The scripts and input files that accompany this demo can be found in the
demos/public directory of the Rosetta weekly releases.
KEYWORDS: LIGANDS DOCKING
Written by Kevin Drew (Bonneau Lab), kdrew at nyu dot edu
This demo shows how to run the hbs_design application. A hydrogen bond surrogate (HBS) is a helical mimetic scaffold used for inhibiting protein interactions. The demo shows the design of an hbs inhibitor for the MDM2-P53 protein interaction.
$> <path/to/Rosetta/>main/source/bin/hbs_design.default.linuxgccrelease @inputs/flags
./input/flags: User specified options.
./input/mdm2_hbs.pdb: Input structure where target is chain 1 and hbs is chain 2
-hbs_design_positions: Residues on hbs to design (numbering is relative to hbs, for example 3 is the third residue on hbs), default repacks with no design.
-pert_num: Number of pertubations during pertubation phase, default 10, production 100.
-design_loop_num: Number of pertubation + design cycles, default 10, production 10.
-nstruct: For production runs, use 1000.
Similar to other multi chain design protocols, the ddG is computed and is a good indicator of a good design. First sort by total score, take top 5 percent and then sort by REPACK_ENERGY_DIFF (ddG).
This app is inflexible to adjusting Monte Carlo temperatures, score functions, degree of rigid body pertubations, designing noncanonical amino acids, etc. The app also requires the hbs is close to a plausible binding mode with respect to the target.