Ligand File I/O

Before you can dock a ligand, you will need atom types and charges for every atom in the ligand. Currently, DOCK only reads the Tripos MOL2 format. For a single ligand (or several ligands), you can use Chimera in combination with antechamber to prepare a MOL2 file for the ligand (see Structure Preparation Tutorial) or various other visualization packages. During the docking procedure, ligands are read in from a single MOL2 or multi-MOL2 file. Atom and bond types are assigned using the DOCK 4 atom/bond typing parameter files.

There are several ligand output options, which write molecules to files whose names are formed using the output_file_prefix parameter. DOCK will always write out a scored molecules output file, which contains the best scoring pose for each molecule in the database. This will create a file called outputprefix_scored.mol2. Beyond this option, there are several other levels of sampling output:

• (1) Users can choose to write out orientations. This will create a file called outputprefix_orients.mol2. This will write out the molecules after they have been rigidly oriented and optimized. If anchor & grow is being used, this option will write out only the anchor fragment. All orientations generated will be written out, so be careful that the output does not get too huge.

• (2) Users can also write out conformers prior to final optimization. This will create a file called outputprefix_confs.mol2. Again, be aware that the number of molecules in the output file will be equal to the database size * the # of anchors per molecule * the number of orientations per anchor * the number of conformers per cycle. This file can grow quite large, so only use it on single poses or small databases.

• (3) Finally, users can write molecules ranked by score. This will create a file called outputprefix_ranked.mol2, which writes out the top N molecules from the database. This option disables the scored molecule output file by default, though users can override this and write out the best pose for each molecule as well.

NOTE: The following parameter definitions will use the format below:

       parameter_name [default] (value):
       #description

In some cases, parameters are only needed (questions will only be asked) if the parameter above is enforced. These parameters are indicated below by additional indentation.

Molecule Library Parameters

       * ligand_atom_file [database.mol2] (string):
         # The ligand input filename
       * ligand_outfile_prefix [output] (string):
         #The prefix that all output files will use
       * limit_max_ligands [no] (yes, no):
         #Limit the number of ligands to be read in from a library
             o max_ligands[1000]:
               #maximum number of ligands that will be read in from a library
       * read_mol_solvation [no] (yes, no):
         #Flag to read atomic desolvation information from ligand file
       * write_orientations [no] (yes, no):
         #Flag to write all anchor orientations
       * write_conformations [no] (yes, no):
         #Flag to write all fully grown conformations
       * skip_molecule [no] (yes, no):
         #Skip some number of molecules at the beginning of a library
             o initial_skip [0] (int):
               # The number of molecules to skip over at the beginning of a library
       * calculate_rmsd [no] (yes, no):
         #Flag to perform an RMSD calculation between the final molecule pose and its initial #structure.
             o use_rmsd_reference_mol [no] (yes, no):
               #Specify alternative geometric location for reference structure for RMSD
               #calculation
             o rmsd_reference_filename [ligand_rmsd.mol2] (string):
               #File containing alternative geometric location for reference structure for
               #RMSD calculation
       * rank_ligands [no] (yes, no):
         #Flag to enable a ligand top-score list. These ligands will be written to
         #outfile_ranked.mol2, and outfile_scored.mol2 will be empty by default
             o max_ranked_ligands [500] (int):
               #The number of ligands to be stored in the top score list
             o scored_conformer_output_override [no] (yes, no):
               #This flag causes all ligands to also be written to outfile_scored.mol2
       * number_scored_conformers_written [1] (int):
         #The number of scored poses for each ligand printed to output_scored.mol2
             o (if number_scored_conformers_written > 1):
               cluster_conformations [yes] (yes, no):
               #Flag to enable clustering of fully minimized conformations
             o cluster_rmsd_threshold [2.0] (float):
               #The cutoff to determine whether conformations should be
               #included in a particular cluster