Guided Ligand Replacement

Overview

Input files

Output files

References

List of all guided_ligand_replacement keywords

Overview

The Guided Ligand Replacement (GLR) tool is designed to use prior knowledge from a previously fit ligand to expedite the fitting of a "similar" ligand into the same or "similar" protein. The similarity required between the pair of ligands can be as little as a few atoms.

The proteins are overlayed using phenix.superpose_pdbs. The ligands are matched using the electronic Ligand Builder and Optimization Workbench (eLBOW) via another tool called phenix.superpose_ligands. Once the ligand has been fit, a Real-Space Refinement (RSR) is performed and the final model written to disk.

Input files

GLR requires a number of inputs and also has some options, all of which are provided using the phil formalism. The list of required inputs:

• guide_pdb_file_name: this is a PDB file containing a model-ligand model.
• protein_pdb_file_name: this is a file containing the protein model of current interest into which the ligand is to be fit.
• map_coeffs_file_name: this is a maps coefficients file output from a phenix.refine run.

The input for the ligand can be any input file that is readable by eLBOW. Either or both of the following phil parameters can be used.

• ligand_input_file_name: this is a file containing chemical information about the ligand.
• ligand_cif_file_name: this is the of a ligand restraints file for the RSR step. If not supplied, the restraints are generated from ligand_input_file_name.

Optional inputs include:

• ligand_selection_in_guide_model: this selects a ligand in the guiding model. While GLR tries to make a sensible selection based on ligand code or uniqueness, it may be necessary to make an explicit selection.
• phenix.superpose_pdbs: this allows selection of the same parameters as in the standalone program.

Output files

By default, GLR will generate a PDB file with the fit ligand.

References

• Moriarty NW, Grosse-Kunstleve RW, Adams PD. electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation. Acta Cryst. 2009, D65:1074-1080.

List of all guided_ligand_replacement keywords

------------------------------------------------------------------------------- 
Legend: black bold - scope names
        black - parameter names
        red - parameter values
        blue - parameter help
        blue bold - scope help
        Parameter values:
          * means selected parameter (where multiple choices are available)
          False is No
          True is Yes
          None means not provided, not predefined, or left up to the program
          "%3d" is a Python style formatting descriptor
------------------------------------------------------------------------------- 
guided_ligand_replacement
   input
      guide_pdb_file_name= None PDB filename containing protein model and fit
                           ligand
      protein_pdb_file_name= None PDB file containing protein but not a ligand
      ligand_input_file_name= None File contains chemical input of a ligand
      data_file_name= None Amplitudes or intensities
      map_coeffs_file_name= None Map coefficients from a refinement of the apo
                            model
      ligand_cif_file_name= None This restraints file will be used for the
                            real space refinement. If not suplied, a set of
                            restraints are generated from the ligand input.
      ligand_selection_in_guide_model= None The specific ligand to use from
                                       the guide structure
      real_space_refinement= lockit *ideal off
      real_space_refinement_selection_radius= 5.
   output
      file_name= None Defaults to current directory
      job_title= None Job title in PHENIX GUI, not used on command line
   superpose_pdbs
      input
         pdb_file_name_protein= None Name of PDB file with model to fit to
         pdb_file_name_guide= None Name of PDB file with model that will be
                              fit to pdb_file_name_protein
      alignment Set of parameters for sequence alignment. Defaults are good
                for most of cases
         alignment_style= local *global
         gap_opening_penalty= 1
         gap_extension_penalty= 1
         similarity_matrix= blosum50 dayhoff *identity
      validation
         rmsd_cutoff= 2.
         similarity_cutoff= 80.
   superpose_ligands
      quick= True
   lockit_parameters
      lbfgs_max_iterations= 500
      finishing_geometry_minimization
         cycles_max= 100
         first_weight_scale= 0.1
         cycle_weight_multiplier= 1.0
         superpose_cycle_end_with_cycle_start= False
         dihedral_restraints= False
         output_file= Auto
      real_space_target_weights
         first_sample= 10
         sampling_step= 30
         number_of_samples= 10
         bond_rmsd_target= 0.03
         worst_acceptable_bond_rmsd
            pool_size= 10
            max_pool_average= 0.1