Global Matching Sphere Optimization
Goal
To optimize your matching sphere (MS) setups getting more enrichment with fewer spheres.
Description
The program performs optimization of matching spheres using genetic algorithm. It selects spheres from two sets:
- heavy atoms of xtal-lig
- spheres prepared by SPHGEN program
At each generation, N matching sphere sets are created, containing a maximum of M spheres each. Then retrospective docking is done for each set, and sets are ranked by the enrichment, RMSD of the docked pose to the experimental one. After that, a quarter of sets "survive" and produce a new generation by direct transfer, mutations, and crossover. This process is repeated until enrichment, RMSD and minimum number of spheres do not change substantially in 10 generations.
The program consists of two main modules:
- a Python script (
juggler.py) that performs MS generation, optimization, and ranking. - a Bash script, that watches created directory structure, runs docking and processes docking results
Setup
So far, the program is running on Wynton. LMK if you are interested in launching it on Gimel or other clusters.
Prepare dockfiles directory with any tools of your liking (blastermaster, dockopt etc). You will also need rec.pdb, rec.crg.pdb, xtal-lig.pdb, ligands.names, decoys.names and a sdi directory with the paths to ligand .tgz files. To get RMSD of xtal-lig docked poses to the experimental pose, your xtal-lig.pdb must have correct bond orders and atom valences. You can edit it in Schrodinger and save as xtal-lig.pdb.
Prepare juggler_config.yml file. Put it into an empty directory.
Enter a screen environment so your run is not interrupted if you disconnect your SSH session. Then do:
source /wynton/group/bks/soft/python_envs/python3.8.5.sh
python /wynton/home/irwin/ak87/ak87/UCSF/NEOCORTEX/SCRIPTS/RELEASE/juggler.py
You can detach from the screen (Ctrl-A d).
Open a new screen. In the same directory launch a docking daemon
/wynton/home/irwin/ak87/ak87/UCSF/NEOCORTEX/SCRIPTS/RELEASE/rundockd-wynton-taskid.sh
You can run other calculations on Wynton in the meantime, as Juggler will track the task IDs that it launched.