This application in Rosetta3 was created and documented by David Johnson, et al.
This application is intended to automate the pocket optimization process, which previously had been done in two parts. Relax is performed and then the Pocket constraint is turned off an a full atom minimization is performed. If the pocket constraint is not used, it performs a simple relax and minimization, which is used to generate the unconstrained decoy comparison set.
Johnson DK and Karanicolas J. Druggable protein interaction sites are more predisposed to surface pocket formation than the rest of the protein surface. PLoS Comput Biol. 2013;9(3):e1002951 Johnson DK and Karanicolas J. Selectivity by small-molecule inhibitors of protein interactions can be driven by protein surface fluctuations. PLoS Comput Biol. 2015;11(2):e1004081
Sample command
pocket_relax.linuxgccrelease -database ~/Rosetta/main/database -in:file:s input.pdb -pocket_max_size 300 -pocket_num_angles 2 -score:patch pocket.wts.patch -cst_fa_file constraints -nstruct 1000 -pocket_zero_derivativesmake-exemplar options
General Rosetta Options
-database Path to rosetta databases
-in:file:s Input pdb file(s)
See [[Relax | application_documentation/relax]] documentation for other options
Pocket Constraint Options
-score:patch The PocketConstraint needs to be turned on
-cst_fa_file The PocketConstraint target residue and weight is specified here
-pocket_zero_derivatives The PocketConstraint has no derivitive, and this flag specifies to return derivitives of 0 during minimization phases of Relax
Pocket Identification Options
-pocket_num_angles Number of different pose angles to measure pocket score at, default is 1, but 2 is recommended to reduce grid and orientation artifacts
-pocket_grid_size Defines the dimensions of the PocketGrid centered on the target residue(s), or 10 Angstroms by default
-pocket_psp Mark Pocket-Solvent-Pocket events as well, default=false
-pocket_sps Unmark Solvent-Pocket-Solvent events, default=true
-pocket_surface_dist Distance to consider pocket point being "surface" and excluded from "deep volume"
-pocket_max_spacing Maximum residue-residue distance to be considered a pocket, default is 12 Angstroms
-pocket_min_size Minimum pocket size to score, in cubic Angstroms, default is 10 cubic Angstroms
-pocket_max_size Maximum pocket size to report, in cubic Angstroms, 0 for no limit (default)
-pocket_probe_radius Radius of surface probe molecule, default 1.0 Angstroms
-pocket_side Include only side chain residues for target surface, default=false
-pocket_filter_by_exemplar Additional filter generates an exemplar and then restricts the pocket to that exemplars, defaul=false
-pocket_ignore_buried Ignore pockets that are not solvent exposed, default=true
-pocket_only_buried Identify only pockets buried in the protein core (automatically sets -pocket_ignored_buried false), default=false
-pocket_static_grid By default the PocketGrid expands if pocket points are identified near the edge, this flag disables the autoexpanding feature.
-pocket_grid_spacing Defines the spacing of the PocketGrid, 0.5 by defaultpocket.wts.patch file
pocket_constraint = 1.0constraints file format
Pocket 0.25 97:A,143:A