OptLigandInDU

Overview

OptLigandInDU is an application to optimize a ligand or a series of ligands in a rigid protein active site.

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

Ligand Optimization in a protein active site

Optimizes the Ligand(s) in a protein active site using FF14SB-Parsley Force Field.

Input files

  • 1H1Q_AB_receptor.oedu : OEDU file containing the protein active site.
  • 1H1Q_AB_fred_docked.oeb : OEB file containing the ligand to optimize.

Command line

prompt> optligandindu 1H1Q_AB_receptor.oedu 1H1Q_AB_fred_docked.oeb 1H1Q_AB_fred_docked_opt.oeb

Output files

  • 1H1Q_AB_fred_docked_opt.oeb : OEB file containing optimized ligands.

Optimize a Ligand pose in a rigid protein

Performs a constrained optimization of the ligand in the rigid protein active site, using FF14SB-Parsley Force Field.

Input files

  • 1H1Q_AB_receptor.oedu : OEDU file containing the protein active site.
  • 1H1Q_AB_fred_docked.oeb : OEB file containing the ligand to optimize.

Command line

prompt> optligandindu -du 2IKO.oedu -in 1H1Q_AB_fred_docked.oeb -out 1H1Q_AB_fred_docked_opt.oeb -optimize poseCartesian

Output files

  • 1H1Q_AB_fred_docked_opt.oeb : OEB file containing optimized ligand.

Command Line Help

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

> optligandindu --help

will generate the following output:

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

Required Parameters

-du <filename>

An OEDU file with a design unit, containing the protein active site. If the file contains multiple design units, only the first one is used.

[keyless parameter 1]

-in <filename>

Molecular input file name containing 3D coordinates in any format supported by OEChem.

[keyless parameter 1]

Acceptable molecule file formats are:

SZYBKI file format support
File extension Description
mol MDL Mol File
mmd, mmod Macromodel
mol2 Tripos Sybyl mol2 file
oeb New Style OEBinary
sd, sdf MDL SD File
xyz XMol XYZ format

Optional Parameters

Input Options

-molnames

This parameter specifies 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 database, without having to extract those molecules by hand from the database.

Output Options

-out <filename>

Output file name, in any format supported by OEChem, for an optimized ligand.

[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.