LMOD (Recipe)
Ingredients:
1 Macromodel .dat file,
1 Batchmin job control template file.
Instructions:
Convert the Macromodel .dat file to a Tripos .mol2 file.
Use the modeling tool of your choice (Sybyl, Wit!P, ...) to define the
following
static atomsets:
mobile |
atoms that are free to move |
fixed |
atoms that are fixed at their initial position |
comparison |
atoms to be used for comparing minimized structures (max. 200 atoms) |
chiral |
atoms for which configuration (chirality) must be preserved |
mols |
1 atom from each independently rotated/translated molecule |
Use the preLMOD Perl script to generate a Batchmin job control file
and a substructure definition file (.sbc) from the .mol2 file and the template
file:
$ preLMOD -c template jobname
Put into the oven and bake for a couple of days:
$ batchmin jobname
Enjoy!
Notes:
-
Macromodel .dat files may be converted to Tripos .mol2 files using the
mmodmol
utility
$SCHRODINGER/utilities/mmodmol < input.dat
> output.mol2
or by reading the .dat file into Wit!P, and writing it out in mol2 format.
-
If Wit!P is used to generate the .mol2 file from a Macromodel .dat file,
it is usually a good idea to write a new Macromodel .dat file from the
.mol2 file, to make sure that the atom order in the two files is consistent.
This may be necessary since Wit!P has some restrictions on the order of
atoms in a molecule (atoms of the same residue must have contiguous order),
and may change the atom order if the original .dat file does not comply
with these restrictions.
-
Only one of the sets mobile and fixed needs to be specified.
If neither set is defined, all atoms are assumed to be free to move.
-
The comparison set defines up to 200 atoms. The atoms in this set
will be used to compare minimized structures with all previous unique minima
found. Structures for which all pairs of equivalent atoms are within a
threshold defined by the Batchmin CRMS command (default: 0.25 Å)
after least squares superposition are considered to be the same, and only
the one with the lower energy will be retained. It is not necessary to
specify all atoms in the system for comparison, but a representative sampling
from widely separated atoms should be included in this set. If no comparison
set is defined, LMOD will not attempt to eliminate duplicate minima.
The definition of the comparison set alone is not sufficient to allow
the elimination of all duplicate minima, if the set contains atoms which
have symmetrically equivalent atoms in the mobile atomset (e.g. the three
hydrogen atoms in methyl, or the two oxygen atoms in carboxylate). In this
case the job control file generated by preLMOD may be manually augmented
with
ATEQ, NSEQ, NSRO or NSRF commands, defining groups of
equivalent atoms, or automatic symmetry detection features may be used
in newer versions of Batchmin (c.f. BatchMin Reference Manual, current
version). Alternatively, the MSYM command may be used, which makes
the use of ATEQ, NSEQ, NSRO and NSRF commands unnecessary
(MSYM is a new feature introduced in Macromodel 8).
-
LMOD will compute improper torsions with the first three substituents of
atoms included in the chiral atomset. These "chirality" descriptors
will be stored for the first structure in the input file. All subsequently
generated structures will be checked against "chirality" changes, and rejected
if such changes are detected. The comparison set should therefore include
all chiral centers which are connected to atoms in the mobile atomset.
-
The purpose of the mols atomset is to select molecules to be independently
rotated and translated during the LMOD search. In most docking applications,
where a single ligand is being docked into a target binding site, this
set will consist of a single ligand atom.
-
The preLMOD Perl script generates job control (.com) and substructure
definition (.sbc) files. The .com file is generated from a template by
replacing COMP, CHIG, and MOLS commands by corresponding
new commands, using the atomset definitions from the Tripos MOL2 file.
ATEQ,
NSEQ, NSRO and NSRF commands in the template job control file
will be ignored. The .sbc file will be generated from the definitions of
the mobile and/or fixed atomsets in the MOL2 file.
The use of a job control file template is optional. If no template is specified
on the preLMOD command line, a job control file with standard LMOD commands
will be created from scratch. The file may be modified as needed, and used
as a template file in subsequent preLMOD commands.
-
Hint: use the mmread command in the Confa menu of Wit!P to
view old-style (mmio) multi-conformer .dat files generated by Batchmin/LMOD.
New-style (m2io) multi-conformer files can not be read by mmread.
These files may be converted to Wit!P .cnf files using the mae2cnf
Perl script.
See also: LMOD Tutorial
A.Widmer,
NIBR/CPC/CSG-SB