14. Using AutoTors to Define Torsions in the Ligand

This section describes input and output files used and generated by AutoTors . Input consists of one or two files, depending on whether the ligand is in our " AutoDock -standard" PDBQ-format, or in Sybyl's mol2 -format. PDBQ-format is the default; mol2 -format is allowed with the " -m " flag (see below).

Ligand is in PDBQ-format:

When the ligand is in PDBQ format, AutoTors also needs a "bnd" or bond file, which describes the connectivity of the atoms in the ligand. In this example, the bond file is "oligo.bnd", and "oligo.pdbq" is the input PDBQ file; "oligo.out.pdbq" is created and contains all the ROOT, BRANCH and TORS keywords needed to define the torsions selected by the user.

 
% autotors oligo.bnd oligo.pdbq oligo.out.pdbq

The ".bnd" file, contains information about the covalent bonds in the ligand. The bonds are described by the serial numbers of the atoms in the input PDBQ file, with one line per bond. For example, if C10 is the atom appearing on the first "ATOM" line in the PDBQ file, and it is bonded to N18 which appears on the 17th line in the PDBQ file, this information appears as a discrete line in the ".bnd" file as: "1 17". The output of "pdbtoatm" is an "atm" file, which can be converted to a "bnd" file, using "atmtobnd". For example, to generate a "bnd" file, use something like this command:

 
% pdbtoatm vitc.pdbq | atmtobnd > vitc.bnd

Ligand is in Mol2-format:

When the ligand is in SYBYL-mol2 format, no "bnd" bond file is required, in addition to -m flag. This is because the mol2 file contains both atom coordinates and bonding information. So, for example the following command would read in the "lead.mol2" file and after interactively requesting which torsions to rotate, AutoTors would write out "lead.out.pdbq":

 
% autotors -m lead.mol2 lead.out.pdbq

AutoTors Output:

The output filename is defined by the last AutoTors command-line argument. Output consists of PDBQ-formatted lines, rearranged as required by AutoDock, according to the user's specification of the fixed ROOT portion of the molecule, and the allowed rotatable bonds in the rest of the molecule. AutoTors inserts the ROOT, ENDROOT, BRANCH, ENDBRANCH, TORS, and ENDTORS lines in the necessary places.

AutoTors Flags:

 
-m <input_ligand_mol2_file>

This flag is used when the input file is in Tripos 'mol2' format (produced by SYBYL). When it is entered on the command line, the program uses only 1 file for both kinds of input (the bond data input file and the pdbq data input file) and uses the second file specified for output. [If the user runs the program with the -m flag AND three file parameters on the command line, the first file will be opened for reading the input needed by the program, the second opened for writing and the third ignored. This means any contents in the second file will get over-written and lost.]

 
-h

This flag causes the program to detect non-polar hydrogens, that is hydrogen atoms bonded to carbon atoms, to merge the charge of each with the charge of the carbon to which it is bonded and to delete the line of output data pertaining to that hydrogen. At the end of the program, a count of the number of non-polar hydrogens which have been merged in this fashion is written to the screen.

 
-o

This flag is used only in conjunction with the -h flag when the pdbq data is in the older pdbq format. It causes the program to obtain charge data from column 55 instead of column 70. (Its use along with the -m flag is an error but this is disregarded.)

 
-a

This flag instructs AutoTors to disallow torsion rotations in amide and peptide bonds, (C=O)--(NH).

 
-b

This flag is useful for peptides. It disallows rotations in backbone torsions, including phi, psi and omega (peptide) torsions.

 
-c

This will add atom connectivity to the ATOM records in the output pdbq file.

 
-e

This instructs AutoTors to use the atom types given in the mol2file. This can only be used with the '-m' mol2-format flag.

 
-r

This sets the ROOT to be the non-hydrogen atom closest to the center of the molecule.

 
-M

This instructs AutoTors to use the ROTATABLE_BOND and ANCHOR information in a Tripos SYBYL mol2 formatted file, to define the ROOT and active torsions.

 
-A
-A +<angle>

This flag causes the program to check rings for aromaticity. If all the ring atoms are 'co-planar' enough, the program replaces 'C' by 'A' for all carbons in the ring. This distinction is necessary in the AutoDock 3.0 Force Field computations. By default, the test for planarity is whether the angle between two adjacent atoms' normal vectors is less than or equal to 7.5 degrees.

The user can specify what cut-off to use (and thus override the default of 7.5 degrees) by typing in a different angle after the -A flag. The angle should be given in degrees. Note: this number must be preceeded by a plus sign, '+'. For example:

 
% autotors -A +6.2 myfile.bnd myfile.pdbq myfile.out

would cause autotors to use 6.2 degrees for this aromaticity cut-off angle between adjacent atoms. This depends on how 'warped' the ring is: some crystal structures can have aromatic rings that are quite distorted from planarity.

The -m , -h and -a flag may appear in any order. The -o flag must be given after the -h flag. Placement of these flags should follow these two examples. Square brackets denote optional flags: 

 
% autotors [-h][-o][-a][-c] pept.bnd pept.pdbq pept.out.pdbq

For SYBYL-mol2 input, e.g. :

 
% autotors -m [-h][-o][-a][-c] drug.mol2 drug.out.pdbq