OptimizeDU

Overview

OptimizeDU is an application to optimize a protein-ligand complex inside a design unit.

This application currently do not have the option to include solvent effects during the optimization. It is recommended that a single point SZYBKI calculation be performed after optimization to estimate the solvent effect.

Complete optimization including solvent effects would be incorporated in a future release of this application.

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

Input Options

-molnames

This parameter specifies a text file containing a list of design unit names (one name per line in the file). If this parameter is set then only design units 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 design unit(s) that are contained in a large database, without having to extract those design units by hand from the database.

Output Options

-out <filename>

An OEDesignUnit file containing the optimized protein-ligand complexes.

[keyless parameter 2]

-prefix

Prefix used to name output files.

-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]

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.

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).