phase_align_core Command Help
Command: $SCHRODINGER/utilities/phase_align_core
phase_align_core - Combines constrained conformational sampling with shape
similarity to superimpose a set of ligands onto a rigid template in a consistent
manner.
Usage: phase_align_core <template> <ligands> [options]
<template> - Maestro or SD file containing a single 3D template structure to
which the ligands are to be aligned.
<ligands> - Maestro or SD file containing the ligand structures. By default,
the largest Bemis-Murcko scaffold that is shared by a given ligand
and the template is identified and treated as the common core. The
internal 3D coordinates of the ligand core atoms are reset to match
those of the template, and the ligand is aligned to the template on
the core atoms. Constrained conformational sampling of the ligand
is then performed with the common core held fixed. The conformer
that yields the highest overall shape similarity to the template is
selected.
Aligned ligands are written to <jobName>_align.maegz, where <jobName> is the
base name of the ligands file.
Options: [[-fuzzy <level>] [-noscaff standard|skip] | -core <smarts> |
-mcs <pwFile> [-titles] | -atoms <listFile>]
[-save <mapFile>]
[-hydrogens 0|1|2]
[-atomTypes mmod|element|qsar]
[-close <tol>]
[-openrings skip|allow]
[-fail force|standard|skip | -harsh]
[-nocarry]
[-noflex]
[-sample rapid|thorough|rdkit]
[-max <numConfs>]
[-ewin <deltaE>]
[-terminal sample|align]
[-skip <maxRot>]
[-time <tlimit>]
[-verbose]
[-JOB <jobName>]
[-HOST <host>]
[-LOCAL]
[-TMPDIR <dir>]
[-WAIT]
[-NICE]
[-NOJOBID]
-fuzzy <level> - Use fuzzy matching when identifying the largest
common scaffold:
<level> Meaning
1 Treat all heavy atoms and bonds as
equivalent.
2 Distinguish aromatic from non-aromatic
atoms.
3 Distinguish single, double, triple,
and aromatic bonds.
Regardless of the fuzzy matching level, ring
atoms are distinguished from linker atoms.
-noscaff standard|skip - Action to take when the ligand and template
contain no common scaffolds:
standard - Perform a standard shape-based
alignment of the overall structure.
This is the default.
skip - Skip the ligand altogether.
When standard shape-based alignment has to be
done, the output structure will contain the
property s_phase_Align_Method, and its value
will be "standard".
-core <smarts> - Use the supplied SMARTS or SMARTS-containing
file to define the common core for each ligand-
template pair. If <smarts> is a file, it must
contain one SMARTS per line, with the number of
lines being equal to the number of ligands. A
given SMARTS must produce at least one match to
the corresponding ligand and to the template.
-mcs <pwFile> - Extract common cores from the pairwise MCS
output file written by canvasMCS when -opw is
used. Note that <pwFile> must contain results
for the template and all ligands to be aligned,
and that structures in <pwFile> are identified
by canonical SMILES, which means there can be
no duplicates. It is strongly recommended that
the following canvasMCS options be used:
-atomtypes 7 -nobreakring -nobreakaring
-titles - Identify structures in <pwFile> based on their
titles. This allows duplicate structures to be
processed as long as they have distinct titles.
-atoms <listFile> - Align ligand-template pairs according to the
atom lists in the supplied file. Each line of
<listFile> must contain two comma-separated
lists of atoms, with one or more spaces between
the lists. The first list corresponds to the
template, and the second list corresponds to
the ligand being aligned to it. For example,
9,10,11,12,13,14,17,18 1,2,3,4,5,6,10,11
9,10,11,12,13,14 17,18,19,20,21,22
7,8,9,10,11,12,13,14 3,4,5,6,7,8,9,10
etc.
The first line indicates that ligand atom 1
should be aligned to template atom 9, ligand
atom 2 should be aligned to template atom 10,
etc. Note that atom numbering starts at 1.
-save <mapFile> - Write common core SMARTS and atom mappings to a
file. <mapFile> will contain one line for each
ligand, with the following format for the Nth
ligand:
N. <SMARTS> <template> <ligand>
<template> and <ligand> are comma-separated
lists of the atoms matched in the template and
ligand structures, respectively. Not valid with
-atoms <listFile>.
-hydrogens 0|1|2 - Hydrogen overlap treatment:
0 - Ignore all hydrogens.
1 - Consider only polar hydrogens.
2 - Consider all hydrogens (default).
-atomTypes mmod|element|qsar - Consider atom types when computing shape
similarities. The supported atom typing schemes
are:
1. mmod - MacroModel atom types.
2. element - Elemental types.
3. qsar - Phase QSAR atom types:
D - H-bond donor hydrogen
H - hydrophobic/non-polar
N - negative ionic
P - positive ionic
W - electron-withdrawing
X - other
-close <tol> - Non-bonded close contact distance. If <tol> is
greater than 0, each snapped ligand structure
will be checked to see if it contains any close
contacts that were not present in the original
ligand structure. An alignment will be rejected
if a new close contact is created. The default
is 1.0.
-openrings skip|allow - Policy with regard to ligand mappings that
contain an incomplete ring, such as only three
atoms in a cyclohexane. Snapping the core in
these cases almost always results in a badly
distorted ring. The default is "skip".
-fail force|standard|skip - Action to take when all mappings are rejected
due to open rings, or when the ligand core
cannot be snapped onto the template without
altering the ligand's stereochemistry or
creating close contacts:
force - Perform a least-squares alignment
based on the core atoms. This is the
default.
standard - Perform a standard shape-based
alignment of the overall structure.
skip - Skip the ligand altogether.
When a ligand has to be aligned via either of
the first two methods, the output structure
will contain the property s_phase_Align_Method,
and its value will be or "force" or "standard".
-harsh - Stop processing and return an error code to the
shell if a ligand core cannot be snapped onto
the template for any reason. Incompatible with
-fail.
-nocarry - Move only the ligand core atoms when snapping
the ligand core onto the template. This can
result in badly distorted structures, so use
with caution. Note that the non-core atoms can
still move during conformational sampling, so
if the entire ligand structure is to remain
rigid after snapping, use -noflex.
-noflex - Do not perform conformational sampling after
snapping ligand core into place. If this flag
is used, all conformational sampling options
are ignored.
-sample rapid|thorough|rdkit - Conformational sampling method. The default is
thorough.
-max <numConfs> - Maximum number of conformers to generate for
each ligand. The default is 1000.
-ewin <deltaE> - Conformational energy window in kJ/mol. The
default is 16.0.
-terminal sample|align - Whether to conformationally sample rotatable
terminal atoms (e.g., -CH3, -NH2, -OH) if they
are part of the core, or align their closest
pairs of hydrogens. Irrelevant when cores are
Bemis-Murcko scaffolds since rotatable terminal
atoms are excluded from Bemis-Murcko scaffolds.
The default is to align hydrogens.
-skip <maxRot> - Do not attempt conformer generation on ligands
with more than <maxRot> rotatable bonds. The
default is 25.
-time <tlimit> - CPU time limit in seconds for ligand conformer
generation. If the time limit is exceeded, the
best superposition found up to that point is
retained, the output structure will contain the
property b_phase_Time_Exceeded, and its value
will be true. The default is no time limit.
-verbose - Verbose output to log file.
-JOB <jobName> - Job name. The default is to use the base name
of the ligands file.
-HOST <host> - Run job on <host>. Only single-CPU jobs are
supported.
-LOCAL - Store temporary job files in current directory.
-TMPDIR <dir> - Store temporary job files in <dir>.
-WAIT - Do not return prompt until job completes.
-NICE - Run job at reduced priority.
-NOJOBID - Do not run under Schrodinger job control.