glideEM.py Command Help
Command: $SCHRODINGER/run -FROM psp glideEM.py
usage: $SCHRODINGER/run -FROM psp glideEM.py <struct_file> -map <map_file> -ligand_asl <ASL>|-ligand_struct <ligand_struct_file>|-ligand_smiles <SMILES> [options]
Place ligands using a combination of the protein contacts and the experimental density
Input structure and experimental map should be given along with ligand and in some cases binding site information. Input structure should contain receptor structure. If the ligand structure is part of the input structure ligand ASL should be given to specify the ligand to be docked. Otherwise, either prepped ligand structure should be given as a separate file or ligand SMILES should be provided. In the case of SMILES, binding site also should be specified to define where to dock and LigPrep will run for preparing 3D ligand structure with appropriate ionization and tautomeric states. Binding site should also be determined with Docking Site Options for the former two ligand options (ASL and ligand_struct_file) if the ligand is not already in the binding site. See the examples to choose your parameters suitable for your input.
As a first step of the program, docking grid is formed based on the docking center and the ligand size using Glide. Then, local density is calculated from experimental density map based on the grid center and the ligand size. Finally, the ligand is placed in the docking center and five poses are outputted per ligand by default using Glide.
Phenix/OPLS structure refinement can be run subsequently after Glide docking if corresponding options are supplied. Output structures are sorted based on Glide docking score by default, or Ligand Cross Correlation if Phenix/OPLS is included.
options:
-h, --help show this help message and exit
-v show program's version number and exit
Input options:
struct_file Starting Structure with the receptor and ligand fully
prepped, and hydrogens present on both the protein and
ligand. If the ligand is not included, provide a
ligand struct file or ligand SMILES.
-map MAP Experimental data file used during workflow. Supported
extensions include .ccp4, .mrc, and .map for cryo-EM,
and .cif and .mtz for X-ray data. If .cif or .mtz, the
structure factors will be automatically converted to a
2Fo-Fc density map with sf2map.py
-ligand_asl LIGAND_ASL
ASL pattern corresponding to the ligand to be
redocked, matching the ligand atoms in the given
struct_file. This should typically be a small
molecule, for linear peptides use '-mode peptide'.
-ligand_struct LIGAND_STRUCT
Prepped ligand structure to use in docking if it is
not already included in the struct_file.
-ligand_smiles LIGAND_SMILES
Ligand SMILES representation for docking if the ligand
is not already present in the receptor complex or is
in a separate ligand structure file.
Docking Site Options:
-binding_site_asl BINDING_SITE_ASL
ASL pattern corresponding to the binding site where
the ligand will be docked. This should typically be
one or several binding site residues. If specified,
the ligand is moved to the binding site defined by the
provided ASL.
-docking_site_xyz X Y Z
Set center of docking grid by providing Cartesian
coordinates as a sequence (e.g. 10.0 5.0 7.5).
Job Control Options:
-jobname JOBNAME, -JOBNAME JOBNAME, -j JOBNAME
Set the base name of outputs
-cpu_subhost CPU_SUBHOST
Subhost for CPU jobs
-n_cpu N_CPU Number of CPUs to use
-OPLSDIR OPLSDIR Specifies directory for custom forcefield parameters
General Options:
-nposes NPOSES Number of poses to return; default = 5
-mode {quick,normal,exhaustive,refine,peptide,macrocycle}
Extent of sampling to run for each ligand. All modes
affect the conformer sampling in Glide. 'peptide' mode
additionally pre-samples conformers of linear peptides
with ConfgenX; default = 'exhaustive'
-ligand_conformations_file LIGAND_CONFORMATIONS_FILE
Optional ligand conformations file to use during
docking.
-remove_water Removes waters during docking and adds them back if
they do not clash with the docked ligand.
-grid_only Stops the program after creating a docking grid
-receptor_cutoff RECEPTOR_CUTOFF
For large systems, only residues within a given cutoff
of the ligand can be considered. This should typically
be set to a value significantly larger than the box
size, which can be up to 50 A based on the size of the
ligands
Force Field Builder Options:
-run_ffbuilder Creates a customized force field for the torsions
present in the ligand. If an OPLS_DIR is specified and
torsions are missing from the directory, OPLS_DIR will
be modified to include the missing parameters.
Peptide Mode Options:
-nconformers NCONFORMERS
Maximum number of conformers to save when presampling
the ligand. Only used in 'peptide' mode; default = 50
Glide Options:
-gridgen_option GRIDGEN_OPTIONS
Glide options to pass through to the grid generation
step. These should be in the form <keyword>=<value>.
-docking_option DOCKING_OPTIONS
Glide options to pass through to the docking step.
These should be in the form <keyword>=<value>.
-docking_cons_file DOCKING_CONS_FILE
Constraints to pass through to the Glide docking run.
Phenix Refine Options:
-phenix_opls_refine {none,only_ligands,full}
Refine with Phenix/OPLS. This requires an installed
version of Phenix (1.16+) and the PHENIX environment
variable to be set. This also requires the resolution
to be provided. Choices: 'none' (default): No
refinement performed with Phenix/OPLS 'only_ligands':
Apply refinement to the whole system but only use OPLS
forcefield for the ligands 'full': Apply refinement
with OPLS for the whole system
-phenix_refine_option PHENIX_REFINE_OPTIONS
Supply additional parameters for Phenix/OPLS backend.
Should be in the form <key>=<value>. If multiple
options need to be set, this command can be repeated
multiple times. i.e. -phenix_refine_option weight=1
-phenix_refine_option run="minimization_global+local_g
rid_search+morphing+simulated_annealing+adp"
-phenix_refine_params_fn PHENIX_REFINE_PARAMS_FN
Supply additional parameters for the Phenix/OPLS
backend using a phenix.refine or
phenix.real_space_refine parameter file.
Jaguar Ligand Pose Energy Options:
-calc_jaguar_pose_energy
Calculate the Ligand Pose Energy with Jaguar.
-jaguar_option JAGUAR_OPTIONS
Jaguar options to pass through to the pose energy
step. These should be in the form <keyword>=<value>.
-jaguar_restraint_strength JAGUAR_RESTRAINT_STRENGTH
Restraint strength in kcals/mol/Degree to restrain
torsions to during QM pose energy calculations;
default = 1.0
-jaguar_restraint_width JAGUAR_RESTRAINT_WIDTH
Flat bottom width of restraint in degrees to restrain
torsions during QM pose energy calculations; default =
30.0
MMGBSA Protein Ligand Energy Options:
-calc_mmgbsa_energy Calculate the MMGBSA energy between the protein and
ligand for each pose.
-mmgbsa_option MMGBSA_OPTIONS
MMGBSA options to pass through to the pose energy
step. These should be in the form <keyword>=<value>.
Options for Outputting a Local Region of the System:
-write_local_region Write an additional output file containing only the
atoms near the ligand.
-write_region_distance_cutoff WRITE_REGION_DISTANCE_CUTOFF
Distance around the ligand to write in Angstrom;
default = 30
-write_region_min_molecule_size WRITE_REGION_MIN_MOLECULE_SIZE
Minimum size of molecules to keep after deleting atoms
beyond a cutoff from the ligand; default = 50
-save_local_map Save a normalized local map around the ligand. This is
the map that the ligand will be docked into, so it can
be useful for debugging purposes.
GlideEM/Phenix Specific Options:
-resolution RESOLUTION
Supply a resolution of the map. This will only be used
for optional Phenix/OPLS refinement
Job Control Options:
-HOST <hostname> Run job remotely on the indicated host entry.
-WAIT Do not return a prompt until the job completes.
-D, -DEBUG Show details of Job Control operation.
-NOJOBID Run the job directly, without Job Control layer.
Standard Options:
-NOLAUNCH Set up subjob inputs, but don't run the jobs.
Examples:
Docking by providing the ligand ASL where the ligand is part of the input structure:
$SCHRODINGER/run -FROM psp glideEM.py 6dwz.mae -map 6dwz.mrc -ligand_asl "chain A AND res.ptype 8PR"
Docking by providing the ligand structure placed in the binding site separately:
$SCHRODINGER/run -FROM psp glideEM.py 6dwz_nolig.mae -map 6dwz.mrc -ligand_struct 8PR.mae
Docking into site defined by binding site ASL if ligand is not already in the site:
$SCHRODINGER/run -FROM psp glideEM.py 6dwz_nolig.mae -map 6dwz.mrc
-ligand_struct 8PR_displaced.mae -binding_site_asl "Chain A AND res.n 95 172 176 341"
Dock ligand into the binding site given by a Cartesian coordinate:
$SCHRODINGER/run -FROM psp glideEM.py 6dwz_nolig.mae -map 6dwz.mrc
-ligand_struct 8PR_displaced.mae -docking_site_xyz 0 10 20
Docking a ligand generated from given SMILES string:
(This also requires specifying the binding site. LigPrep will run for the ligand.)
$SCHRODINGER/run -FROM psp glideEM.py 6dwz_nolig.mae -map 6dwz.mrc -ligand_smiles
Fc1ccc(cc1)[C@@H]2CCNC[C@H]2COc3ccc4OCOc4c3 -binding_site_asl "Chain A AND res.n 95 172 176 341"
Docking by providing ligand conformations:
$SCHRODINGER/run -FROM psp glideEM.py 6dwz.mae -map 6dwz.mrc -ligand_asl "chain A AND res.ptype 8PR"
-ligand_conformations_file 8PR_conformers.mae
Presample 20 linear ligand/peptide conformations with confgenx and dock each:
$SCHRODINGER/run -FROM psp glideEM.py 6ddf.mae -map 6ddf.mrc
-ligand_asl "Chain D AND res.n 1-5" -mode peptide -nconformers 20
Dock ligand and run Phenix/OPLS refinement on each output pose:
$SCHRODINGER/run -FROM psp glideEM.py 6dwz.mae -map 6dwz.mrc -ligand_asl "chain A AND res.ptype 8PR"
-phenix_opls_refine full -resolution 4.3