Optimise the atomistic charges or van der Waals parameters of a ligand to maximize receptor binding affinity.
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via conda:
conda config --add channels omnia --add channels conda-forge
conda install -c adw62 ligcharopt
[--job_type=STRING] FEP jobs that can be performed,
default: 'F'
options:
F - Fluorine
Cl - Chlorine
N - Nitrogen
S - Sulphur
[--output_folder=STRING] Directory for output,
default: './mol_name_job_type'
[--ligand_name=STRING] String ligand is adressed by in input mol2 file,
default: 'MOL'
[--mol_name=STRING] Name of input mol2 file containg ligand,
default: 'ligand'
[--complex_name=STRING] Name of input pdb file containg ligand,
default: 'complex'
[--solvent_name=STRING] Name of input pdb file containg ligand,
default: 'solvent'
[--yaml_path=STRING] Path to yaml file containg options for yank exsperiment builder,
default: './setup.yaml'
[--o_atom_list=LIST] List of indices of oxygen atoms in ligand.mol2 to be replaced with S,
default: None
[--c_atom_list=LIST] List of indices of carbon atoms in ligand.mol2 to be replaced with N,
default: None
[--h_atom_list=LIST] List of indices of hydrogen atoms in ligand.mol2 to be replaced with F or Cl
default: None
[--auto_select=STRING] Automatic selction of indicies for mutation based on input,
default: None
options:
1 - for O.1 oxygens, C.1 carbons or their associated H
2 - for O.2 oxygens, C.2 carbons or their associated H
3 - for O.3 oxygens, C.2 carbons or their associated H
ar - for O.ar oxygens, C.ar carbons or their associated H
[--num_frames=INT] Number of frames of trajectory to collect for objective, frames spaced by 5ps,
default: 500
[--net_charge=INT] Net charge of ligand to be passed to antechamber for paramterisation, net_charge should also be set in setup.yaml,
default: 0
[--gaff_ver=INT] Gaff version to use in paramterisation,
default: 2
options: 1, 2
[--equi=INT] Number of steps of equilibriation, each step is 2fs,
default: 100
[--num_fep=INT] Number of repeates to do when testing the set of optimised charges with full FEP,
default: 1
[--charge_only=BOOL] Boolean to determine if only charge parameters should be changed,
note: Should be True for optimisation
default: False
[--vdw_only=BOOL] Boolean to determine if only van der Waals parameters should be changed,
default: False
[--optimize=BOOL] Boolean to determine if an optimisation is being performed,
default: False
[--opt_name=STRING] Name of optimisation being performed,
default: scipy
options: scipy
[--rmsd=FLOAT] RMSD limit placed on the original and optimised charges,
default: 0.03 q_e
[--opt_steps=INT] Number of optimisation steps to perform,
default: None
[--central_diff=BOOL] Boolean to deterimine if the optmiser will calculate the gradient with a central of forward difference,
default: True
[--num_gpu=INT] Number of GPU for the node where the calculation is run,
note: This software is not configured to use MPI and should only be run on one node, however this node may have multiple GPUs
default: 1
[--exclude_dualtopo=BOOL] Excludes any atoms in daul topology from seeing each other.
note: Fluorines are added to a dual topology as typically the hydrogens they are mutated from are constrained. It is not possiable to alchemically interpolate the hydrogen constraint into a C-F harmonic bond.
default: 1
Optimise atomic charges of a ligand and verify the ddG of this optimisation with one full FEP calculation
LigCharOpt --optimize=1 --charge_only=1 --yaml_path='./setup.yaml'
Run a full FEP calculations on all mutants with 'O.3' oxygens swapped for S
LigCharOpt --job_type='S' --auto_select=3 --yaml_path='./setup.yaml'