spruce4docking tutorial

The first step in using FRED, HYBRID or POSIT is the creation of an OEDocking receptor, a collection of docking related information connected to a protein. A typical receptor (as viewed in VIDA) is shown in figure OEDocking receptor and typical docking information.

OEDocking receptor

OEDocking receptor and typical docking information

An OEDocking receptor includes the protein structure and a description of the binding site. This description includes a so called outer contour that indicates where heavy atoms are to be placed during FRED, HYBRID or POSIT ’s search procedures.

A pose receptor traditionally includes a bound ligand used to help identify existing binding modes, and may include so called extra molecules which are interesting items such as waters and solvents that have been stripped for the purposes of docking.

While there are several ways to make receptors, POSIT has a simplified, easy to use command line utility, Spruce4Docking.

The most complicated portion of making pose receptors is identifying the bound ligands. If Spruce4Docking is run with only an input protein file, it attempts to automatically identify the ligand(s) and outputs receptors for each.

> spruce4docking –in renin/5TMG.pdb.gz -map renin/5tmg.mtz

This command creates the following OEDocking receptor files:

  • rec_5TMG_A__DU__7EK_A.oeb.gz
  • rec_5TMG_B__DU__7EK_B.oeb.gz

The reason for the two receptors, is that the asymmetric unit in the PDB file contains two instances of the biological unit. The electron density map (mtz file) is optional, however, when supplied the Iridium category of each receptor is being evaluted and written in sorted order for use with docking.

The same receptors could also have been created by explicitly listing the residue on the command line. However, this should only be used when autodetection fails, or when multiple different ligands are present and only one is desired.

> spruce4docking in renin/2IKO.pdb.gz -map renin/5tmg.mtz -ligand_names 7EK

See the Spruce4Docking section for more details, including how to more explicitly control output file names.