makefraglib: Creating a Fragment Library
makefraglib identifies, extracts, and generates conformers of
molecular fragments. The model builder in OMEGA fragments input
molecules, retrieves corresponding fragment conformers, and assembles
them into a three dimensional structure. Pregenerating fragment
conformers using makefraglib accelerates the model building
The model builder in OMEGA attempts to capture all of the relevant
bond length and angles, and ring conformations for an input molecule.
Fragment assembly allows for a ‘divide and conquer’ approach to model
building. Much of the relevant information for building a molecular
models is contained in carefully chosen fragments. makefraglib
uses distance constraints and geometry optimization to generate
fragment conformations. Only a single conformation is stored for
acyclic fragments, while all possible unique ring conformers are
retained within user defined limits. Libraries created with
makefraglib can then be provided to OMEGA using the
-setfraglib or -addfraglib flags.
makefraglib can be used from the command-line to generate ring
templates for use with OMEGA starting from only a collection of
molecules. The output file from makefraglib can then be passed
directly into OMEGA using the -setfraglib or -addfraglib
flag. Although fragment libraries may be concatenated using the Unix
‘cat’ command, this is not strictly necessary as multiple fragment
libraries may be specified as one argument to the flag.
- File containing one or more molecules from which fragments will be generated
- File to write fragments generated by makefraglib. OEBinary format is required and Gzipped OEBinary is recommended.
- The argument for this flag is the name of a
file containing control parameters. The control parameter file acts
to either replace or augment the command line interface. All
parameters necessary for program execution may be provided in the
control parameter file, although any command given explicitly on the
command line will supersede options found in the parameter file.
The application generates a new parameter file containing the full set of
execution parameters upon every execution. The name of the
parameter file is created by combining the prefix
base name with the ‘.parm’ extension.
- Specifies the number of processors n when the application is run in MPI mode.
- Specifies the name of the file containing processors configuration. For every host
this file should contain a line host_name slots=n where n is the number of
processors on the host.
- The argument for this flag specifies the name of
the log file. The level of detail for logfile information can be
altered using the -verbose flag. Output can
be directed to the terminal instead of a file by giving a hyphen ‘-‘
as the argument to the flag instead of a filename. Generation of an
output log may be disabled by providing ‘nul’ or ‘null’ as an
argument. [default = prefix.log]
- The argument for this flag defines the prefix to be used
for various information and data files generated by OMEGA. Most
important among these is the ‘makefraglib.parm’ file which includes a
copy of all the parameters used in the makefraglib run. The prefix is
also used to generate a default log file name if not explicitly
specified with the -log flag. [default = makefraglib].
- Show progress on screen. Options are ‘none’, ‘dots’, ‘log’ and ‘percent’.
The ‘dots’ options will displays dots on screen to show molecules
completed. The ‘log’ option will duplicate the log file on screen.
The ‘percent’ option will track progress through the input file. [default = none]
- Existing fragment library to avoid duplicating
- This is a boolean flag that controls the level of
detail written to the log file. [default = false]
3D Construction Parameters
- This flag sets the force field used for
constructing fragments that are assembled to build an initial model
of the input structure. Consult the description of Force Fields
(see Force Fields) for an explanation of appropriate
arguments for this flag. [default = mmff94s_NoEstat]
- The -ewindow flag sets the energy window used
as an accept or reject criteria for fragments. Any fragment that
has a calculated strain energy less than the sum of the energy
window and the energy of the global minimum fragment will be
accepted. Conformers with strain energies above this threshold are
rejected. [default = 4.0]
- This boolean flag determines whether makefraglib should
generate an initial set of 3D coordinates using only the connection
table of the input molecule. Initial model generation is always
necessary for molecule file formats devoid of coordinates (i.e
SMILES). Bond lengths and angles taken from molecule files
containing coordinates may be retained by setting this flag to
false. [default = true]
- The -rms flag sets the minimum Root Mean Square
(RMS) Cartesian distance below which two fragments are duplicates.
The RMS calculation is performed after superposition such that the
true minimum distance between fragments is calculated. Lowering
the -rms value may cause makefraglib to generate ensembles that
contain more fragment conformers of a similar shape. Higher
-rms values may result in smaller, yet possibly more shape
diverse ensembles. [default = 0.1]
- Factor for determining number of random starting geometries when generating fragments.
The following section shows several common command-line executions of
makefraglib. Each example is followed by an explanation of what the
program will do.
Sample data files can be found in the data directory.
prompt> makefraglib -in drugs.smi -out fraglib.oeb
All of the molecules in drugs.smi will be processed. The set of all
unique fragments (according to OMEGA fragmentation rules) from all of
the molecules in drugs.smi will be collected.
prompt> makefraglib -in vendor.smi -out new_fraglib.oeb -skip fraglib.oeb -ewindow 5.0
Conformers will be generated for all of the unique fragments found in
the user supplied file vendor.smi that are not present in fraglib.oeb. An energy
window of 5 Kcal above the global minimum conformer will be used to
accept or reject conformations of flexible ring systems.