Tips and Tricks using Discovery Studio

Transcription

1 Tips and Tricks using Discovery Studio Allister J. Maynard, Ph.D. Senior Manager, R&D July 31 st, 2008

2 New Science and Customized Workflows for Drug Discovery Research Webinar Series June 12, Advances in Protein Modeling and Protein-Protein Interactions in Discovery Studio June 19, Physics-Based Protein Ionization and pk Estimation June 26, Towards Increased Accuracy in Computational Drug Discovery with QM/MM July 10, Pharmacophore Guided Fragment-Based Drug Design July 17, Advances in Pharmacophore Modeling and Parallel Screening July 24, Workflow Customization with DS Developer Client July 31, Tips and Tricks using Discovery Studio Recordings Available: Accelrys, Inc. 2

3 Tips and Tricks using Discovery Studio - Agenda Discovery Studio Client Overview Introduction to the User Interface 3D Window Sequence Window Chart Windows Shortcuts Scripting in Discovery Studio Script Window Running a script Customizing Discovery Studio Scripting Examples Discovery Studio Forums 2008 Accelrys, Inc. 3

4 Discovery Studio Linux and Windows! Pipeline Pilot DS Developer Client Discovery Studio Client Web Client SciTegic Server Protocol CHARMm Protocol MODELER Protocol BLAST Protocol LigandFit Protocol Catalyst 2008 Accelrys, Inc. 4

5 Discovery Studio Client Overview Free Downloads Discovery Studio Visualizer light version High-quality visualization of Molecules, Sequences and more Work with table data, hierarchy and 3D together Create and run scripts Discovery Studio ActiveX Control embed in PowerPoint, Internet Explorer etc. Same level of 3D Visualization in an embedded container Use in interactive web pages, PowerPoint or Pipeline Pilot reports FREE DOWNLOAD!! Accelrys, Inc. 5

6 Discovery Studio Client Discovery Studio Client All functionality from Discovery Studio Visualizer Charts Point, Line, 3D, Hit Rate, Heat Map, Histogram, Ramachandran, Contact Tools Explorer Binding Site Protein/Nucleic acid builder Evolutionary Trace/Phylogenetics Much more! Scientific Protocols Access a variety of scientific workflows Run out-of-the-box science Run customized protocols 2008 Accelrys, Inc. 6

7 Discovery Studio Client Overview 2008 Accelrys, Inc. 7

8 Introduction to the User Interface 3D Window Supported File Formats: Standard Protein Data Bank (PDB) Crystallographic Information (CIF includes x-ray data) Comma Separated Values (CSV) Cambridge Structure Data (CSD) XYZ coordinate (XYZ) Native format (.MSV) stores display options, etc. Legacy Applications Catalyst (CPD, CHM) InsightII (GRD, PSV, CAR) Quanta (MBK, MSF) Cerius2 (MSI) CNX (MAP) CHARMm (CRD, PSF) 3 rd Party MDL (SD, SKC) Daylight (SMI) Sybyl (MOL2) 3D & Image Povray (POV) VRML World (WRL) Image (PNG,JPEG,BMP) Over 25 Free Download Formats 2008 Accelrys, Inc. 8

9 Introduction to the User Interface 3D Window Molecules, Chains, Residues, Atoms, Bond Surfaces, Isosurfaces, Labels, Slicing Planes, Transformation matrices, Points Binding Sites, Spheres, Selections (Groups) Monitors: Distance, Angle, Torsion, Plane, Normal, H-Bond, Bump, Violations, Centroid, Chirality, Dipole Moment, Neighbors, Tethers, Valence X-ray: Cells, Electron Density, 3D Pointers, Alternate Conformers, Space Groups, Symmetry Operators Pharmacophore: Query Atoms/Bonds, Features, Custom Features, Shapes, Excluded Volumes Simulation: Forcefield Types, Distance, Angle, Torsion, Fixed atom restraints 2008 Accelrys, Inc. 9

10 Introduction to the User Interface Demo 3D Window Opening a file from a URL Selecting, Rotating, Translating, Zoom Understanding the Hierarchy View Exploring the Data Table Sequence Window Creating from a molecule Annotations Interactivity Chart Windows Ramachandran 3D Plot Interactivity Customization Menus Tools Toolbars 2008 Accelrys, Inc. 10

11 Shortcuts Ctrl-1 F11 Ctrl-T Ctrl-H F1 Ctrl-C Ctrl-V Maximize screen (Hide/Show tools) Toggle Full-screen mode Show Data Table Show Hierarchy View Context-sensitive Help Copy Excel, Word, PowerPoint etc. Paste MDLDraw, Chemdraw All documented 2008 Accelrys, Inc. 11

12 Paste Demo Pasting an image from Discovery Studio 2008 Accelrys, Inc. 12

13 ActiveX Demo Creating impressive interactive 3D slides Download free of charge: Accelrys, Inc. 13

14 Scripting in Discovery Studio What if You do the same thing repeatedly? You want to link some steps together? You want a button/icon that does something, that you can t normally do? Scripting! Automate repetitive tasks Link several tasks or calculations together in sequence See also previous webinar: DS Developer Client Explore calculations that are not available from any of the application's modules DS Scripting is not just for automation Write your own new science! Integrate with other software Call any Perl module Run a program Access a web service 2008 Accelrys, Inc. 14

15 Scripting in Discovery Studio Perl Fully documented with context sensitive help (in DS) Object Orientated easier to understand Scripting is done on the Document (Data Model) Molecular Data Model 3D Window, Hierarchy View, Data Table Sequence Data Model Sequence window/sequence annotation window Forcefield Data Model Typing Protocol Running a protocol Scripts can be run Interactively from Discovery Studio Using command-line Perl From within a protocol Do what YOU want! 2008 Accelrys, Inc. 15

16 Scripting - DSVisualizer 2008 Accelrys, Inc. 16

17 Script or Protocol? If I want to create a custom piece of functionality when do I use Pipeline Pilot and when do I use DiscoveryScript? The DiscoveryScript language primarily provides access to the Client-side functionality in Discovery Studio Pipeline Pilot and it s DS protocols primarily access Server-side functionality (i.e. Modeler, CHARMm, LigandFit etc.) However Protocols can be launched from a DiscoveryScript and a DiscoveryScript can be embedded into a component in a protocol Therefore, any solution can be delivered as a script or a protocol 2008 Accelrys, Inc. 17

18 Creating Scripts - Script Window The Script Window is an Integrated Development Environment (IDE) Create and edit scripts Syntax Check Button Context sensitive help Error checking Script Run Button Script execution Script Editor View Script Output View 2008 Accelrys, Inc. 18

19 Running a Script Demo Opening a script Running a script Customizing Discovery Studio with Scripts Examples 2008 Accelrys, Inc. 19

20 Creating New Visualization Techniques using Scripting Critical Challenges Customer requested to highlight a user defined atomic property Vary both the Ball size and atom color according to the specified atomic property value DS Client already has ability to change atom color to correspond to an atomic property but not the ball radius of a ball and stick representation Image area Solution Powered by Discovery Studio Script acts on current window in GUI User can adjust color spectrum and ball radius range within the script Launching script from GUI modifies display in seconds Can be easily modified to work on any existing property i.e. Occupancy, Isotropic Displacement, Partial Charge Results Delivered DiscoveryScript color_scale_ballsize_by_property.pl Provides a non-standard display style option Purpose: Change the display style of the last active document so that the atoms are represented by ball and stick which are colored with a RedWhiteBlue spectrum whose values are associated with the 'Isotropic Displacement' property and the BallSize is proportional to the value of the 'Isotropic Displacement' Accelrys, Inc. 20

21 Identify Hydrophobic Cavities and Remove Waters from them using Scripting Critical Challenges Customer request: Automatically identify Hydrophobic cavities in a receptor Delete water molecules within specified threshold from the center of these cavities Image area Solution Powered by Discovery Studio Cavities: Uses CreateBindingSitesFromCavities function Hydrophobic: Sum the Hydrophobicity of the amino acid residues within 3 angstrom of each binding site. Cavities w/ sums > 1.0 are Hydrophobic Waters in Hydrophobic Cavities: all waters within 3 angstrom of a binding site object that is residing in a hydrophobic cavity are deleted 2007 Accelrys, Inc. Results Delivered DiscoveryScript remove_waters_hydrophob_cav.pl All these steps could be performed manually Script provides automation and links several tasks together In addition to removing waters: Defines groups for each hydrophobic cavity Colors atoms of cavities by their amino acid hydrophobicity 21

22 Running 3rd Party Software using DiscoveryScript and PipelinePilot Critical Challenges Customer requested example of running 3 rd party executable from a DiscoveryScript and a PP Protocol from the DS Client The executable: MUSTANG: A MUltiple STructural AligNment algorithm Image area Solution Powered by Discovery Studio User specifies input protein structures Input proteins are filtered for single chain proteins only Input file with path and pdb filenames generated Executable launched with appropriate flags Output structure and sequence files manipulated to be compatible with DS Client 2007 Accelrys, Inc. Results Delivered Illustrates integration with other software DiscoveryScript run_mustang.pl Custom Protocol Align Structures with Mustang 22

23 Become a member and take advantage! Customized Workflows and Scripts can be downloaded from Accelrys Community site: Accord Discovery Studio Materials Studio Pipeline Pilot Launch from DS client 2008 Accelrys, Inc. 23

24 Tips and Tricks using Discovery Studio Wrap Up Discovery Studio Client Overview Introduction to the User Interface 3D Window Sequence Window Chart Windows Shortcuts Scripting in Discovery Studio Script Window Running a script Customizing Discovery Studio Scripting Examples Discovery Studio Forums 2008 Accelrys, Inc. 24