June 2009

Accelrys Discovery Studio Newsletter

Welcome!

General information on the Purpose and Content

The purpose of this newsletter is to help you get the most out of Discovery Studio. Each month a new issue of the newsletter will be published to keep you informed of upcoming events at Accelrys related to Discovery Studio/Life Sciences. In addition, there will be user tips, and protocols or scripts that can be run from the software.

News and Information	Announcing the release of Discovery Studio 2.1. here Announcing the Developer Client here Upcoming Events newsletter
DS Tips and Tricks	DS 2.0 Tip DS 2.1 Tip
Script or Protocol of the Month	Analyze Potential Binding Sites (DS 2.1 Script)
DS Community Forum Highlight	Color each of a set of molecules a unique color

News and Information

Announcing the release of Discovery Studio 2.1.

Accelrys is pleased to announce that Discovery Studio 2.1 is now available for electronic download. This release contains new scientific algorithms, improved functionality, and a large number ofcustomer suggested usability enhancements. Notable features include:

• DS Developer Client - Easily customize DS protocols/components and integrate third-party algorithms (e.g., proprietary codes, third-party codes, and access to relational databases)
• QM/MM - New science. Perform accurate optimization and single-point energy calculations using the combined power of DMol3 and CHARMm. Includes protocols and applications for structure based design and small molecule analysis.
• Scripting - Automate routine tasks and develop innovative ways to manipulate and analyze data.
• Pharmacophores - New science. Access thousands of pharmacophore models in the HypoDB database for compound activity profiling – activity, selectivity, and ADMET. Includes improved and enhanced capabilities for customizing feature definitions.
• Simulations - Calculate per-residue interaction energies and edit force field parameters interactively with updates to several protocols in structure based design. Have full access to the new version of CHARMm34b1.
• Protein Modeling - Utilize ZRANK for ranking of protein-protein docked poses generated by ZDOCK. Have full access to the new version of ZDOCK 2.3.
• Usability and feature enhancements - user-driven feedback to enhance the user interface and add scientific functionality in all areas of DS.
  
  

Upcoming Events

Discovery Studio 2.1: New Science and Customized Workflows for Drug Discovery Research Webinar series for June-July

Tips & Tricks

Tips for DS 2.0

DS 2.0 has a built in script window that greatly facilitates creating and debugging Discovery Scripts. By default if you load a perl script (file extension .pl) that script will be executed. However, if you would like to work on your own Discovery Scripts, or inspect other existing scripts you can instead lload the script into Discovery Studio and display it in a script window. To do this change the preference in Edit/Preferences .../Files Explorer/File Types. Change the default behavior for file extension ".pl" from "Run As DS Script" to "Script Window".

Tips for DS 2.1

The Discovery Studio 2.1 Script window now has a new tab called "Arguments." The values entered in this window are used as input arguments to the active script in the main script window. To use this feature, simply enter parameter values in the Arguments window separated by a space. All argument values in the Arguments window will be assigned to the perl array @ARGV. In your Discovery Script these values could then be used like this:

## Set some global defaults
my $PRINT_LEVEL = 1; ## Set default verbosity of the output
my $THRESHHOLD = 1; ## Set some default threshhold
## Allow Argument override (values placed in the argument window, separate by a space.
$PRINT_LEVEL = shift @ARGV if $#ARGV >= 0;        ## verbosity level
$THRESHHOLD = shift @ARGV if $#ARGV >= 0;         ## Set some threshhold

Script of the Month

Analyze Potential Binding Sites. This script finds potential binding sites and returns some information about each.
It also makes use of perl subroutines, which is a very good way to add clarity to your programs. Note, that in DS 2.1 the name of an "object" is accessed using $object->Name; whereas in DS 2.0 it was accessed using $object->Label;

##PURPOSE: Find all binding cavities and report details of the cavity
## this works on the current molecule (tested for 1avd and 9hvp)
## REQUIRES: DS 2.1

use strict;
use MdmDiscoveryScript;
use DSCommands;

## Set global Defaults
my $MINUMUM_CHAIN_SIZE = 5;
##(one way to prevents a small protein "ligand" from being analyzed)

#________________________
sub ProteinChain ($$$)
{
my ($document, $aminoAcidChains,$string) = @_;
foreach my $chain (@$aminoAcidChains)
{
   my $numres = $chain->AminoAcids->Count;
   my $chainName = $chain->Name;
   print $string."length of chain $chainName = $numres\n";
   if ($numres >= $MINUMUM_CHAIN_SIZE)
   {
      $chain->Select()
   }else {
      print $string."chain $chainName excluded (too small)\n";
   }
}

$document->InvertSelection();
$document->DeleteObjects();
$document->DeselectAll();
$document->AddHydrogenAtoms;
#
return 0;
}
#___________________________________
sub Analyze_Sites ($$)
{
my ($sites,$string) = @_;
foreach my $site (@$sites)
{
   my $siteName = $site->Name;
   my $sitePoints = $site->BindingSitePoints;
   my $sp = $site->GetProperty("Point Count");
   my $vol = $site->GetProperty("Volume");
   print "${string}There are " . $sitePoints->Count ." points ($sp) in binding site $siteName, volume = $vol\n";
}
return 0;
}
#____________________________________

################
# MAIN PROGRAM
################
my $document = DiscoveryScript->LastActiveDocument(MdmModelType);
my $firstMolecule = $document->Molecules->[0];
my $moleculeName = $firstMolecule->Name;
my $aminoAcidChains = $firstMolecule->AminoAcidChains;
$document->DeselectAll();
print "Analyze Binding Sites for $moleculeName\n";

## Clean the protein. Leave only AA chains larger than a threshhold size
ProteinChain($document,$aminoAcidChains," ");
$document->SelectAll();

## Find binding sites from cavities
$document->CreateBindingSitesFromCavities( $firstMolecule);

# Get the binding sites
my $sites = $document->BindingSites;
print " There were " . $sites->Count . " cavities found.\n";

# Scan all Binding Sites and print data:
Analyze_Sites($sites," -> ");

The expected output for 9hvp is:

Analyze Binding Sites for 9hvp
length of chain A = 99
length of chain B = 99
length of chain I = 2
chain I excluded (too small)
There were 4 cavities found.
-> There are 2401 points (2401) in binding site Site 1, volume = 300.125000
-> There are 123 points (123) in binding site Site 2, volume = 15.375000
-> There are 107 points (107) in binding site Site 3, volume = 13.375000
-> There are 102 points (102) in binding site Site 4, volume = 12.750000