What’s New in Discovery Studio 2.5

New features and Usability Enhancements• Anewwelcomepageopenswhenyoustart

theapplicationthatprovidesquickaccesstosamplefiles,guideyouthroughbasictasks,newtutorials,andincludelinkstoimportantinformationsources

• NewDiscoveryGuidesallowyoutocombinescientificalgorithmsand/orexistingDiscoveryStudiofunctionalitytocreatepersonalizedtaskflows

• ViewandmanipulateyourdatainthenewMoleculeWindowdesignedforimprovedperformanceandvisualization

• Filter,sort,tagandeditlargedatasetsintheMoleculeWindowwithoutloadingstructuresintomemoryuntilrequested,whichimprovesperformance

• Viewthe2DchemistryofsmallmoleculesinteractivelywiththeMoleculeWindow,allowingyoutomakeselectionsonathree-dimensionalstructurefromatwo-dimensionalrepresentation

• AutomaticallyextractsequencesandsecondarystructurespropertiesfromPDBandMol2files,enablingyoutoalignstructuraldatasetsbysequenceandsecondarystructurewithoutloadingthe3Dstructuresintomemory

• Lockthevisibilityofindividualmolecules

• Undocktabbedwindowsandmanagethemseparatelyoutsideofthemainapplicationwindowframeformultiplemonitoruse

• Convenientlycoloratomswithanewtoolbarcontainingvariousoptions

• Youcannowshowthepi-pi,cation-pi,and

DiscoveryStudio®takesmodelingandsimulationstothenextlevel.Itbringstogetherthepowerofvalidatedscienceonacustomizableplatformfordrugdiscoveryresearch.Fromprojectconceptiontoleadoptimization,DiscoveryStudioincludesadiversecollectionofsophisticatedsoftwareapplicationsallconvenientlypackagedintoasingle,easy-to-useLinux-orWindows-basedenvironment.BecauseDiscoveryStudioisbuiltuponPipelinePilot™,Accelrys’scientificoperatingplatform,anysoftwarethatyouneedcanbeintegratedintotheresearchenvironment,whetherit’ssoftwarefromAccelrys,in-housedevelopers,orothervendors.NotableenhancementsandfeaturessinceDiscoveryStudio2.1arelistedbelow:

sigma-piinteractionswithanewmonitortype,PiInteractions

• AutomaticallyassigncolortodifferentmoleculesusingtheupdatedAtomDisplayStyledialog

• AccessseveralgeneralpurposeprotocolsfromanewfoldertoaddressroutinetasksinDiscoveryStudio.Theseprotocolsincludeligandpreparation,proteinpreparation,filterbySMARTS,ligandefficiencycalculation,molecularpropertycalculation,etc.

• ManyshortrunningprotocolsthatrequireminimalsetupcannowberunasquicklaunchprotocolsfromtheToolsExplorer

New scientific functionality – Fragment Based Design

• Accessanewprotocol,DockFragments(MCSS),toplacefragmentsinareceptoractivesite.ThisprotocolusesthewellvalidatedandpublishedMultipleCopySimultaneousSearch(MCSS)algorithmthatgeneratesacollectionofpositionedandorientedchemicalfunctionalgroupsthatinteractinsomewaywiththebinding-siteregionofamolecule

• Optionallygeneratefragmentconformationspriortodocking

• PerformfragmentminimizationusingCHARMm

• Usepost-processingstepsforclusteringandremovingfragments

• AnalyzeSARdatawithanewprotocol,CalculateLigandEfficiencyprotocol

• CalculateLigandEfficiencywithseveralnormalizationoptions:HeavyAtomCount,AllAtomCount,MolecularWeight,FitQuality,andLigand-LipophilicityEfficiency

New scientific functionality – X-ray

• AccessnewcollectionofprotocolsforbuildingandrefiningmolecularstructuremodelsfromX-raycrystallographicdata

• AccesstheCNX,popularX-rayrefinementprogram,asstandaloneapplicationorascomponentcollection

• GenerateelectrondensitymapsforcrystalstructuresinCNX/CNSformat

• Detectwatermoleculesinanelectrondensitymapofafullyorpartiallyrefinedproteinstructure,andaddthemtotheinitialstructure

• Generateanelectrondensitymapandusethismaptoautomaticallyplaceoneormoreligandsintonon-occupiedX-rayelectrondensitywithreal-spacerefinementoftheligandintoelectrondensity

• Performfullrefinementofacrystalstructurewithasingleworkflow,enablingrigid-bodyminimization,simulatedannealing,coordinateminimization,occupancyminimization,orB-factorminimization

• Validateyourcrystalstructureusingvarioustestcriteria

New scientific functionality – Transmembrane Protein Analysis

• Accessanewtoolpaneltoanalyzeandedittransmembraneproteins.ThepanelincludesasimpletoolforperformingtransmembranehelixidentificationfromproteinsequencesusingaHiddenMarkovModel(HMM)approach

• UsetheTransmembraneProteintoolpaneltoaddimplicitmembranestoaproteinstructurewithcapabilitiestomanuallyedittheorientationandpositionofproteininmembrane

• Automaticallyselectthehelixsegmentsthatareembeddedinsidethemembraneandseparatethemintoindividualchains

• Accesstoseveralenhancementsinprotocolstoworkwithproteininmembraneenvironment.TheAddMembraneandOrientMoleculeprotocolusesCHARMmsolvationmodelstooptimizethelocationofamoleculewithrespecttomembrane

New scientific functionality – ADMET• AccessnewTOPKATmodels,whichprovide

improvementuponpreviousversionsbyusinggreateramountsofdata.Theyarealsobuiltwithmoreadvancedalgorithms,andarealsoextensible

• Addyourowndatatoextendthetoxicitymodelsandimprovetheirapplicabilitytospecificdatasets

New features – Pharmacophore Analysis• RunPharmacophoreDatabaseBuilding

andSearchingprotocolsinparalleltotakeadvantageofmulti-coreandmulti-processorcomputers,resultingingreatlyimprovedperformance

• Viewdetailsofthedatabaseinareportformat,suchasthenumberofmoleculesbuiltandtheaverageconformers

• EasilymapasingleatomtomorethanonepharmacophorefeatureortodesignateafeatureasaNOTfeature

New features – QSAR, Library Design and Small Molecules Analysis• Generateaclassificationdecisiontreewitha

newprotocol,CreateRecursivePartitioning,andviewtheresultsinthenewdendrogramwindow

• AccessenhancedQSARmodelgenerationmethods.Manyofthelearnershaveoptimumpredictionspaceandfeaturetrackingcapabilities

• Accessanewfolder,Conformations,forperformingconformationalsearchingandanalysiswithallmethodsconsolidatedinoneplace

• Useanewprotocol,GenerateConformations,tospecifyasubsetofrotatablebondsfortorsionsearches

• EasilyPerformcalculationstominimizeconformations,eitheringasphaseorinsolutionusingvarioussolvationmodelsandforcefields

• Assessconformationaldiversityandcoverageofsmallmoleculeconformationsusinganewprotocol,AnalyzeConformations.Measurespecificconstraints(suchasdistances,angles,andtorsions)acrossallconformations

• QuicklyexaminetheconformationsofcommoncoresofmoleculesusingthenewAlignbySubstructureprotocol

• DefineasketchedmoleculeasinputfortheEnumerateLibraryprotocol

New features: Receptor-Ligand Interactions and Simulations

• Draw2Dligandinteractiondiagramswithanewtooltocomputearepresentationofathree-dimensionalligand-receptorbindingsite.

• Objectsselectedinthediagramareautomaticallyselectedinotherviews,whichmakesiteasytoselectitemsofinterestinmorecomplexviews.

• ComputetheconformationalentropyoftheligandintheenhancedversionoftheCalculateBindingEnergiesprotocol.Thisaddsatermtoaccountforthelossinconformationalentropyingoingfromthestartingsetofconformationstoasingledockedconformation

• AccessthepopularGOLDdockingprogram,licensedbyCCDC,intheDockLigands(GOLD)protocol

• Accessimprovedperformanceinallofthehigh-throughputdockingprotocolsusingCHARMm

• UsetheupgradedprotocolsintheSimulationfolderforprojectsdealingwithproteinmembranesystemsmoreeffectively.

• Addcustomizedresidues,newatomtypes,andnewparametersdirectlyintotheforcefieldeditor

• Prepareyourliganddatafileswithionizationbasedoncustomizablebusinessrules,tautomerranking,andfiltering.Runthe

0709

PrepareLigandprotocolinparallelforimprovedperformance

New features – Protein Modeling and Analysis• Buildhomologymodelswithupdated

protocols:selectatemplateandfixpartofthemodelstructureaccordingtothattemplate,specifynucleicacidresiduestobecopiedfromtemplatetomodelstructure,etc.

• Modelantibodyloopsbyfixingtheframeworkoftheantibodystructureasitsinputcoordinatesandonlyoptimizetheloopregion.Altertheloopdefinitionandcreategroupsforeachloopontheinputstructureandthenewlycreatedmodels

• Superimposeproteinsstructuresbasedonasetofselectedresidues,e.g.ligandbindingsiteresiduesusingtheenhancedAlignandSuperimposeProteinsprotocol

Documentation Enhancements• Anewcomprehensiveuserguideisavailable

thatprovidesanoverviewoftheproductandhowitcomplimentsotherAccelrysproducts,informationaboutvisualizingandeditingdata,guidelinesforperformingcomputationalanalyses,methodsforextendingtheproductusingscriptingandPipelinePilot,andusefuldeploymentinformation.

• Asetoftutorialsareavailabletowalkyouthroughbasicfeatures,areasoftechnicalexpertise,andadvancedlessonsformodifyingprotocols.

• Thehelpsystemisenhancedtoprovideeasiernavigation,improvedorganization,andbettersearchcapabilities.

Pipeline Pilot Integration Enhancements• CustomizeanyDSprotocolsorcomponents

usingPipelinePilotProfessionalClient,alsoreferredtoastheDSDeveloperClient

• Accessseveralgridenabledprotocolsforhighperformancecomputing.Out-of-theboxsupportforSGE,PBS,LSF

• DScomponentscollectionsarenowinstalledintothefunctionalcategoriesintroducedinPipelinePilot7.5

Product Updates• AccelrysprovidesregularupdatesfortheDS

ComponentCollectionandtheclient.Youcaneasilycheckforupdatesfromtheclientbychoosing“Help|CheckforUpdates”fromthemenubar