Input Preparation

Note

It is not required to calculate the ligand charges and protein charges explicitly. The scoring functions do not utilize partial charges.

Ligand Preparation

The most common use of HYBRID is to dock a large collection of molecules into the active site of a target protein. For the purposes of this document, we’ll call the file(s) of molecules the database file(s), or dbase file(s). The most common format for database file(s) is a multi-conformer OEBinary file created by OpenEye’s OMEGA program, however, this file can be one of several 3D formats. These formats include SDF, MOL2 and PDB. HYBRID determines the database file format from the file extension, .sdf or .mol for SDF, .mol2 for MOL2, .pdb or .ent for PDB. Gzip compressed files of these same formats are allowed as well. HYBRID will interpret infile.sdf.gz as a gzip’ed SDF file.

Note

Note that even though all these formats are supported, using SDF, PDB or MOL2 can result in a loss of speed due to the I/O penalty of these formats.

HYBRID has no provision for conversion of 1D/2D molecules to 3D. The database file(s) must be in a conformationally expanded 3D format. Within the OpenEye tool chain the program OMEGA can be used to convert 1D/2D to 3D and generate conformers.

By default HYBRID will interpret conformers in the database file(s) as part of a single multi-conformer molecule as long as they:

  • Are contiguous in the input file.
  • Have the same numbers of atoms and bonds in the same order
  • Have identical atom and bond properties with their order correspondent in the subsequent connection table
  • Have the same atom and bond stereochemistry

While this may appear to be a restrictive list, many programs write multi-conformer molecules into SDF or MOL2 files such that the above rules will be satisfied. If the conformers are named differently, (i.e. they have a conformer number appended to the base name like acetsali_1, acetsali_2), HYBRID will still consider them part of a single multi-conformer molecule if the criteria above are met. For file formats that are not inherently multi-conformer, this behavior can be turned off or modified with the -conftest command-line switch.

Receptor Preparation

HYBRID can use either a single receptor or multiple receptors each of which contains a different structure/conformation of the target protein. Each receptor must also have a bound ligand. Receptors with bound ligands can be created with the following programs.

Program Type Description
MakeReceptor GUI Interactive GUI for creating a receptor.
Pdb2Receptor Command Line Creates a receptor from a PDB file with a protein-ligand complex.
ReceptorSetup Command Line Creates a receptor from a molecule file with a protein and a separate file with either the structure of a bound ligand or a box enclosing the active site.

Note

Receptors can also be created using the Docking Toolkit (see the Docking Toolkit documentation).