Ligand File Input

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Ligand File Input

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.

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
  • limit_max_ligands [no] (yes, no): #Limit the number of ligands to be read in from a library
    • max_ligands[1000]: #maximum number of ligands that will be read in from a library
  • skip_molecule [no] (yes, no): #Skip some number of molecules at the beginning of a library
    • initial_skip [0] (int):> # The number of molecules to skip over at the beginning of a library
  • read_mol_solvation [no] (yes, no): #Flag to read atomic desolvation information from ligand file
  • calculate_rmsd [no] (yes, no): #Flag to calculate the heavy atom RMSD between the final ligand pose
    #and its initial structure.

Ligand RMSD

Three types of root mean square distance (RMSD) values are reported when "calculate_rmsd = yes". These values can be found in the header of the output MOL2 file.

(1) Standard heavy-atom RMSD (HA_RMSDs): This is the standard pair-wise RMSD calculation between the non-hydrogen atoms of a reference conformation a and a pose conformation b for a ligand with N total heavy atoms of index i:

If the HA_RMSDs is "-1000.0", then there is an inconsistency in the number of heavy atoms between the reference and the docked conformer.

(2) Minimum-distance heavy-atom RMSD (HA_RMSDm): This measure is based on the RMSD implementation used in Autodock Vina (Trott and Olson, J. Comput. Chem. 2010), which does not explicitly enforce one-to-one mapping. Rather, atom pairings between reference conformation a and pose conformation b are determined by the minimum distance to any atom of the same element type, and it may be an under-prediction of the true RMSD.

(3) Hungarian (symmetry-corrected) heavy-atom RMSD (HA_RMSDh): The final RMSD implementation is based on an O(N^4) implementation of the Hungarian algorithm (Kuhn, Nav. Res. Logist. Q. 1955; Munkres, J. Soc. Indust. Appl. Math. 1957). The algorithm solves the optimal assignment between a set of reference ligand atoms a and a set of pose ligand atoms b of the same size. For all groups of atoms of the same Sybyl atom type, a cost matrix M is populated where each matrix element mij is equal to the distance-squared between reference atom ai and pose atom bj. The Hungarian algorithm is used to determine one-to-one assignments between reference and pose ligand atoms such that the total distance between atoms is minimized. The new assignments c(i) are fed into the standard RMSD function in order to compute a symmetry-corrected RMSD. If the HA_RMSDh is "-1000.0", then there is an inconsistency in the number of atoms of at least one atom type between the reference and the docked conformer.

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