaDock works by simultaneous optimization of side-chain conformation and rigid body position of the two docking partners. The former is performed by a packing algorithm, and the latter is performed by a rigid-body Monte Carlo Minimization (MCM) strategy. For more, on understanding RosettaDock see RosettaDock tutorials: http://graylab.jhu.edu/~mdaily/tutorial/basics_main.html

Dock Applications

We have one dock application ready at mini/src/apps/public/docking The name of the applications is docking_protocol. You can find the executable of this application in mini/bin/ after successfully compiling. With this application you can do all major rigid-body docking functions from Rosetta++, including global docking, local perturbations, and high-resolution refinement of complex structures.

Input Files

RosettaDock application's input file is a PDB file which holds two docking partners.The two independently movable protein units in Rosetta. For a complex of two polypeptide chains, a docking partner has the same meaning as a polypeptide chain. For three or more chains (e.g. in an antibody-antigen run), a docking partner contains multiple chains. Each partner is ended by a "TER" mark in the pdb file.

Command Lines and Options

1. Sample Command:

   docking_protocol.linuxgccrelease @flags > docking,log& 

2. Options used in RosettaDock.

   *Input Options:
   --------------
   -in:database                  Path to Rosetta databases. [PathVector]
   -in:file:s                    Input file path.[FileVector]
   -nstruct                      Number of output structures per use. [Interger]
   
   *Docking Options:
   -----------------
   -docking:dock_pert            Initial perturbation: Do a small perturbation with partner two. Followed by DEGREES and ANGSTROMS. Standard values for a local
                                 perturbation are 3D and 8A.[RealVector] For Example: -docking:dock_pert <degrees> <angstroms>
   -docking:spin                 Initial perturbation: Spin a second docking partner around axes from center of mass of partner 1 to partner 2. [Boolean]
   -docking:randomize1           Initial perturbation: Randomize the first docking partner. [Boolean]
   -docking:randomize2           Initial perturbation: Randomize the second docking partner. [Boolean]
   -docking:docking_local_refine Initial perturbation: skips initial perturbation and centroid mode search and goes direct to fullatom mode.[Boolean]
   -ex1 -ex2_aro                 Standard side chain flags for using expanded rotamer libraries during packing for fullatom docking. [Boolean]
   -docking:dock_ppk             Fullatom mode: prepacking Pack all side chains of component proteins to lowest energy conformation. [Boolean]
   -docking:dock_mcm             Fullatom mode: Monte Carlo minimization (MCM). Do a MC minimization search. [Boolean]
   -docking:dock_min             Fullatom mode: energy minimization. Does a rigid-body energy minimization instead of MCM. [Boolean]
   
   *Output Options:
   -----------------
   -out:file:fullatom            Enable full-atom output of pdb.[Boolean]
   -out:file:o                   Name of the output score file.[String]
   

Result Interpretation

There are two kinds of output files generated during a docking run. One is pdb file, the other is energy fasc (fullatom scoring) file.

total_score:                  Final Score.
rms:                          Rmsd of the decoy to the native.
cen_rms:                      RMSD of the decoy following centroid mode, to the native.
dslf_ca_dih:                  ca dihedral score in current disulfide
dslf_cs_ang:                  csangles score in current disulfide
dslf_ss_dih:                  dihedral score in current disulfide
dslf_ss_dst:                  distance score in current disulfide
fa_atr:                       lennard-jones attractive.
fa_dun:                       internal energy of sidechain rotamers as derived from Dunbrack's statistics.
fa_rep:                       lennard-jones repulsive.
fa_sol:                       lazaridis-karplus solvation energy.
hack_elec:
hbond_bb_sc:                  sidechain-backbone hydrogen bond energy
hbond_lr_bb:                  backbone-backbone hbonds distant in primary sequence
hbond_sc:                     sidechain-sidechain hydrogen bond energy
hbond_sr_bb:                  backbone-backbone hbonds close in primary sequence
interchain_env:               interface environmental effects
interchain_pair:              pairwise interactions
interchain_vdw:               Van der Waals
ref:                          reference energy for each amino acid
st_rmsd:                      RMSD of the decoy following the initial perturbation, to the native
description:                  input pdb tags

References

Gray, J. J.; Moughon, S.; Wang, C.; Schueler-Furman, O.; Kuhlman, B.; Rohl, C. A.; Baker, D., Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. Journal of Molecular Biology 2003, 331, (1), 281-299. Gray, J. J.; Moughon, S. E.; Kortemme, T.; Schueler-Furman, O.; Misura, K. M.; Morozov, A. V.; Baker, D., Protein-protein docking predictions for the CAPRI experiment. Proteins 2003, 52, (1), 118-22. Wang, C., Schueler-Furman, O., Baker, D. (2005). Improved side-chain modeling for protein-protein docking Protein Sci 14, 1328-1339. Schueler-Furman, O.; Wang, C.; Baker, D., Progress in protein-protein docking: atomic resolution predictions in the CAPRI experiment using RosettaDock with an improved treatment of side-chain flexibility. Proteins 2005, 60, (2), 187-94. Wang, C., Bradley, P. and Baker, D. (2007) Protein-protein docking with backbone flexibility. Journal of Molecular Biology, in press, DOI, http://dx.doi.org/10.1016/j.jmb.2007.07.05 [update!]

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