QikProp User Manual - gohom.win

1 Schr dinger PressQikProp user ManualQikProp user ManualQikProp user Manual Copyright 2012 Schr dinger, LLC. All rights reserved. While care has been taken in the preparation of this publication, Schr dinger assumes no responsibility for errors or omissions, or for damages resulting from the use of the information contained , Canvas, CombiGlide, ConfGen, Epik, Glide, Impact, Jaguar, Liaison, LigPrep, Maestro, Phase, Prime, PrimeX, QikProp , QikFit, QikSim, QSite, SiteMap, Strike, and WaterMap are trademarks of Schr dinger, LLC. Schr dinger and MacroModel are registered trademarks of Schr dinger, LLC. MCPRO is a trademark of William L.

2 Jorgensen. DESMOND is a trademark of D. E. Shaw Research, LLC. Desmond is used with the permission of D. E. Shaw Research. All rights reserved. This publication may contain the trademarks of other dinger software includes software and libraries provided by third parties. For details of the copyrights, and terms and conditions associated with such included third party software, see the Legal Notices, or use your browser to open $SCHRODINGER/docs/ (Linux and Mac OS) or %SCHRODINGER%\docs\html\ (Windows OS).This publication may refer to other third party software not included in or with Schr dinger software ("such other third party software"), and provide links to third party Web sites ("linked sites").

3 References to such other third party software or linked sites do not constitute an endorsement by Schr dinger, LLC or its affiliates. Use of such other third party software and linked sites may be subject to third party license agreements and fees. Schr dinger, LLC and its affiliates have no responsibility or liability, directly or indirectly, for such other third party software and linked sites, or for damage resulting from the use thereof. Any warranties that we make regarding Schr dinger products and services do not apply to such other third party software or linked sites, or to the interaction between, or interoperability of, Schr dinger products and services and such other third party A, September 2012 QikProp user ManualiiiContentsDocument vChapter 1: QikProp Citing QikProp in 6 Chapter 2: QikProp Preparing for the Importing Running QikProp in Normal Processing Running QikProp in Fast Processing Sorting Project Table 11 Chapter 3.

4 Running QikProp Running QikProp From Setting QikProp Options .. Setting Job Fixing Noncompliant Structures .. Running QikProp From the Command Monitoring QikProp QikProp Output Customizing QikProp with the QPlimits QikProp Use of Improvement of logS and Retrieval of the Most Similar Molecules .. 23 ContentsSchr dinger Suite 2012 Update 2ivChapter 4: Quality of QikProp Test Set Accuracy Conformation Dependence of Data 32 Appendix A: Descriptor 41 QikProp user ManualvDocument ConventionsIn addition to the use of italics for names of documents, the font conventions that are used inthis document are summarized in the table to other locations in the current document or to other PDF documents are colored likethis: Document descriptions of command syntax, the following UNIX conventions are used.

5 Braces {}enclose a choice of required items, square brackets [ ] enclose optional items, and the barsymbol | separates items in a list from which one item must be chosen. Lines of commandsyntax that wrap should be interpreted as a single name, path, and environment variable syntax is generally given with the UNIX conven-tions. To obtain the Windows conventions, replace the forward slash / with the backslash \ inpath or directory names, and replace the $ at the beginning of an environment variable with a %at each end. For example, $SCHRODINGER/maestro becomes %SCHRODINGER%\ references are given in the Windows convention by default, with Mac equivalents inparentheses, for example CTRL+H ( H).

6 Where Mac equivalents are not given, COMMAND should be read in place of CTRL. The convention CTRL-H is not used. In this document, to type text means to type the required text in the specified location, and toenter text means to type the required text, then press the ENTER to literature sources are given in square brackets, like this: [10]. FontExampleUseSans serifProject TableNames of GUI features, such as panels, menus, menu items, buttons, and labelsMonospace$SCHRODINGER/maestro File names, directory names, commands, envi-ronment variables, command input and outputItalicfilename Text that the user must replace with a valueSans serif uppercaseCTRL+H Keyboard keysSchr dinger Suite 2012 Update 2viChapter 1 QikProp user Manual1 QikProp user ManualChapter 1 OverviewQikProp is a quick, accurate, easy-to-use absorption.

7 Distribution, metabolism, and excretion(ADME) prediction program designed by Professor William L. Jorgensen. QikProp predictsphysically significant descriptors and pharmaceutically relevant properties of organic mole-cules, either individually or in addition to predicting molecular properties, QikProp provides ranges for comparing a partic-ular molecule s properties with those of 95% of known drugs. QikProp also flags 30 types ofreactive functional groups that may cause false positives in high-throughput screening (HTS)assays. The range of values that cause a molecule to be flagged as dissimilar to other knowndrugs can be modified in the QPlimits file see Section on page 20 for can be run either from the Maestro GUI or from the command line.

8 QikProp has twomodes: normal mode, and fast mode. In fast mode, certain time-consuming calculations areomitted, some properties are not predicted, and some have different values. For more informa-tion, see Chapter properties and descriptors can be used as input to Strike, which is a collection ofchemically-aware statistical tools for examining correlations within data. It can develop andemploy QSAR/QSPR models using partial least squares, principal component analysis, andmultiple linear regression; generate univariate and bivariate statistics; and perform similarity/diversity analysis in descriptor and 2D-structure space.

9 Strike can be run from Maestro. Forfurther information about Strike, see the Strike user Manual or contact your Schr dinger each successfully processed molecule, QikProp produces the following descriptors andproperties. Those that are not predicted in fast mode are marked with a dagger ( ). Thosewhose values differ between fast and normal mode are marked with a double dagger ( ).Chapter 1: IntroductionSchr dinger Suite 2012 Update 2 2 Table QikProp properties and or DescriptorDescriptionRangea or recommended valuesmolecule nameMolecule name taken from the title line in the input structure file.

10 If the title line is blank, the input file name is used.#starsNumber of property or descriptor values that fall outside the 95% range of similar values for known drugs. Outlying descriptors and predicted properties are denoted with asterisks (*) in the .out file. A large number of stars suggests that a molecule is less drug-like than molecules with few stars. The following properties and descriptors are included in the deter-mination of #stars: MW, dipole, IP, EA, SASA, FOSA, FISA, PISA, WPSA, PSA, volume, #rotor, donorHB, accptHB, glob, QPpolrz, QPlogPC16, QPlogPoct, QPlogPw, QPlogPo/w, logS, QPLogKhsa, QPlogBB, #metabol0 5#amineNumber of non-conjugated amine 1#amidineNumber of amidine and guanidine #acidNumber of carboxylic acid 1#amideNumber of non-conjugated amide 1#rotorNumber of non-trivial (not CX3), non-hindered (not alkene, amide, small ring) rotatable 15#rtvFGNumber of reactive functional groups.