DOCK6 Amber Score Custom Input Preparation

Author: Scott Brozell
Last updated January 27, 2023 by Scott Brozell

This tutorial describes the preparation of DOCK Amber score input files for receptors containing custom residues. These techniques should be applicable to any receptor-ligand system. Docking and rescoring studies for a protein containing phosphotyrosine are the basis.

Input files preparation.

1) Ligand Preparation: Follow the procedure described in Step 1) of the Overview and Input Preparation Amber Score tutorial.

2) Receptor Preparation:

Follow the procedure described in Step 2) of the Overview and Input Preparation Amber Score tutorial.

There are additional steps for recognition of custom residues by the command prepare_amber.pl. In this tutorial the receptor has phosphotyrosine residues (named PTR in the PDB file) in its active site, and initially these are not recognized by the program.

The methodology for handling this type of situation was added in Dock 6.2. The general procedure is to determine how one would recognize phosphotyrosine in Amber. And then to add the appropriate commands into dock6/parameters/leap/cmd/leaprc.dock.user, which is a user library that is automatically processed; see the Amber Score Inputs documentation.

Inserting phosphotyrosine into the Amber search bar finds a gem: https://archive.ambermd.org/200707/0284.html. The "contributed parameters" url is https://www.pharmacy.manchester.ac.uk/bryce/amber. Parameters for both phosphotyrosine with a single protonated phosphate group and phosphotyrosine with an unprotonated phosphate group are listed.

As described in general in the Amber score tutorial one must ensure that the phosphotyrosine residue names in the PDB file, in this case PTR, match those in the Amber parameter files, Y2P for the unprotonated one above; ie, edit your PDB and change PTR to eg, Y2P.

Add the LEaP commands into dock6/parameters/leap/cmd/leaprc.dock.user: loadamberparam frmod_y2p loadOff Y2P.off

prepare_amber.pl should now automatically recognize phosphotyrosine. Be sure to examine the amberize*.out and *.log files for warnings and errors; see the Amber Score in Practice documentation.