Covalent ligand with rigid receptor

Generating target file, detailed explanations

The agfr command is used to compute grids of affinity values for a given set of atom types. This calculation is performed using the AutoGrid4 software program. These affinity values are calculated on evenly spaced grid points for a 3D box (docking box) placed over the receptors site targeted for automated docking.

> agfr -r 3c9w.pdbqt

-b user 28.565 6.329 6.985 22.5 22.5 22.5

-c 1593 1596

-t 1591

-x A:CYS164

-o 3c9w_cov_cmdline

The receptor is specified using the r/--receptor command line option. This option is required.

The position and size of the box are specified manually. Note that padding does not apply in this case.

The PDB serial numbers (as they appear in the pdbqt file) of the 2 receptor atoms forming the covalent bond are specified using the c/--covalentBond option.

The third atom defining the covalent attachment is used to compute the torsion angle of the covalent bond. It is specified using the t/--covalentTorsionAtom option.

The x/--covalentResidues option allows to limit the traversal of the receptor to a list or residues. This is needed sometimes as covalent residues can create bonds with the receptor other than the covalent attachment and this is the case with the native ligand of 3cw9. When agfr identifies the sub-tree beyond the covalent bond to find which atoms to cut out of the receptor for calculating affinity maps, it would include a large part of the receptor because of the spurious bond the ligand makes with the receptor and cut out in excess of 1600 atoms. The x option prevents this from happening.

The agfr command generates a target file with a .trg extension. This file will be saved under the name specified by the o/--output command line option. When omitted, a unique and descriptive filename will be created automatically. The target file contains the calculated affinity maps, translational points for placing the ligand in sensible places in the docking box, and meta data about the gird size, position, spacing, receptor atoms involved, affinity maps, etc. These files can be inspected using the about command.

By default, maps are computed for all AutoDock4 atom types. The list of atom types for which to compute affinity maps can be set using the m/--mapTypes option.  Generating affinity maps for fewer atom types generates smaller target files and takes less time to perform the calculation, however, such a target file cannot be used for docking ligands containing atoms for which the target files does not contain the affinity map.

Running this command generates the following output (saved in 3c9w_cov_cmdline.log)

 

fiji:rib sanner$ agfr -r 3c9w.pdbqt -b user 28.565 6.329 6.985 22.5 22.5 22.5 -c 1593 1596 -t 1591 -x A:CYS164 -o 3c9w_cov_cmdline

MSMSLIB 1.4.4 started on fiji.scripps.edu

Copyright M.F. Sanner (March 2000)

Compilation flags 

#################################################################

# If you used AGFR in your work, please cite:                   #

#                                                               #

# P.A. Ravindranath S. Forli, D.S. Goodsell, A.J. Olson and     #

# M.F. Sanner                                                   #

# AutoDockFR: Advances in Protein-Ligand Docking with           #

# Explicitly Specified Binding Site Flexibility                 #

# PLoS Comput Biol 11(12): e1004586                             #

# DOI:10.1371/journal.pcbi.1004586                              #

#                                                               #

# <PAPER TO COME> and                                           #

#                                                               #

# P. Ananad Ravindranath and M.F. Sanner                        #

# AutoSite: an automated approach for pseudoligands prediction  #

# - From ligand binding sites identification to predicting key  #

# ligand atoms                                                  #

# Bioinformatics (2016)                                         #

# DOI:10.1093/bioinformatics/btw367                             #

#                                                               #

# Please see http://adfr.scripps.edu for more information.      #

#################################################################

 

Computing grids on fiji.scripps.edu a Darwin-14.3.0-x86_64-i386-64bit computer

Date Fri Dec 16 17:56:21 2016

 

loading receptor: 3c9w.pdbqt

set box using user

    Box center:    28.565     6.329     6.985

    Box length:    22.500    22.500    22.500

    Box size  :        60        60        60

    padding   :     0.000

    spacing   :     0.375

 

setting map types using: all to ['HS', 'Mg', 'HD', 'NA', 'Fe', 'Br', 'NS', 'A', 'C', 'Mn', 'G', 'F', 'I', 'H', 'J', 'N', 'Q', 'P', 'S', 'GA', 'Z', 'Zn', 'Cl', 'Ca', 'OA', 'SA', 'OS']

 

computing maps for center=(28.565 6.329 6.985) size=(22.500 22.500 22.500) dims=(60 60 60) ...

    maps computed in 18.66 (sec)

the following 33 covalent ligand atoms did not contribute to the grid calculation:

    A:CYS164:CA,CB,SG,O23,C7,O8,C9,C25,C10,C11,C12,C2,C1,O20,H20,C6,C5,O21,C22,C4,C3,C18,O31,C17,C16,C15,O29, H29,C14,O28,H28,C13,O24

making target file 3c9w_cov_cmdline.trg ...    done.

done. 24.73 (sec)

 

Explanations:

After reading the receptor a box is set up around the ligand with the position and size that were specified manually.

set box using user

    Box center:    28.565     6.329     6.985

    Box length:    22.500    22.500    22.500

    Box size  :        60        60        60

    padding   :     0.000

    spacing   :     0.375

The affinity maps are computed for all AutoDock4 atom types.

setting map types using: all to ['HS', 'Mg', 'HD', 'NA', 'Fe', 'Br', 'NS', 'A', 'C', 'Mn', 'G', 'F', 'I', 'H', 'J', 'N', 'Q', 'P', 'S', 'GA', 'Z', 'Zn', 'Cl', 'Ca', 'OA', 'SA', 'OS']

The maps are computed.

computing maps for center=(28.565 6.329 6.985) size=(22.500 22.500 22.500) dims=(60 60 60) ...

The atoms not contributing to the grid are listed next

    the following 33 covalent ligand atoms did not contribute to the grid calculation:

      A:CYS164:CA,CB,SG,O23,C7,O8,C9,C25,C10,C11,C12,C2,C1,O20, H20,C6,C5,O21,C22,C4,C3,C18,O31,C17,C16,C15,O29,H29,C14,O28,H28,C13,O24,

Finally, a file containing the maps, the receptor and meta data is created.

    making target file 3c9w_cov_cmdline.trg ...    done.