Bindres

Table of contents

Top

Introduction

The Binding Response, first described in ref. [1], is a method to select binding sites on a protein for virtual database screening. As outlined in ref. [1], Scheme 1, it involves several steps, performed by different computational chemistry programs. Shijun Zhong provided a script named br.csh that calls all these programs in order and does the necessary format conversions. The present script, bindres, was written by Kenno Vanommeslaeghe. It essentially replicates the behavior of br.csh , but is more flexible.
Top

Summary of new features:

Top

Installation

In principle, it suffices to untar the "Binding Response" distribution and to set an environment variable "brdir" that points to the installation directory. For example:
cd
gunzip -c binding_response.tar.gz | tar xf -
echo "brdir=$HOME/binding_response" >> .profile
echo "export brdir" >> .profile
. .profile
All bindres-related files are in the subdirectory bindres . Bindres calls the following binaries: It searches for these binaries in $brdir/bin (or $brbin, if it is set) and $PATH .

Note: dms generally won't run if not properly installed; ie. just copying the binary to another machine doesn't work. Also, different versions of DMS often give slightly different results. During some test runs, even the same version of DMS gave different results on different architecures.
Note: only limited testing was performed with versions of Dock other than Dock 4.0. In general, different versions produce different results. Also, the current grid.in and dock.in are not compatible with Dock 6 and should be edited if used with this version.
Top

Usage

Invoking bindres without any arguments prints the following instructions:
Generates sphere clusters on a protein surface and performs docking on them.

Usage: bindres [-t <top>] [-c <col>] [-f] [-e]
[-b '<binding sites>'] [-l <ligand[%]>] [-p <nproc>] [-n]
[-o <orderly>] [-s] <pdb file> [<mol2 file> [<library>]]

Where: <pdb file> does not have hydrogens
  (it is recommended to add the suffix "_noh")
       <mol2 file> does have hydrogens and Gasteiger charges. If this file is
  omitted, the program will gracefully exit after saving the top <top> sphere
  clusters.
       <library> is a mol2 library of compounds to dock. If omitted, the
  program will gracefully exit after generating the docking grids. If <library>
  is not found on the specified location (relative to the current working
  directory), the program will search for it in the installation directory.
  For example, specifying "ligand1000.mol2" reproduces the behavior of the
  original binding response script.
       -t <top> is the number of sphere clusters (ie. binding sites) to save.
  Default=10.
       -c <col> is the column in the .cst file on which to prioritize
  the sphere clusters (ie. binding sites).
             Possible values: 2 = the number of spheres (default)
                              3 = the standard deviation
                              4 = the maximum distance
       -f force redoing the whole procedure. If this switch is not present, the
  program will try to re-use any files already present on the system.
       -e request extra output, ie. an ascii file to make a histogram of the
  clusters and a pdb file containing only the centers of the clusters.
       -b '<binding sites>' selects the binding sites (ie. sphere clusters)
  used for docking by means of a space-separated list of 3-digit numbers
  enclosed within single quotes. If -b is omitted, the program will prompt for
  a selection, allowing the user to visually examine the sphere clusters first.
  Wildcards are allowed.
  Examples: -b '???' selects all binding sites, reproducing the behavior of the
  original binding response script.
            -b '0[01][0-9] 020' selects binding sites 000-020. Note that the
  highest ranking binding site is designated 001, so 000 is silently ignored.
       -l <ligand[%]> is the number of ligands used to calculate the final
  binding response for each binding site. I followed by a % sign, it designates
  a percentage of <library>. Default: 90% if <library> contains 100 compounds
  or more, otherwise 100% .
       -p <nproc> is the number of sites to dock simultaneously. Default=1.
  Setting this to the number of processors in your machine is not always a good
  idea; if you have multiple processors, you may still want to use "-p 1" and
  specify "parallel_jobs yes" in your dock.in file instead.
       -n run dock now. Docking is started on the background. If this switch is
  not present, a shell script for running dock will be created but not started.
       -o <orderly> controls to which extent the output files of the different
  programs are cleaned up. Possible values:
             0 = leave everything
             1 = leave the files needed to restart the procedure from any point
                                                                      (default)
             2 = reproduce the behavior of the original binding response script
                                                     (not optimal for bindres!)
             3 = delete everything except the final report (not recommended!!!)
       -s create a separate script for calculating the binding response.
  If this switch is not present, the docking script will take care of this.
  Note that it *generally* doesn't make sense to combine this switch with -n.

Example: bindres -feno 2 -b '*' protein.pdb protein.mol2 ligand1000.mol2
  Will reproduce the behavior of the original binding response script, except
  that it works in any directory, that the input files can have a different
  name than "protein", and that a different directory structure is created.
Top

Details

Methodology

This section is a step-by-step description of the procedure, including the effect of the different command-line parameters.

Bindres will:

Remarks:

Top

breport

breport is a self-contained script, which can be called from the working directory as follows:
breport <subdir>
, where <subdir> is the subdirectory.

breport copies the draft report generated by bindres from the subdirectory to the working directory and appends a table of binding responses, optionally recalculating the binding response using only a subset of the ligands. Specifically, it uses the <ligand[%]> ligands with the best binding response, where <ligand[%]> is determined by bindres' -l option (<ligand[%]> is passed from bindres to breport via the .par file). Recalculating the binding response with a different subset can be accomplished either by editing the .par file (not recommended because the table will not be consistent with the part that was copied from the draft report) or rerunning bindres with a different -l value and without the -f switch.
Top

Environment variables and files

Bindres searches for files at different locations. This process is controlled by environment variables. Bindres needs $brdir to point to the binding_response installation directory. It accesses the following subdirectories: Top

References

[1] S. Zhong, Alexander D. MacKerell Jr., J. Chem. Inf. Model. 2007, 00, 0000-0000.
Top