OptimizeDU¶

Overview¶

OptimizeDU is an application to optimize a protein-ligand complex inside a design unit. This is suitable for lead optimization, where a complete optimization which includes solvent forces and possibly partial relaxation of the protein residues in the direct proximity to the ligand desired.

Example Commands¶

Protein-Ligand Optimization in a Design Unit¶

Optimizes the Protein-Ligand complex in the design unit using FF14SB-Parsley Force Field. Complete protein residues within 2 angstroms from the ligand are considered flexible by default.

Input files

1H1Q_AB_receptor.oedu : OEDU file to optimize protein-ligand complex.

Command line

prompt> optimizedu 1H1Q_AB_receptor.oedu 1H1Q_AB_opt.oedu

Output files

1H1Q_AB_opt.oedu : OEDU file containing optimized protein-ligand complex.

Optimize a Ligand pose in a partially flexible protein¶

Performs a constrained optimization of the ligand in the partially flexible protein active site, using FF14SB-Parsley Force Field. Complete protein residues within 2 angstroms from the ligand are considered flexible by default.

Input files

1H1Q_AB_receptor.oedu : OEDU file to optimize protein-ligand complex.

Command line

prompt> optimizedu -in 1H1Q_AB_receptor.oedu -out 1H1Q_AB_opt.oedu -optimize poseCartesian

Output files

1H1Q_AB_opt.oedu : OEDU file containing optimized protein-ligand complex.

Command Line Help¶

A description of the command line interface can be obtained by executing OptimizeDU with the –help option.

> optimizedu --help

will generate the following output:

Help functions:
  optimizedu --help simple      : Get a list of simple parameters
  optimizedu --help all         : Get a complete list of parameters
  optimizedu --help defaults    : List the defaults for all parameters
  optimizedu --help <parameter> : Get detailed help on a parameter
  optimizedu --help html        : Create an html help file for this program
  optimizedu --help versions    : List the toolkits and versions used in the application

Required Parameters¶

-in <filename>¶

An OEDU file containing one or more design units, containing protein and ligand.

[keyless parameter 1]

Optional Parameters¶

File Options¶

-log¶: 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. Generation of an output log may be disabled by providing nul as a argument in Windows and /dev/null as an argument on Linux and macOS. [default = prefix _log.txt]

-prefix¶: The argument for this flag defines the prefix to be used for various information and data files generated. Most important among these is the ‘prefix_parm.txt’ file which includes a copy of all the parameters used in the run. The prefix is also used to generate a default log file name if not explicitly specified with the -log flag. [default = <app_name>].

-verbose¶: This is a boolean flag that controls the level of detail written to the log file. By default only minimal information is written to the log file. Verbose logging will cause more information to be written to the log file in order to follow behavior during program execution. [default = false]

-molNames¶

This parameter takes a text file containing a list of molecule names (one name per line in the file). If this parameter is set then only molecules in the input file(s) (see parameter -in) with names that match those in the text files will be read in.

The general purpose of this flag is to provide an easy mechanism for reading a few specific molecule(s) that are contained in a large file, without having to extract those molecules by hand from the input molecules file. [default = NONE].

-progress¶: 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]

Input Options¶

-proteinMask¶

Design unit components mask defining the subset of design unit components to be used as protein during optimization. Multiple components can also be combined as a comma separated string to create the input.

Possible values = cofactors, counter_ions, excipients, lipids, metals, nucleic, other_cofactors, other_ligands, other_nucleics, other_proteins, packing_residues, polymers, post_translational, protein, solvent, sugars.

Predefined multi-component values:

targetComplex = protein,nucleic,cofactors,solvent,metals,counter_ions,lipids,other_proteins, other_nucleics,other_ligands,other_cofactors.
targetComplexNoSolvent = protein,nucleic,cofactors,metals,lipids,other_proteins, other_nucleics,other_ligands,other_cofactors.
macroMolComponents = protein,nucleic,other_proteins,other_nucleics.

[default = targetComplex]

Output Options¶

-out <filename>¶

An OEDesignUnit file containing the optimized protein-ligand complexes.

[keyless parameter 2]

Optimization Options¶

-optimize [Default: cartesian]¶: Optimization type. Choices: [0] cartesian: Performs a full cartesian optimization [1] poseCartesian: Performs a constrained cartesian optimization, ensuring to hold the ligand pose

-ff [Default: ff14sb_parsley]¶: The force field to use for optimization. A predefined force field can be used by choosing one from the list of choices. A different Smirnoff/OpenFF formatted small molecule force field can be used with ff14sb by just passing in the small molecule force field OFFXML file as the argument. Choices: [0] mmff94 [1] mmff94s [2] mmff_amber [3] mmffs_amber [4] ff14sb_parsley

-ligandCharge [Default: current]¶: Charges to be assigned for the ligand. The default value of current refers to using the existing charges on the ligand. Choices: [0] current [1] am1bcc [2] am1bccelf10 [3] mmff

-gradTol [Default: 1.0e-6]¶: Root mean squared (RMS) gradient tolerance for convergence and termination of optimization.

-maxIter [Default: 1000]¶: Maximum number of iterations for termination of optimization. Optimization is terminated if either the gradient tolerance gradTol or the maximum iterations limit, whichever occurs first, is reached.

-solventModel [Default: vacuum]¶: Solvent model to be used during optimization. Choices: [0] vacuum [1] sheffield [2] pb

Protein Flexibility Options¶

-flexRange [Default: 2.0]¶: Distance at which protein residues should be considered flexible. The distance is measured between all ligand atoms and the protein residues. The protein is completely rigid when a value of 0.0 is used.

-residueID [Default: None]¶: Regular expression (Regex) strings describing residues that should be considered flexible. When a value for residueID is provided, it overrides the -flexRange (i.e., the flexRange is ignored).