Docking with constraints

KEYWORDS: DOCKING INTERFACES

In this demo, a peptide (chain B) is docked onto a protein (chain A) with user-defined constraints. The purpose of this demo is to illustrate the use of constraint files and as many different types of constraints as possible. The input files are based on PDB ID (2o2m) which is a "Crystal Structure Of Human Gαi1 Bound To The Goloco Motif Of Rgs14". The protein is chain A. The peptide is chain B.

Protocol

A general overview of the protocol is available at:
http://www.rosettacommons.org/manuals/archive/rosetta3.2.1_user_guide/app_docking.html

A write-up of the file format for Constraints is available at:
http://www.rosettacommons.org/manuals/archive/rosetta3.2.1_user_guide/constraint_file.html

High level overview:

1. Docking Prepack

   • Useful to optimize all of the sidechains on both partners
   • http://graylab.jhu.edu/Rosetta.Developer.Documentation/all_else/de/d69/docking_prepack_protocol.html

2. Docking with constraints. In general, constraints are typically defined for CA atoms of the partner sidechains.

   • Docking will honor AtomPairContraint, AmbiguousConstraint, SiteContraint. For additional information on contraints, see "Constraints" section below.

3. Analysis

   • The expected output of the docking run is (1) a decoy with both docked partners and (2) a score file with score breakdown for each decoy
   • Typical analysis would be to sort the generated score file with a command line i.e. 'sort -nk 28` where the integer identifies the column number for the quality to sort on.

Constraints

A good overview of constraints is available in the documentation:
http://www.rosettacommons.org/manuals/archive/rosetta3.2.1_user_guide/constraint_file.html

The three constraints which are honored by the Docking Protocol are:

• AtomPairConstraint
• AmbiguousConstraint
• SiteConstraint.

AtomPair and AmbiguousConstraint are described the above documentation for Rosetta 3.2.1. A SiteConstraint allows you to specify that a particular residue should be in contact with a particular chain. An example of a SiteConstraint is:

SiteConstraint CA 4A D FLAT_HARMONIC 0 1 5

This will add a FLAT_HARMONIC potential with the parameters 0 1 5 (recommended) around the distance between the CA of residue 4 (PDB numbering) on chain A and the closest CA on chain D to the ScoreFunction.

To run these examples, use

$> <path/to/Rosetta/main/source/bin/>/docking_protocol.default.linuxgccrelease @rosetta_inputs/options
$> <path/to/Rosetta/main/source/bin/>/docking_protocol.default.linuxgccrelease @rosetta_inputs/options.constraint_ambiguous
$> <path/to/Rosetta/main/source/bin/>/docking_protocol.default.linuxgccrelease @rosetta_inputs/options_wo_constraints