FirstDiscovery Command Reference Manual Impact: Integrated Modeling Program using Applied Chemical Theory Version 3.0, June 2004 For inquiries about FirstDiscovery TM and Impact TM contact: Schr¨odinger 1500 SW First Avenue, Suite 1180 Portland, OR 97201–5881 503–299–1150 503–299–4532 fax Email: [email protected] Copyright c 2004 Schr¨odinger, LLC. All rights reserved. Schr¨odinger, FirstDiscovery, Glide, Impact, Jaguar, Liaison, Maestro, and QSite are trademarks of Schr¨odinger, LLC. MacroModel is a registered trade- mark of Schr¨odinger, 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. FirstDiscovery Version 30511 June 2004 Chapter 1: Introduction to FirstDiscovery 1 Introduction to FirstDiscovery ImpactTM (Integrated Modeling Program using Applied Chemical Theory), the heart of Schr¨odinger’s FirstDiscoveryTM modeling suite, is an integrated program for molecular mechanics simulations. It allows the user to define the simulation system (usually a protein or DNA molecule in aqueous solution) and to perform Monte Carlo or molecular dynamics simulations. In addition, the user has at her/his disposal a whole array of tools for analyzing the results of the simulations. Finally, Impact is the “driver” for the high-throughput ligand screening program GlideTM, the LiaisonTM module for calculating ligand binding energies, and the mixed mode Quantum Mechanics/Molecular Mechanics program QSiteTM. This is the FirstDiscovery Command Reference Manual. It documents using Impact from the command-line, and all the keywords of Impact input files. Running FirstDiscovery from Maestro, and discussion of the principal appli- cations Glide, Liaison, and QSite, are more fully documented in the other FirstDiscovery manuals: • FirstDiscovery Quick Start Guide A collection of tutorial examples that illustrate Glide, Liaison and QSite. • FirstDiscovery User Manual A presentation of FirstDiscovery especially focussed on its Maestro in- terface. • FirstDiscovery Technical Notes A collection of case studies elaborating on the scientific methods and results of Glide, Liaison, and QSite. 1.1 A Brief History of Impact The current commercial FirstDiscovery suite was developed from the aca- demic Impact originally designed in the laboratory of Professor Ronald M. Levy at Rutgers University. The following people have contributed to the development of FirstDiscovery and Impact: 1.1.1 Commercial Versions • v3.0 (June 2004) Jay Banks, Yixiang Cao, Wolfgang Damm, Richard Friesner, Emilio Gallicchio, Thomas Halgren, Ronald Levy, Daniel Mainz, Rob Murphy, and Matt Repasky. • v2.7 (October 2003) Jay Banks, Yixiang Cao, Wolfgang Damm, Richard Friesner, Emilio Gallicchio, Thomas Halgren, Ronald Levy, Daniel Mainz, Rob Murphy, and Matt Repasky. FirstDiscovery 3.0 Command Reference Manual 1 Chapter 1: Introduction to FirstDiscovery • v2.5 (January 2003) Jay Banks, Yixiang Cao, Wolfgang Damm, Richard Friesner, Emilio Gallicchio, Thomas Halgren, Ronald Levy, Daniel Mainz, and Rob Murphy. • v2.0 (June 2002). Jay Banks, Yixiang Cao, Wolfgang Damm, Richard Friesner, Emilio Gallicchio, Thomas Halgren, Ronald Levy, Daniel Mainz, and Rob Murphy. • v1.8 (September 2001). Jay Banks, Yixiang Cao, Wolfgang Damm, Richard Friesner, Emilio Gallicchio, Thomas Halgren, Ronald Levy, Daniel Mainz, and Rob Murphy. • v1.7 (March 2001). Jay Banks, Yixiang Cao, Richard Friesner, Emilio Gallicchio, Thomas Halgren, Ronald Levy, Daniel Mainz, Rob Murphy, and Ruhong Zhou. • v1.6 (November 2000). Jay Banks, Michael Beachy, Yixiang Cao, Richard Friesner, Emilio Gallicchio, Ronald Levy, Daniel Mainz, Rob Murphy, and Ruhong Zhou. • v1.0 (June 1999). Jay Banks, Richard Friesner, Emilio Gallicchio, Avi- jit Ghosh, Ronald Levy, Rob Murphy, Anders Wallqvist, and Ruhong Zhou. • v0.95 (Nov 1998). Jay Banks, Richard Friesner, Emilio Gallicchio, Avi- jit Ghosh, Ronald Levy, Rob Murphy, Anders Wallqvist, and Ruhong Zhou. • v0.9 (Aug 1998). Jay Banks, Mark Friedrichs, Richard Friesner, Emilio Gallicchio, Avijit Ghosh, Ronald Levy, Rob Murphy, Anders Wallqvist, and Ruhong Zhou. • v0.8 (May 1998). Jay Banks, Chris Cortis, Shlomit Edinger, Mark Friedrichs, Richard Friesner, Emilio Gallicchio, Avijit Ghosh, Ronald Levy, Rob Murphy, Anders Wallqvist, and Ruhong Zhou. 1.1.2 Academic Versions • V7.0 (August 1996). Jay Banks, Yanbo Ding, Gabriela Del Buono, Francisco Figueirido, Ronald Levy, and Ruhong Zhou. • V6.0 (January 1994). Les Clowney, Francisco Figueirido, Ronald Levy, Lynne Reed, Maureen Smith-Brown, Asif Suri and John Westbrook. • V5.8 (December 10, 1991). Les Clowney, Francisco Figueirido, Douglas Kitchen, Ronald Levy, Maureen Smith, Asif Suri and John Westbrook. • V5.7 (December 17, 1990). Steve Back, Teresa Head-Gordon, Douglas Kitchen, Dorothy Kominos, Ronald Levy and John Westbrook. • V5.5 and earlier (June 1990). Steve Back, Donna Bassolino, John Blair, Fumio Hirata, Douglas Kitchen, David Kofke, Dorothy Kominos, Ronald Levy, Asif Suri and John Westbrook. 2 FirstDiscovery 3.0 Command Reference Manual Chapter 1: Introduction to FirstDiscovery 1.2 Major Features The major features of Impact include: • Build Protein/DNA/RNA from Residue Sequences • Energy Minimization • Molecular Dynamics • Monte Carlo Methods • Fast Multipole Method (FMM) • Multiple Time-step Algorithm r-RESPA • S-Walking/J-Walking Methods • Explicit Solvation Model • Poisson-Boltzmann Continuum Solvation (pbf) • Surface Generalized Born Solvation Model (sgb) • OPLS-AA with Automatic Atomtype Recognition • Flexible Schemes for Freezing Part of System • QSite: Mixed-Mode QM/MM Simulations for Reactive Chemistry • Liaison: Calculating and Predicting Ligand Binding Energies • Glide: High-Throughput Ligand-Receptor Docking 1.3 Hardware Requirements Schr¨odinger tests and distributes FirstDiscovery 3.0 for SGI IRIX, IBM AIX, and Intel-x86 compatible Linux-based machines at this time. For current information on other platforms, please contact Schr¨odinger. 1.4 Installation To install FirstDiscovery please see the Schr¨odinger Installation Guide.A printed version of this manual and other documentation should come with your CD-ROM. PostScript, PDF, and HTML version for most of the First- Discovery manuals should be on the CD-ROM itself. For those that want to cut to the chase, installation is often as easy as running: % /bin/sh INSTALL from the CD-ROM, and following the prompts. But please see the Installa- tion Guide. After installation, in the directory specified by your $SCHRODINGER environ- ment variable, there should be an Impact directory labelled with the current version number, at this printing, this is ‘impact-v30511’. In that directory, there are seven subdirectories: FirstDiscovery 3.0 Command Reference Manual 3 Chapter 1: Introduction to FirstDiscovery bin/ The executable binary and scripts for running all manner of Impact-based jobs. Since these are platform-dependent, these files are separated into further subdirectories with their plat- form’s designation, e.g. Linux-x86/. data/ The database parameters for the opls, opls2000, and amber force fields. docs/ Electronic versions of the FirstDiscovery Reference Manual (this document) are located here. lib/ Platform-dependent shared libraries needed by Impact are kept here. disabled_lib/ Disabled shared libraries, moved from the ‘lib/’ subdirectory should be kept here. Disabling libraries should only be done within Schr¨odinger’s recommendations. samples/ The example files noted in this manual’s appendices. tutorial/ Files that correspond to the instructional material in the First- Discovery Quick Start Guide that walks you through various types of FirstDiscovery calculations. A file ‘compatibility’ is also in your ‘impact-v30511’ directory, listing the minimum version numbers of other Schr¨odinger products compatible with this FirstDiscovery release. All Schr¨odinger startup scripts will use this information automatically. The single important environment variable each Impact user has to have is $SCHRODINGER. It should be set to your top-level installation directory for Schr¨odinger products, e.g. /usr/local/bin/schrodinger. If you plan on using some of the utility scripts from a command-line interface, you might like to add the directory $SCHRODINGER/utilities to your PATH enviroment variable, so that the scripts in this directory are accessible by name without the full directory name prepended. If your command-line shell is sh, ksh, or bash, this is done by: (sh/ksh/bash)% export PATH=$PATH:$SCHRODINGER/utilities and if your shell is csh or tcsh, then do: (csh/tcsh)% setenv PATH $PATH:$SCHRODINGER/utilities To run a FirstDiscovery example, first make sure that $SCHRODINGER is set to your Schr¨odinger installation directory. Then cd to one of example directory and type: % $SCHRODINGER/impact -i input file -o log file This will read from the input file and write the log file to log file. If -o is not specified, Impact will set the log file name to be the same as your input file, but with a .log extension in place of .inp. 4 FirstDiscovery 3.0 Command Reference Manual Chapter 1: Introduction to FirstDiscovery Note that the log file (stdout) is not the file specified in the top write command in the input file, which is usually more detailed than the log file. Just typing impact with no arguments is equivalent to typing main1m: the program then looks for an input file named ‘fort.1’, and writes to standard output. If an input file is specified but a log file is not, Impact