schrodinger knime extensions

Jean-ChristopheMozziconacciandVolkerEyrichh#p://www.schrodinger.com/upload/KNIME_Overview.pdf

KNIMEdesktopandSchrödingerextensionsoverview

Schrödingerextensions•  150+nodes:

–  CoveringmostoftheSchrödingertoolsMostrecentaddiGons:Residuescanning,PrimeEnergy,SiteMap,PyMOL,GlidegridwriterManytakeinandoutputsdfandpdbormol2ontopofMaestroformatNewestnodesusethesameconfiguraGonpanelasMaestro(seetheResiduescanningnode)

–  StructureanddatamanipulaGonnodes(egSplitbystructure,deleteatoms)–  GUInodes(egRunMaestro,RunPyMOL)–  ScripGngnodes:RunMaestrocommand,Chemistryexternaltool,Pythonnodes–  UGlitynodes:Setupdiagnosisandworkflowlist

•  50+workflowexamples–  Workflowpage:descripGonsanddownloadtheonesofinterest–  WholesetcanbedownloadedwiththeSuite–  ManyotherworkflowdraXsavailableondemand

Schrödingerextensions•  TestedwithlatestKNIMEversionandincludetheversionavailableattheGmeof

therelease•  Parameterflowvariablecapability

–  UsetheopGonsnotexposedintheconfiguraGonpanels(egcommandlineonly)–  ImplementedforthemainnodesegGlide,MMod(egOPLS2.1),Jaguar

•  2Drenderer–  2DcoordinategeneraGonandrenderingThedefaultrenderercanbesetforMaestrocolumns

–  CanbeusedintheReportdesigner

Schrödingerextensions•  Moreandsimplifiedstart-upopGons andstand-aloneinstallaGonconfiguraGoninthePreferences

–  In$SCHRODINGER/knimestart-upscript–  eguseastand-aloneKNIMEinstallaGon,settemporarydirectories,thememorylimit…

•  KNIMEmenuinMaestro–  ConnecttoKNIMEmodetoexchangestructureswithaKNIMEsessionKNIME-Maestroconnectornode(Improvedin2015-1:automaGcconnecGon/close,moremodes)

–  Build,import,editandrunworkflowsfromMaestroonprojecttabledataDynamicallygeneratedGUItoaltersomeparameters.

•  SimplifiedbatchexecuGon:KNIME_batch.py–  BatchcommandgeneraGonbasedonworkflowannotaGonsStand-alonedynamicallygeneratedGUI

–  UsefulopGonseg-stderr/out

•  EasierinstallaGoncreaGonandupdate–  UsingEclipsemachineryinKNIME_install.py–  eglistofextensionstoinstall,fromseveral(zipped)updatesites

SchrödingerextensionsSeedetailsin:

•  h#p://www.schrodinger.com/upload/KNIME_Overview.pdf

•  Thenewfeaturesslides:–  Parameterflowvariables(2014-1)–  SimplifiedbatchexecuGon(2013,2014-1)–  Chemistryexternaltoolnodeimprovements–  KNIMEmenuinMaestro(2012)–  Start-upscript(2012)

•  Workflowexamples:–  Labs>Parameterflowvariableusage–  General>InstallaGon(KNIME_install.pyscenarios)–  General>Workflowlist–  General>Chemistryexternaltoolnodeusage–  Phase>Shapescreening,docking(batchexecuGon)–  2Drendererinthereportdesigner

WhyuseKNIMEAutomation -  Automate repetitive tasks (especially complex /

error prone tasks) -  e.g. PDB set preparation, Ligand database

preparation

CollaboraDon-  Shareworkflowswithcolleagues(alsoinMaestroand

Seurat)-  Notablackbox

-  e.g. Ensembledocking,HTSanalysis

Prototyping-  Testparameters

-  e.g. Validatedockingparameters

DocumentaDon-  Easydebugging,interrupGons,dataincluded,inspect

eachstep(2D,inMaestro/PyMOL)

CombinevariousTools-  Schrodingerandthirdpartytools(vendoragnosGc),

scripts(Python,Java,shell),-  e.g. QMworkflows

ReporDng-  NodesforreporGngresults

-  e.g. Enrichmentplo#ernode,pdf,tables,etc.-  KNIMEreportdesigner(free),webportal

(KNIME.com)

Inexpensive

Overview•  Organizedbylevel:

– Getstarted–  Intermediate– AdvancedfuncGonaliGes

•  Andbytopics:– KNIMEdesktop:GUI,specificiGes,nodes– Schrödingerextensions:specificiGes,nodes

•  YoucanjumpbetweenthesecGonsusinglinks(markedwith►or◄).Seetheoverviewslides.

•  Therearealsolinkstouse-caseexamples(markedwith♦).

GetstartedKNIMEdesktop

– GUI ► – SpecificiGes ► – Nodes ►

Schrödingerextensions– SpecificiGes ► – Schrödingernodes ►

►Intermediate

KNIMEdesktopGUI ◄ •  Knime.organdKnime.com•  KNIMEdesktop•  StartKnime•  Createanewworkflowandorganizeaworkspace•  Runanode•  Importandexportworkflows•  Tipsandtricks •  DocumentaGon

KonstanzInformaDonMinerandEcosystemKNIME.org -  Leading open-source ‘pipelining/workflow’ tool -  Freely available to academic and industrial researchers -  KNIME Desktop, based on Eclipse h#p://www.knime.org -  Community contributions:

-  Modeling tools -  Marvin sketcher -  RDKit -  Indigo -  CDK -  R Scripting -  Erlwood -  Image Processing -  HCS Tools -  Next Generation Sequencing -  Palladian (mainly GPL3)

KNIME.com Enterprise products and Services h#p://www.knime.com -  Report designer (free) -  KNIME team space (share workflows) and KNIME server (web portal and SOA access) -  Cluster execution (scalability) -  KNIME professional (support, maintenance and training) -  Commercial development

KNIMEExtensions15+ Extension Providers Extensible, cross-platform, vendor neutral:

Schrödinger, CCG, Tripos, ChemAxon/Infocom, BioSolveIT, Cresset, Dotmatics, Molecular Discovery, Molegro…

Schrödinger Extensions -  First released in 2007 -  150+ nodes

-  Molecular mechanics -  Molecular dynamics -  Quantum mechanics -  Cheminformatics -  Pharmacophore modeling -  Combinatorial libraries -  Docking -  Protein structure prediction -  Structure and data manipulation

-  Maestro integration -  Workflow execution -  Structure exchange

KNIMEDesktopGUI•  Fullscreenmode

•  ForgetaboutEclipsespecificmenuitems

Moreabout:

•  Theconsole ►

StartKNIME•  StartupKNIME:

–  OnLinux:run$SCHRODINGER/knime–  OnWindows:clickontheicon–  Use-dataMyWorkspacetoopenaspecificworkspace–  File>Switchworkspace,butKNIMEtakesGmetostartupagain

•  Workspace,workflowsandworkflowgroups:

Createanewworkflowandorganizeaworkspace•  Underthepop-upmenuofWorkflowProjectrepository:

–  NewKNIMEworkflowandNewWorkflowgroup–  Copy,Paste,Delete,Move,Rename

•  DraganddroptheworkflowsintheWorkflowprojectrepository

Runanode

doubleclickorpop-up

•  Connectors•  Nodestatus

•  Inputandoutputdatatables

Importandexportworkflows•  File>ImportKNIMEworkflow/ExportKNIMEworkfloworunderthepop-upmenuofaWorkflowProjectgroup

•  Importfromanotherworkspaceoranarchivefile(zip)•  Select1orseveralworkflows>exportasazipfileExcludeornotthecacheddatafromtheexportedfile

Tipsandtricks•  Saveregularlythechanges.SinceKNIME2.10thereisanautosavefuncGonalitybutitisn’tonbydefault.SavewhilerunningcalculaGons(seePreferences►)

•  MulGpleundoandredoapplyonworkflowediGon(execuGondatalostthough)

•  TheKNIMEdesktopisn’tbasedonaclient-serverarchitecture.IfyouclosetheKNIMEinstancewhileacalculaGonisrunningitwon’tkillitnoryouwillbeabletorecovertheresultswhenopeningtheworkflowagain.

DocumentaDon•  NodedescripGons.AlsoaccessiblefromHelp>Helpcontent>Knime>NodedescripGonsTypeinsearchfieldandinspecttheconfiguraGonpanel

•  Productpage h#p://www.schrodinger.com/KNIME-Extensions NewFeatures,NewFeaturesSlides,KNIMEOverview

•  SchrödingerKNIMEmanual $SCHRODINGER/docs/knime/user_manual/kni13_user_manual.pdf•  SchrödingerFAQs h#p://www.schrodinger.com/kb•  Workflowpage(examples) h#p://www.schrodinger.com/knimeworkflows/•  Schrödinger’sextensionswebex h#p://www.schrodinger.com/seminarprior/19/24/•  KNIME.org

– Workflowexamples (preconfiguredserveraccessinKNIMEexplorer)–  Screencast h#p://www.knime.com/introducGon/screencasts–  Forum h#p://www.knime.org/forum/

KNIMEdesktopGUI ► •  Preferences•  AdvancednodefuncGonaliGes•  Errors,warningsandConsoleinformaGon•  Flowvariablesandworkflowvariables•  Metanodes•  Memorylimit•  Tipsandtricks

KNIMEdesktopspecificiDes ◄ •  StepwiseexecuGon•  Datatablecolumntypesandconversion

StepwiseexecuDon•  OnlystepwiseexecuGon IdealtotakeadvantageofSchrödinger’sjobcontrolinfrastructure

•  NopredefinedexecuGonorderfornonconnectedbranches.Usetheflowvariableports[KNIME2.3]

•  Datacachedateachstep•  Preferences>KNIME>Maximumworkingthreadsfarallnodes•  1:1connecGonbetweennodes(usetheconcatenatenodetocombineinputflows)

Datatablecolumntypesandconversion•  KNIMEreliesonstrictdatatablecolumntyping•  Converternodes:

– DoubletoInt(integer),Stringtonumber,Numbertostring – Moleculetypecast(butnoMaestroconversion)– Openbabel,CDKtomolecule,MoleculetoCDK

•  IntheSchrödingerextensions:– String-to-type– Molecule-to-MAE,MAE-to-Pdb,MAE-to-SD,MAE-to-Smiles,MAE-to-mol2,SD-to-smiles

– Canvasobjectconverters

Schrödingerspecificcelltypes•  Structures:Maestro,Sequence,Alignment•  Severalfiles:Glidegrid,PhaseHypothesis•  Desmondtrajectory•  Binaryformats:CanvasfingerprintandmatrixReadersandwriters,converters

KNIMEworkbenchnodes ◄ •  KNIMEworkbenchnodes•  DatamanipulaGonnodes•  Dataexchange

KNIMEworkbenchnodes•  I/OnodesforreadingandwriGngdatafromfilesanddatabases

•  DatamanipulaGonnodesformanagingtheinternaldatatablesthatareusedtopassinformaGonbetweennodes

•  CharGngandplopngtools•  Loopsupport,GmeSeries,Distancematrix•  StaGsGcsanddataminingnodes(Mining,Weka)suchasclustering,neuralnetworks,decisiontrees,LibSVMRstaGsGcalcomputaGon

•  Basicchemistry-awarenodes(CDK)verylimited,seeSchrödingerextensionnodes►

ThemostoPenusednodesfordatamanipulaDon•  Rowfilter,Rowspli#erandSorter•  Columnfilter,Columnresorter,ColumncombinerandRename•  Joiner(seealsoSchrödingerLookupandaddcolumnnode►)andConcatenate

(only2inputs)

Andalso:•  Javasnippet,RowIDandGroupBynode ►•  SchrödingernodesfordatamanipulaGon ►

Dataexchange•  Astextfiles:Filereaderandcsvwriternodes•  InExcelformat:xlsreaderandxlswriternodes•  Betweenworkflows:tablereaderandtablewriternodes

•  SeealsoamongtheSchrödingernodes:

– Schrödingerreaderandwriternodes– CSVreader(readseveralfiles)– ViewCSV ►

KNIMEworkbenchnodes ► •  KNIME.comLabsnodes•  ScripGngandrunathirdpartytool•  Javasnippet•  RowID•  Groupby•  Miscellaneousnodes:InteracGvetable,Mathformula,CDKSketcher•  PlopngfaciliGes•  LoopingfuncGonaliGes-Basics•  Modelbuildingnodes

SchrödingerextensionsspecificiDes ◄ •  Canvas2Drenderer•  Groupedstructuresinacell•  OutputcolumnstructureopGons•  Jobcontroltab

Canvas2Drenderer•  Preferences>KNIME>Preferredrenderer

Groupedstructuresinacell•  #CTs:numberofstructures•  SetofconformaGons,Glideposes,Ligprepforms…•  Groupandungroupnodes,matchopGon•  AlsogroupedSD,mol2

OutputcolumnstructureopDons•  InputplusOutput,OutputreplacesInput,Outputonly•  ExtractMAEproperGes,SetMAEproperGesanddeleteMAE

properGesnodes.

CTs: Structures + properties

CTs, columns new CTs and/or new columns KNIME

Schrödinger tools New CTs

Extract mae properties

Set mae properties

Reader Writer, Maestro

Delete mae properties

OutputcolumnstructureopDons

Jobcontrol

SchrödingerextensionsspecificiDes ► •  Schrödinger preferences •  Start-up script options •  Access to flow variables

Schrödingernodes ◄ •  Schrödinger node repository

•  Configuration panel visual coherence

•  Nodes of general use: –  Readers and converters –  Run Maestro and Run Maestro command –  Structure manipulation –  Data manipulation and viewers –  Scripting

•  KNIME workflow webpage

AccesstoSchrödingertoolsviaKNIME•  RunonLinux,MacandWindows

32and64bit•  AddourextensionstoanexisGngKNIME

installaGonusingtheupdatesite•  150+nodescoveringthewholeSchrödinger

Suite

CheminformaDcsFingerprintBasedTools

-FingerprintGeneraGon-GeneratePairwiseMatrix-GeneratePairwiseMatrix(2Inputs)-SimilarityMatrix(fromMolecules)-DissimilaritySelecGon(fromMatrix)-BuildReportforClustering(fromMatrix)-HierarchicalClustering(fromMatrix)

FiltersandMiningTools-MaximumCommonSubstructureSearch-SubstructureSearch-REOSFilter-StructureFilter

UDliDesandConverters-PrincipalComponents-MulG-dimensionalScaling-CombineFingerprints-ConcatenateBitvectors-ConvertFingerprinttoBitvector-ConvertFingerprinttoTable-ConvertMatrixtoTable-ConvertTabletoFingerPrint-ConvertTabletoMatrix-ConvertBitvectortoFingerPrint

Modeling-BayesClassificaGonModelBuilding

MolecularMechanics-MacroModelSinglePointEnergy-MacroModelMinimizaGon-MacroModelCoordinateScan-ConfGenStandard-ConfGen-ConformaGonalSearch-ConformaGonalSearchandCluster-Premin-Impref-UffminQuantumMechanics-JaguarSinglePointEnergy-JaguarMinimizaGon-NMRShieldingConstants-JaguarCharges

PharmacophoreModeling-PhaseShape-PhaseDBQuery-PhaseFileQuery-PhaseDBCreaGon-PhaseHypothesisIdenGficaGonDockingandScoring-GlideGridGeneraGon-GlideLigandDocking-GlideMulGpleLigandDocking-XPVisualizer

Post-processing-PrimeMM-GBSA-EmbraceMinimizaGon-StrainRescore-PoseEntropy-PoseFilter-GlideEnsembleMerge-GlideMerge-GlideSortResults

ProteinStructurePredicDon-BLAST-PrimeBuildHomologyModel-PrimeSideChainSampling-PrimeMinimizaGon

SchrödingernodesWorkflowsProteinPreparaGon-ProteinPreparaGonWizard-ProteinAssignmentInduced-fitdocking-IFDandindividualstepsLigandPreparaDon-LigPrep-Ligprepindividualtools(Ionizer,

Desalter,Neutralizer…)-EpikPropertyGeneraDon-QikProp-MolecularDescriptors-CalculateproperGesFiltering-Ligfilter-Ligparse-PropertyFilter(Propfilter)

Readers/Writers-CSVReader-MoleculeReader-SD,PDB,Mol2Readernodes-SequenceReader-AlignmentReader-FingerprintReader-HypothesisReader-GlideGridReader-GlideMulGpleGridReader-VariableBasedGlideGridReader-MoleculeWriter-SequenceWriter-AlignmentWriter-HypothesisWriter-FingerprintWriterConverters-Molecule-to-MAE-MAE-to-Pdb,to-SD,to-Smilesandto-Mol2-SD-to-Smiles-PoseViewer-to-Complexes-Complexes-to-PoseViewers-String-to-Type-Hartree-to-kcal/molConverter-kJ-to-kcalConverter

Desmond-Systembuilder-MolecularDynamics-TrajectoryextractframesandmanipulaGon-Trajectoryreader,CMSreaderReporDng-RunMaestro-RunCanvas-ViewCSV(openxls/ooffice)-TextViewerToolsCombinatorialLibraries-CombiGlideLibraryEnumeraGon-CombiGlideReagentPreparaGonFragments-FragmentJoiner-FragmentsfromMoleculesDataManipulaDon-CompareLigands-LookupandAddColumns-GroupMAE-UngroupMAE

StructureManipulaDon-AddHydrogens-DeleteAtoms-SplitbyStructure-MAEParser-ExtractMAEProperGes-DeleteMAEProperGes-SetMAEProperGes-SetMoleculeTitle-SetMAEIndexUDliDes-GetPDB-AlignBindingSites-ProteinStructureAlignment-PrimeFix-RMSD-AssignBondOrders-UniqueTitleCheck-PDBName-SDFormatChecker-GenerateSmarts-UniqueSmiles-EntropyCalculaGon-RRHOEntropy-BoltzmannPopulaGon-VolumeOverlapMatrix

ScripDng-RunMaestroCommand-ChemistryExternalTool0:1,1:0,1:1,

1:2,2:1and2:2nodes-PythonScript0:1,1:0,1:1,1:2,2:1and

2:2nodes

VisualCoherence–Maestrovs.KNIME

Read in Ligands

Ligand Preparation

Filtering

Read in Grid

Docking

View Results

Nodesofgeneraluse-Readersandconverters•  Moleculereader,SDreader...Glidegridreader...•  Converters(Maestro,mae.gz,SD,sd.gz,mol2,PDB,smiles)includingMoleculeto

MAE,stringtotype.Canvasconverters(Matrix,Fingerprint,Bitvectorfromandtotable).SDformatchecker

•  PoseviewertocomplexesandComplexestoPoseViewer

RunmaestrocommandandRunMaestro

Nodesofgeneraluse-StructuremanipulaDon•  SetMAEproperGes

•  ExtractMAEproperGes

Nodesofgeneraluse-StructuremanipulaDon•  ExtractandSetMAEproperGes•  GroupandUngroup,SetMAEindex•  MAEparser•  Splitbystructure,Deleteatoms•  Compareligands•  Uniquesmiles,UniqueGtlecheck,Ligfilter,Alignbindingsites,RMSD,Volumeoverlapmatrix...

Nodesofgeneraluse-DatamanipulaDonandviewers•  Lookupandaddcolumns•  RunSpreadsheetviewer(OpenOffice/Excel)•  Tableviewer

KNIMEWorkflowsAvailableforDownload

http://www.schrodinger.com/knimeworkflows

OtherKNIMEWorkflowsCheminformaDcs•  ClusterbyFingerprint•  DatabaseAnalysis•  MaximumCommonSubstructureSearch(MCS)•  SelectDiverseMolecules•  SimilaritySearch•  SubstructureSearch

DockingandPost-Processing•  DockingandScoring•  EnsembleDocking•  LoopOverDockingParameters•  ProteinPreparaGonandGlideGridGeneraGon•  ValidateDockingParameters•  VirtualScreening•  SiteMap

PharmacophoreModeling•  PhaseHypothesisIdenGficaGon•  PhaseScreening•  ShapeScreening

MolecularDynamics:

•  DesmondSimulaGon

MolecularMechanics

•  CompareConformaGonalSearchMethods

•  ConformaGonalSearchandPost-Processing

Quantummechanics

•  ConformaGonalSearchandQMRefinement

•  ESPCharges

•  JaguarpKa

•  QuantumMechanicalProperGes

•  Semi-empiricalOpGmizaGon

LibraryDesign

•  LibraryEnumeraGon

ProteinModeling

•  InducedFitDockingProtocol

•  ModelBuilding

Workbench

•  GroupByUse-cases

•  GroupLooper

•  Unpivot

RealWorldExamples

•  BindingSiteShapeClustering

•  SitemapandGlideGridGeneraGon

•  VendorDatabasePreparaGon

Labs•  GlideGridWriter•  ParameterFlowVariableUse-cases•  RunMaestro1:1Use-casesGeneraltools•  ChemistryExternalToolUse-cases•  EnsureMoleculeTitleUniqueness•  OutputColumnStructureOpGonPhilosophy•  ProteinStructureAlignment•  PythonScriptNodeUse-cases•  RunMaestroCommandNodeUse-cases•  RunPyMOL•  SplitandAlignMulGmers•  Webservice•  WorkflowsintheCurrentWorkspacehttp://www.schrodinger.com/knimeworkflows/

Schrödingernodes ►

•  Chemistrytoolnodes•  Pythonnodes•  Rowiteratorloopstart•  Lookupandaddvs.Joinernode•  Miscellaneousnodes:Compareligands,SetmoleculeGtle

Intermediate

KNIMEworkbench-GUI ►-Nodes ►

Schrödingerextensions

-SpecificiGes ►-Schrödingernodes ►

◄ Getstarted►AdvancedfuncGonaliGes

KNIMEworkbenchGUI ◄ •  Preferences•  AdvancednodefuncGonaliGes•  Errors,warningsandConsoleinformaGon•  Flowvariablesandworkflowvariables•  Metanodes•  Memorylimit•  Tipsandtricks

Preferences>KNIME•  Directoryfortemporaryfiles(SeealsoSchrödingerpreferences ►)•  KNIMEGUI-disablethenodereset,deleGonandreconnecGonconfirmaGon•  KNIMEGUI-Consoleviewloglevel:recommendedtochangetoINFO.ExampleofinformaGonprovidedbySchrödingernodes►

AdvancednodefuncDonaliDes•  Hoveringoveraninputconnectortellsyouwhatthenodetakesasinput(egMoleculesinMaestro,SMILESorSDformat)

•  Hoveringoveranoutputconnectorreportsthenumberofrowsandcolumnsintheoutputtable

•  Commentaworkflow:Nodepop-upmenu>NodenameanddescripGon•  Datatable>changetherenderer

Errors,warningsandConsoleinformaDon•  Popup-menu>ViewStdoutput/error•  WarningsignabovethenodestatuswhenthenodecompletedwithpotenGalerrors.

•  ConsoleinformaGon:INFO HierarchicalClusteringNodeModel Preparinginputfile'/tmp/HierarchicalClustering_in_423741.mat'

INFO HierarchicalClusteringNodeModel FinishedpreparingfileGme0.35seconds

INFO HierarchicalClusteringNodeModel 10:42:4511.17.2009:

Runningcmdline[0]='=/usr/local/schro-latest/uDliDes/canvasHC-imHierarchicalClustering_in_4116794508031023741.mat-otHierarchicalClustering_in_4116794508031023741.tree-ogHierarchicalClustering_in_4116794508031023741.csv-linkageschrodinger-n123'

INFO HierarchicalClusteringNodeModel CompletedGme1.626seconds

INFO HierarchicalClusteringNodeModel Preparingoutput

INFO HierarchicalClusteringNodeModel Finishedpreparingoutput:Gme0.06seconds

INFO LocalNodeExecuGonJob HierarchicalClustering(fromMatrix)0:2:50Endexecute(2secs)

Flowvariablesandworkflowvariables•  TheFlowvariablesareusedpassdatabetweennodesontopoftheconnecGons.•  IntheflowvariabletabortheconfiguraGonpanelforacoupleofnodes:

•  Globalvariablescanalsobeset:withtheJavasnippetnode► OrintheWorkflowprojectrepositoryselecttheworkflowandWorkflowvariablesinthe

pop-upmenu.SeealsoSchrödingerspecificiGes►andnodestoeditvariables►

Metanodes•  Tohidethecomplexityandorganizeaworkflow•  Chosethenumberandtypeofinput/output•  Themetanodesopenupinnewtabs

Memorylimit•  Checkthememorylimit:Help>AboutKnime>InstallaGondetails>ConfiguraGonand

searchforalinestarGngwith"eclipse.vmargs=-Xmx"(closetothetop).•  IncreasethememoryallocatedtoKNIME:

–  $SCHRODINGER\knime-maxHeap4096m–  knime–Xmx4096m(aslastopGoninthecommandline)–  in $SCHRODINGER\knime-v*\bin\*\knime.ini: change -Xmx1024M into 2048M (orhigheron64bit)

•  Theerrormessageusuallycontain"Javaheapspace“whenthereisaKNIMEisrunningoutofmemory.

•  Preferences>General>Showheapstatusandusethegarbagecollector.•  KnimeandSchrödingertools(egCanvas)don'tcompeteformemory.

Tipsandtricks•  Copyandpastesomenodestoaspecificplace:Select,copythenodes(Ctrl+C),rightclickwhereyouwanttopastethenodesandselectPasteinthepop-upmenu.UsingCtrl+Vinsteadthenodeswillbepastedali#lebelowtheoriginalones.

•  Thekeyboardshortcutsforitemsonthemenusarelistedasusualwiththemenuitem.InFile>Preferences>General>Keysyoucanviewallthekeybindingstocommands,modifythebindings,andcreateyourownshortcuts.

•  AllthebranchescanberunatthesameGmeusingtheGUItoolbarExecuteallexecutablenodesbu#on.SeealsoCancelallrunningnodes.

Knownissues•  Ifyoucan´tsavetheworkflowwithaJavaheapspaceerrortrytodisconnectthelastnodeorrunthegarbagecollector.

KNIMEworkbenchGUI ► •  Reportdesigner•  Globalvariables•  BatchexecuGon•  Tipsandtricks

KNIMEworkbenchnodes ◄ •  KNIME.comLabsnodes•  ScripGngandrunathirdpartytool•  Javasnippetuse-cases•  ManipulatethetablerowIDsusingtheRowIDnode•  AggregaGonusingtheGroupBynode•  Miscellaneousnodes:InteracGvetable,Mathformula,CDKSketcher•  PlopngfaciliGes•  LoopingfuncGonaliGes-Basics•  Modelbuildingnodes

KNIME.comLabsnodes•  PipelinePilotConnector(otherwayaround?)•  WebServiceclient,etcSpecificupdatesite:h#p://labs.knime.org/

ScripDngandrunathirdpartytool•  Javasnippet► •  JythonandSchrödingerPythonnodes► •  PerlscripGng•  ExternaltoolandSchrödingerChemistryexternaltoolnodes► •  RunMaestrocommands►

Javasnippetuse-cases•  Duplicatenumericorstringcolumns•  Createanewcolumnfromscratch(egatag)•  Combinecolumns(andflowvariables)butusetheCombinernodeforsimple

tasks egreturn"prefix-"+$$FlowVar$$+"_ref_"+$Col1$;

•  Addarowindex(seealsoSetMAEindex)Seethecorrespondingworkflowexample.

ManipulatethetablerowIDsusingtheRowIDnode•  UsedatatablecolumnvaluesasrowIDsandstoreRowIDsinacolumn.Use-cases:– beforetransposingadatatable– SetthelabelstobeusedbythePlo#ernode

•  EnsurerowIDuniqueness– egforCanvastoolsbeforecreaGngamatrix)

AggregaDonusingtheGroupBynodeSomeoftheaggregaGonmethods:

-  first,last

-  max,min

-  Mean

-  Sum

-  Concatenate

-  (unique)count

-  List

-  Set

Miscellaneousnodes•  InteracGvetable:Find&FindNextequivalenttotheSchrödingerTextviewernode

thathavemorefuncGonaliGes

•  Mathformula•  CDKStructuresketcherorMarvinsketch

(freeofchargefromInfocom)

PloingfaciliDes

•  DataViews:Plo#er,Histogram…•  Mining>Scoring:Enrichmentplo#er,ROCcurve•  AdvancedcapabiliGesavailableinKNIMEReportdesigner ►

LoopingfaciliDes-Basics•  Loopstart…Loopend•  Injectandextractvariables•  TableRow/Columntoandfromvariables•  Prebuiltprotocols

•  Schrödingernode:Rowiteratorloopstart►

Modelbuildingnodes

+FutureCanvasnodes

(alreadysomeprototypes)

KNIMEworkbenchnodes ►

•  EditvariablesandadvancedloopingfuncGonaliGes•  HilitefuncGonaliGes•  Databasenodes•  Miscellaneoususefulnodes

SchrödingerextensionsspecificiDes ◄ •  Schrödinger preferences •  Start-up script options •  Access to the flow variables

SchrödingerPreferences•  AspecificscratchdirectorycanbespecifiedforSchrödingernodes•  DeletetemporaryfilesaXeranodesuccessfullyexecutesToggledofftorunthecalculaGonthroughthecommandlineagain

Start-upscriptopDonsTopassuser/machine/OS-specificparameters-maxHeap Maximumheapsize eg2048for2G-maxThreads Maximumworkingthreads-tempDir Schrödingerextensionstemporarydirectory-defaultHost Defaulthost-deleteTempFilestrue/false Deletetemporaryfilesonoroff.-ooCmd<value> Excel/OpenOfficeSpreadsheetcommandegoocalcorC:\ProgramFiles(x86)\MicrosoXOffice\Office12\EXCEL.EXE

Andmore(seeknime–hmessage)

Accesstotheflowvariables•  AccesstotheflowvariablesintheFlowvariabletabincludingtheChemistryexternaltoolsnodes(using%flow_n%)

•  VariablebasedGlidegridreader

Schrödingernodes ◄ •  Chemistrytoolnodes•  Pythonnodes•  Rowiteratorloopstart•  Lookupandaddvs.Joinernode•  Miscellaneousnodes:Compareligands,SetmoleculeGtle,GetPDB

Chemistryexternaltoolnodes•  Input/outputtypes:

– Maestro,SD,mol2,Smiles

– Double,Integer– String,Text–  Sequence,alignment– FingerPrint,CanvasMatrix

– PhaseHypothesis,GlideGrid

Pythonnodes

•  Input/outputconnectors:0:1,1:1,1:2,2:2

•  Schrödinger’sAPIs•  PossibilitytoincludethirdpartyAPIs

Rowiteratorloopstart

Lookupandaddvs.Joinernode•  Takeadvantageonly1column,concatenatecolumnsTheJoinernodeistheeasiestwaytoconcatenatecolumnswhenthetablehavethesamenumberofrowsandsamerowIDs.

Miscellaneousnodes•  GetPDB:easywaytogetoneorseveralstructures usethe|symbolasadelimiterforthelistofcodes

•  SetmoleculeGtle•  Compareligands:themodesareFirstonly,both,either

Schrödingernodes ► •  Simpleworkflowexamples•  Workflowdevelopmentsupportforcustomers•  AutomaGcproteinpreparaGon•  ScienGficallyrelevantapplicaGonoftheworkflowexamples•  InteracGveworkwithKnimeusingtheHiLitefuncGonaliGes•  Useaworkflowagain

Advancedfunc+onali+es

KNIMEworkbench-GUI ►-Nodes ►

Schrödingerextensions

-Advancedworkflowexamples ►

◄ Intermediate

KNIMEworkbenchGUI ◄

•  Reportdesigner•  Globalvariables•  BatchexecuGon•  Tipsandtricks

Reportdesigner•  Fromknime.combutfreeofcharge.IncludedinourdistribuGon•  IncludeToreportnode(s)intheworkflow(can’tbeinmetanodes)andswitchtothe

Reportdesignermode

Reportdesigner-templatemode

Reportdesigner-Canvas2DrendererThestructurescanbeshowninareportusingCanvas2Drendererusingthefollowingprocedure:

•  1.Intheworkflow,addaMAE-to-smilesnodeandaToreportnode.

•  2.InReporGngmode,intheLayouttab,addatabletothereport(draganddropfromtheDatasetview).

•  3.Insertinthe"[smiles]"cell(Table-detailrow)anImagewidgetfromtheReportItemslist.

•  4.Configurethewidget(using"Edit"onthewidget),select"Dynamic image",andpress"Select ImageData..."toselectthesourcecolumn(whichshouldbetheSmilescolumn).Delete"[smiles]"ifyouwantjusttheimageandnoSMILES.YoumaywanttoalterthesizeofthecellbydraggingtheborderverGcallyandhorizontallyifnecessary.

•  5.Changethesizeoftheimagetosomethinglike300x300,whichisdonebyediGngtheDatasetview(rightclick->Edit->Parameters),andchanging(orcreaGngnewParameterstypedasintegeriftheydon'texistyet)theknime-image-heightandknime-image-widthparameters.

•  6.ChecktheviewinthePreviewtab

Globalvariables•  IntheWorkflowprojectlist,right-clickontheworkflow,underWorkflowvariables

BatchexecuDon•  $SCHRODINGER/knime-batch–reset–nosplash-nosave

-workflowFile=<path>/<wkf>.zipor-workflowDir=<path>/<workspace>/<wkf>

•  Altersomesepngs-opDon=nodeNumber,valueName,value,type

-opGon=7,filename,"/tmp/new-molprops.csv",String (int,doubleorString)

FindthenodenumberintheconfiguraGonpanelheader(addthemetanodenumbers)

eg123/456/78forthenode78inthemetanode456inthemetanode123

FindtheopGonnameintheworkspacedirectory:<workflow>/node_name(#7)/node.xml eg:

<configkey="DataURL">

<entrykey="array-size"type="xint"value="1"/>

<entrykey="0"type="xstring"value="/C:/serotonin_unique.sdf"/>

-opGon=2,DataURL\0,"file:/tmp/new-input.mae",String

Whentheinputisanarray

•  Passsomevariables:-workflow.variable=name,value,type(int,doubleorString)

•  WorkflowscanberunfromMaestrousingasimplePythonscriptwrapper

Tipsandtricks•  Rearrangethepanels•  WorkflowMeta-Infos•  TrytoopenaworkflowmodifiedwithanewerversionofKNIMEalterthe2

followinglinesofthefile<workspace>/<workflow>/workflow.knime:<entrykey="created_by"type="xstring"value="2.0.3.0021120"/>

<entrykey="version"type="xstring"value="2.0.0"/>

KNIMEworkbenchnodes ◄ •  EditvariablesandadvancedloopingfuncGonaliGes•  HilitefuncGonaliGes•  Databasenodes•  Miscellaneoususefulnodes

EditvariablesandadvancedloopingfuncDonaliDes

•  Extractvariable(data)andInjectvariable(data)•  TableRowtoVariable(usethefirstrow),VariabletoTableRowandVariabletoTableColumn

HilitefuncDonaliDes•  HiLitefilterandHiLitecollectornodes•  Color,SizeandShapeManager/Appendernodes

Databasenodes•  Seesimpleexamples(notontheWorkflowpageyet)

Timeseriessupport•  Seesimpleexamples(notontheWorkflowpageyet)

Miscellaneousnodes:Cellspliker,Numericbinner•  Referencerowfilter,Referencecolumnfilter,Nominalvaluerowfilter•  Missingvalues•  CreatecollecGoncolumnandSplitcollecGon•  TextmanipulaGon:Stringreplacer,Caseconverter,Cellspli#er•  Rowsampling,ParGGoning,Shuffle•  Numericbinner

KNIMEworkflowexamples ◄

•  KNIMEworkflowpage•  Workflowdevelopmentsupportforcustomers•  WorkflowexamplepresentaGon

Homologymodeling•  ModelbuildingandrefinementLibrarydesign•  LibraryenumeraGonincludingaRunMaestro1:1prototype

RealWorldExamples•  VendordatabasepreparaGonGeneraltools•  Pythonscriptnodeuse-casesincludingaRunPyMOLprototype

•  Chemistryexternaltoolnodeuse-cases•  Runmaestrocommandnodeuse-cases•  OutputcolumnstructureopGonphilosophyKNIMEworkbench•  WorkflowsinthecurrentworkspaceKNIMEworkbench-looper•  GroupLooperSimplest,mostexciDng,newandimprovedworkflows

KNIMEworkflowpage-h#p://www.schrodinger.com/knimeworkflows/

CheminformaDcs•  SubstructureSearch•  Clustering,diversityselecGon,similaritysearch•  Databaseanalysis•  MaximumCommonSubstructureDockingandpost-processing•  ProteinpreparaGon andGlidegridgeneraGon•  Dockingandscoring,Virtualscreening,Ensembledocking,Induced

FitDocking•  Loopoverdockingparameters•  ValidatedockingparametersPharmacophoremodeling•  PhaseShapescreening•  PhasehypothesisidenGficaGon•  Phasedatabasescreening

MolecularMechanics•  CompareconformaGonalsearchmethodsQuantummechanics

•  ConformaGonalsearchandQMopGmizaGonUsingtheReportdesigner

WorkflowdevelopmentsupportforcustomersCombineorexpandtheworkflowexamples•  Hierarchicalclusteringanddiversecompoundsfromeachcluster

WaiDngfornewnodestobedeveloped

•  CombiGlidelibraryenumeraGon,MacroModelcoordinatescan(nowavailable)

•  PCAonperresidueinteracGons (Chemistryexternaltoolnode)

•  DistancemeasurementinproteinandrunscriptinMaestro,descriptorcalculaGon,createproteinmutants(Pythonscriptnode)

Specificworkflows•  VariousMacroModelprotocolsusingthePythonnodeforaccessingadvancedfuncGonaliGes(egcontraints)

•  PrimeMM-GB/SAonasetofcomplexes(liganddetecGon,flexibleresidues)•  SimplifyingcompounddockingwithKNIME,Dr.RobertHappel,BoehringerIngelheim,Vienna

h#p://www.schrodinger.com/seminarprior/19/26/

•  CrisGuimaraesMM-GB/SApaperreproducGonandimprovements

h#p://www.schrodinger.com/Download.php?type=seminarentry&type2=slides&ident=105

•  ProteinpreparaGonprotocol

RealWorldCaseStudy:BindingSiteClusteringandEnsembleDocking

ReallifeapplicaDons...

WorkflowexamplepresentaDonFeelfreetorequestthisotherpresentaGonincluding:•  Simpleexamples•  MoreadvancedexamplesfromtheWorkflowpage•  ScienGficallyrelevantapplicaGons

SchrödingerKNIMEExtensions

KNIMEExtensionsProductManager: Jean-ChristopheMozziconacci

(jcmozzic@schrodinger.com)

VicePresidentofTechnology: VolkerEyrich(volker@schrodinger.com)

MainDeveloper: RavikiranKuppuraj

andthePyDevdevelopmentteam

QA: SimonFoucher

TechnicalSupport: KatalinPhimister,PavelGolubkov

MarkeDng: JarredYacob