FirstDiscovery 3.0 Quick Start Guide Copyright © 2004 Schrödinger, LLC. All rights reserved. Schrödinger, FirstDiscovery, Glide, Impact, Jaguar, Liaison, LigPrep, Maestro, Prime, QSite, and QikProp are trademarks of Schrödinger, LLC. MacroModel is a registered trademark of Schrödinger, LLC. To the maximum extent permitted by applicable law, this publication is provided “as is” without warranty of any kind. This publication may contain trademarks of other companies. Revision A, June 2004 Contents Chapter 1: Document Overview..........................................................................1 Chapter 2: The FirstDiscovery Suite ..................................................................3 Chapter 3: Introduction to Maestro ...................................................................5 3.1 General Interface Behavior ..................................................................................5 3.2 Starting Maestro...................................................................................................5 3.3 The Maestro Main Window .................................................................................6 3.3.1 The Menu Bar ..........................................................................................7 3.3.2 The Toolbar ..............................................................................................8 3.3.3 Mouse Functions in the Workspace .......................................................11 3.3.4 Shortcut Key Combinations ...................................................................11 3.4 Maestro Projects ................................................................................................12 3.4.1 The Project Table Toolbar ......................................................................13 3.4.2 The Project Table Menus........................................................................15 3.4.3 Selecting Entries.....................................................................................15 3.4.4 Including Entries in the Workspace .......................................................16 3.4.5 Mouse Functions in the Project Table ....................................................16 3.4.6 Project Table Shortcut Keys ...................................................................17 3.5 Building a Structure...........................................................................................18 3.6 Selecting Atoms.................................................................................................21 3.7 Maestro Command Scripts.................................................................................22 3.8 Specifying a Maestro Working Directory..........................................................23 3.9 Undoing an Operation........................................................................................24 3.10 Running and Monitoring Jobs..........................................................................24 3.11 Getting Help.....................................................................................................26 3.12 Ending a Maestro Session................................................................................26 Chapter 4: Protein Preparation ........................................................................27 4.1 Preparing Proteins for FirstDiscovery ...............................................................27 4.2 Importing the Protein Complex Structure..........................................................27 4.3 Deleting Unwanted Waters ................................................................................28 4.4 Adjusting the Ligand .........................................................................................29 4.5 Running Protein Preparation on the Structure ...................................................32 4.6 Protein Preparation Output Structures ...............................................................34 FirstDiscovery 3.0 Quick Start Guide iii Contents Chapter 5: Introduction to Glide ......................................................................35 Chapter 6: Creating Glide Grid Files ...............................................................37 6.1 Creating a Working Directory............................................................................37 6.2 Preparation .........................................................................................................38 6.3 Importing Maestro Files.....................................................................................38 6.4 Saving a Scratch Project ....................................................................................40 6.5 The Glide Panel: Choosing and Naming a Grid Generation Job.......................41 6.6 Designating the Ligand Molecule......................................................................43 6.7 Defining the Enclosing Box Center ...................................................................44 6.8 Starting and Monitoring the Grid Calculation ...................................................45 6.9 Exercise Summary .............................................................................................47 6.10 Running the Job With a Command Script .......................................................47 Chapter 7: Docking.............................................................................................49 7.1 Preparation .........................................................................................................49 7.2 Specifying a Pre-Existing Grid File for Docking ..............................................50 7.3 Selecting Ligands for Docking ..........................................................................50 7.4 Specifying a Reference Ligand..........................................................................53 7.5 Reviewing Options for Scoring and Output.......................................................54 7.6 Glide Constraints and Similarity........................................................................56 7.7 Starting the Docking Job....................................................................................58 7.8 Exercise Summary .............................................................................................58 7.9 Running the Job With a Command Script .........................................................59 Chapter 8: Examining Glide Data.....................................................................61 8.1 Preparation .........................................................................................................61 8.2 Displaying Pose Data.........................................................................................62 8.3 Viewing Poses....................................................................................................62 8.4 Coloring and Labeling the Ligand .....................................................................64 8.5 Displaying Atoms by Proximity ........................................................................65 8.6 Coloring Carbons by Molecule Number............................................................66 8.7 Changing Molecular Representations................................................................66 8.8 Visualizing Bad and Ugly Contacts ...................................................................66 8.9 Displaying Hydrogen Bonds..............................................................................68 8.10 Writing a File Containing a Single Ligand......................................................69 iv FirstDiscovery 3.0 Quick Start Guide Contents 8.11 Saving Multiple Ligand Poses to a Single File................................................70 8.12 Exercise Summary ...........................................................................................70 Chapter 9: Introduction to Liaison...................................................................71 Chapter 10: Liaison Simulations.......................................................................73 10.1 Preparation .......................................................................................................73 10.2 Specifying Job Settings....................................................................................74 10.3 Loading a Receptor..........................................................................................75 10.4 Creating a Ligand Source File .........................................................................76 10.5 Specifying a Ligand Source File and File Format ...........................................77 10.6 Setting Job Parameters.....................................................................................78 10.7 Specifying Atoms to Freeze.............................................................................79 10.8 Starting the Liaison Job ...................................................................................81 10.9 Exercise Summary ...........................................................................................82 10.10 Running the Job With a Command Script .....................................................84 Chapter 11: Analyzing Liaison Data ................................................................85 11.1 Preparation .......................................................................................................85 11.2 Creating a Binding Energy File .......................................................................86 11.3 Fitting