QSAR - How To Use This Book

QSAR

How To Use This Book

Cerius² QSAR+ is a complete guide to Cerius^2TM modules that are part of the Drug Discovery Workbench^TM (DDW^TM):

C²·QSAR+, a data exploration and productivity tool for investigating quantitative structure-activity relationships.
C²·MFA (molecular field analysis), providing a method for quantifying the interaction energy between a probe molecule and a set of aligned target molecules in a QSAR.
C²·GFA (genetic function approximation), offering a new approach to the challenge of building quantitative structure-activity relationship (QSAR) and quantitative structure-property (QSPR) models.
C²·CSAR (classification structure-activity relationship) is a tool for the fast derivation of partitioning models for the prediction of activities or properties.

Because these modules are part of the Cerius² product line, you perform some DDW tasks using functionality located in other Cerius² modules. Detailed descriptions of these tasks are provided in other Cerius² books and are cross-referenced throughout this book. (See Using other Cerius² books on page xix.)

This book contains the following chapters:

Introduction to the Cerius² Drug Discovery Workbench, which shows you an overview of the modules used for drug discovery work and how they relate to QSAR+.
QSAR+ QuickStart, a simple tutorial that demonstrates the basic functionality of QSAR+. To run the tutorial, you must have QSAR+ installed.
Theory: Statistical Methods describes the data analysis, regression, and validation methods used in the QSAR+ module.
Theory: QSAR+ Descriptors describes the categories of descriptors available for your use in QSAR+.
Working with the Study Table describes the layout and functioning of the study table, a version of a standard Cerius² table that is used to store and manage the information about descriptors, molecules, and QSARs.
Working with Molecules describes how you manage molecules within QSAR+, including loading the molecules into a study table, the processing options that are available for automatic processing of the molecules, and how to use MDL SD files with the study table.
Working with Descriptors explains what QSAR+ descriptor sets are and how to use them. It also discusses managing descriptors, editing a descriptor database, and how to use the receptor surface analysis descriptor.
Working with Fragment Constants describes the steps you follow to use fragment constants to relate the effect of substituents on a "reaction center" from one type of process to another. These steps include selecting fragment constants, searching for core substructures, and editing the fragment constants database.
Performing Molecular Field Analysis explains the steps you take to quantify the interaction energy between a probe molecule and a set of aligned target molecules in a QSAR.
Performing Molecular Shape Analysis explains how QSAR+ incorporates conformational flexibility and shape data to generate a 3D QSAR.
Working with Variables and Observations defines variables and observations in QSAR+ and the study table and explains how to identify and select variables and observations when generating a QSAR.
Working with Statistics explains how to select your statistical method and how to view and validate the results of your selected statistical analysis.
Genetic Function Approximation explains how to use the genetic function approximation instead of regression analysis to generate candidate models.
Using the Equation Viewer explains how to use the QSAR+ equation viewer to select, load, add, delete, plot, and save QSAR equations.
Classification Structure-Activity Relationship (CSAR) documents the methodology and interface of the C²·CSAR product, including a tutorial.
The References appendix lists the papers and other publications that are cited in this book and others on which QSAR is based.
Tutorials covering an array of QSAR functionality are provided as appendixes at the end of this documentation set.

Preparing to work

To use the software as described in this book, you should be familiar with:

The Cerius2·Visualizer and graphical user interface.
Basic Cerius2 facilities for model manipulation.

You need the following resources to use the DDW software described in this book:

A licensed copy of Cerius2.
A licensed copy of QSAR+. You may also want to have one or more of the C²·MFA, C²·GFA, C²·Descriptors+, or C²·CSAR modules. The C²·Analog Builder is required if you want to work with fragment constants.
A home directory in which you can create subdirectories.

How to find information


If you want to know about...	Read...
The Cerius² Drug Discovery Workbench (DDW)	Chapter 1, Introduction to Cerius² Activity Prediction
Performing basic QSAR+ operations	Chapter 2, QSAR+ QuickStart Chapter 5, Working with the Study Table Chapter 6, Working with Molecules Chapter 7, Working with Descriptors Chapter 11, Working with Variables and Observations Chapter 12, Working with Statistics Chapter 14, Using the Equation Viewer
Performing a molecular shape analysis	Chapter 10, Performing Molecular Shape Analysis
Performing a molecular field analysis	Chapter 9, Performing Molecular Field Analysis
Using the genetic function approximation (GFA) algorithm	Chapter 13, Genetic Function Approximation
Using the genetic partial least squares algorithm	Chapter 13, Genetic Function Approximation
An overview of QSAR analysis	Chapter 2, QSAR+ QuickStart Chapter 3, Theory: Statistical Methods Chapter 5, Working with the Study Table Publications listed in References appendix
The descriptors used in QSAR+	Chapter 4, Theory: QSAR+ Descriptors Chapter 7, Working with Descriptors Chapter 8, Working with Fragment Constants Chapter 9, Performing Molecular Field Analysis Chapter 10, Performing Molecular Shape Analysis
Calculating fragment constants	Chapter 4, Theory: QSAR+ Descriptors Chapter 8, Working with Fragment Constants
QSAR statistical methods	Chapter 12, Working with Statistics Chapter 13, Genetic Function Approximation Chapter 3, Theory: Statistical Methods

Using other Cerius2 books

You can find additional information about Cerius² and its activity prediction modules in several other books:

Cerius² Hypothesis and Receptor Models -- Part One, Alignment, describes tools used to superimpose molecules to satisfy various alignment conditions. These tools permit alignment of molecules using least square fitting with atom equivalencies specified either by automatic atom matching algorithms or by manual atom matching. Part Two, Receptor Modeling, describes the 3D visual environment that the application provides for receptor hypothesis exploration. It provides information on how to generate pseudo-receptors from the overlay of active compounds and how to use pseudo-receptors to evaluate new, potentially active compounds. Part Three, Pharmacophore, describes the pharmacophoric hypotheses that are generated through the interfaces to Catalyst ConFirm, HipHop, and Hypo. It includes information on how to use the interfaces to generate conformers, align structures by common chemical features, generate hypotheses, and use aligned structures to generate receptor surfaces in Receptor. Part Four, Database Query, describes how to use Catalyst/Info, CatShape, and ISIS to construct queries to search databases and to retrieve, examine, and save structures from the databases that fit your criteria.
Cerius² Diversity -- Describes the C²·Diversity module, which analyzes chemical diversity to design and evaluate compound libraries and reagent sets for combinatorial chemistry.
Cerius² Modeling Environment --Describes the integrated set of tools for session management and atomistic modeling that form the core of the Cerius2 modeling environment.
Cerius² Builders -- Discusses the specialized builder modules (that is, the Analog Builder, Crystal Builder, Surface Builder, Interface Builder, Polymer Builder, and Amorphous Builder modules) that can be added to supplement the basic model sketching capabilities provided by the Cerius2 modeling environment.
Cerius² Simulation Tools -- Discusses the Open Force Field, Force Field Editor, Charges, Minimizer, Dynamics Simulation and Analysis.
Cerius2 Conformational Search and Analysis -- Discusses Conformer Search, Conformer Analysis, and Field Calculation.
Cerius² Using Command Scripts -- Shows how to capture and replay a script of Cerius² commands, and how to enhance your command scripts with the features of the Tool Command Language (Tcl).
Cerius2 Installation and Administration Guide -- Provides step-by-step instructions for installing and administering Cerius² in your operating environment.

Typographical conventions

Unless otherwise noted in the text, the is book uses these typographical conventions:

Words in italic represent variables. For example:

Pred_dependent_variable

: In this example, the name of an appropriate dependent variable replaces the value dependent_variable. (For example, if the name of the dependent variable were "Activity", QSAR+ would display a value of Pred_Activity.)

Names of most items that appear in the Cerius² interface are presented in bold type. For example:

Access the QSAR card deck, then choose View Equations from the Equation Viewer menu card.
Items that you type are presented in bold type. For example:

To name your file, enter testset.qsar in the text entry box.
Excerpts of input/output files appear in typewriter font. For example:


Surface		Coordinates
point		X    Y    Z			mol atom		charge