Open Access Databases and Datasets
for Drug Discovery Methods Principles in Medicinal Chemistry 1st Edition M. T. Przewosny
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MethodsandPrinciplesinMedicinalChemistry
Editedby R.Mannhold,H.Buschmann,J.Holenz
EditorialBoard
G.Folkers,H.Timmermann,H.vandeWaterbeemd,J.BondoHansen PreviousVolumesoftheSeries
Bachhav,Y.(Ed.)
TargetedDrugDelivery
2022
ISBN:978-3-527-34781-0 Vol.82
Alza,E.(Ed.)
FlowandMicroreactor TechnologyinMedicinal Chemistry
2022
ISBN:978-3-527-34689-9 Vol.81
Rübsamen-Schaeff,H.,andBuschmann,H. (Eds.)
NewDrugDevelopmentfor KnownandEmergingViruses
2022
ISBN:978-3-527-34337-9 Vol.80
Gruss,M.(Ed.) SolidStateDevelopmentand ProcessingofPharmaceutical Molecules
Salts,Cocrystals,andPolymorphism
2021
ISBN:978-3-527-34635-6 Vol.79
Plowright,A.T.(Ed.)
TargetDiscoveryandValidation MethodsandStrategiesfor DrugDiscovery
2020
ISBN:978-3-527-34529-8
Vol.78
Swinney,D.,Pollastri,M.(Eds.) NeglectedTropicalDiseases DrugDiscoveryand Development
2019
ISBN:978-3-527-34304-1 Vol.77
Bachhav,Y.(Ed.) InnovativeDosageForms DesignandDevelopmentat EarlyStage 2019
ISBN:978-3-527-34396-6
Vol.76
Gervasio,F.L.,Spiwok,V.(Eds.) BiomolecularSimulationsin Structure-basedDrugDiscovery
2018
ISBN:978-3-527-34265-5
Vol.75
Sippl,W.,Jung,M.(Eds.) EpigeneticDrugDiscovery
2018
ISBN:978-3-527-34314-0 Vol.74
Giordanetto,F.(Ed.) EarlyDrugDevelopment
2018
ISBN:978-3-527-34149-8 Vol.73
EditedbyAntoineDaina,MichaelPrzewosny, andVincentZoete
VolumeEditors
AntoineDaina
SIBSwissInstituteofBioinformatics 1015Lausanne Switzerland
MichaelPrzewosny Borngasse43 52064Aachen Germany
VincentZoete
SIBSwissInstituteofBioinformatics UNILUniversityofLausanneand LudwigInstituteforCancerResearch 1015Lausanne Switzerland
SeriesEditors
Prof.Dr.RaimundMannhold † Rosenweg7 40489Düsseldorf Germany
Dr.HelmutBuschmann Sperberweg15 52076Aachen Germany
Dr.JörgHolenz BIAL-Portela&Ca .,S.A. Av.SiderurgiaNacional 4745–457Coronado Portugal
CoverDesignandImages: SCHULZ Grafik-Design
Allbookspublishedby WILEY-VCH arecarefully produced.Nevertheless,authors,editors,and publisherdonotwarranttheinformation containedinthesebooks,includingthisbook, tobefreeoferrors.Readersareadvisedtokeep inmindthatstatements,data,illustrations, proceduraldetailsorotheritemsmay inadvertentlybeinaccurate.
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©2024WILEY-VCHGmbH,Boschstraße12, 69469Weinheim,Germany
Allrightsreserved(includingthoseof translationintootherlanguages).Nopartof thisbookmaybereproducedinanyform–by photoprinting,microfilm,oranyother means–nortransmittedortranslatedintoa machinelanguagewithoutwrittenpermission fromthepublishers.Registerednames, trademarks,etc.usedinthisbook,evenwhen notspecificallymarkedassuch,arenottobe consideredunprotectedbylaw.
PrintISBN: 978-3-527-34839-8
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Contents
SeriesEditorsPreface xiii
RaimundMannhold–APersonalObituaryfromtheSeriesEditors xvii APersonalForeword xxi
1OpenAccessDatabasesandDatasetsforComputer-Aided DrugDesign.AShortListUsedintheMolecularModelling GroupoftheSIB 1
AntoineDaina,MaríaJoséOjeda-Montes,MaiiaE.Bragina,Alessandro Cuozzo,UteF.Röhrig,MartaA.S.Perez,andVincentZoete
References 30
PartISmallMolecules 39
2PubChem:ALarge-ScalePublicChemicalDatabaseforDrug Discovery 41 SunghwanKimandEvanE.Bolton
2.1Introduction 41
2.2DataContentandOrganization 42
2.3ToolsandServices 45
2.3.1PubChemSearch 45
2.3.2SummaryPages 48
2.3.3LiteratureKnowledgePanel 49
2.3.42Dand3DNeighbors 50
2.3.5ClassificationBrowser 51
2.3.6IdentifierExchangeService 52
2.3.7ProgrammaticAccess 52
2.3.8PubChemFTPSiteandPubChemRDF 53
2.4Drug-andLead-LikenessofPubChemCompounds 54
2.5BioactivityDatainPubChem 56
2.6ComparisonwithOtherDatabases 57
2.7UseofPubChemDataforDrugDiscovery 58
2.8Summary 59 Acknowledgments 60 References 60
3DrugBankOnline:AHow-toGuide 67 ChristenM.Klinger,JordanCox,DeniseSo,TeiraStauth,MichaelWilson, AlexWilson,andCraigKnox
3.1Introduction 67
3.2DrugBank 68
3.2.1OverviewofDrugBank 68
3.2.2DrugBankDatasets 69
3.2.2.1DrugCards:AnOverviewandNavigationGuide 70
3.2.2.2Identification 70
3.2.2.3Pharmacology 71
3.2.2.4Categories 73
3.2.2.5Properties 73
3.2.2.6Targets,Enzymes,Carriers,andTransporters 73
3.2.2.7References 77
3.3Protocols 77
3.3.1GeneralWorkflows 77
3.3.1.1UsingDrugBankOnline’sSearchFunctionality 77
3.3.1.2UsingDrugBankOnline’sAdvancedSearchFunctionality 80
3.3.1.3BrowsingDrugsUsingDrugBankOnline’sDrugCategories 83
3.3.2IdentifyingChemicalsandRelevantSequences 86
3.3.2.1SearchingUsingChemicalStructureSearch 86
3.3.2.2UsingSequenceSearchtoFindSimilarTargets 89
3.3.3ExtractingDrugBankDatasetsforML 93
3.4ResearchUsingDrugBank 94
3.5DiscussionandConclusions 95 References 96
4BioisostericReplacementforDrugDiscoverySupportedbythe SwissBioisostereDatabase 101 AntoineDaina,AlessandroCuozzo,MartaA.S.Perez,andVincentZoete
4.1Introduction 101
4.1.1ConceptofIsosterismandBioisosterism 101
4.1.2Classicalvs.Non-classicalBioisostereandFurtherMolecular Replacements 102
4.1.3BioisostericReplacementinDrugDiscovery 105
4.2ConstructionandDisseminationofSwissBioisostere 106
4.2.1IntentionandRequirements 106
4.2.2BioactivityData 107
4.2.3NonsupervisedMatchedMolecularPairAnalysis 108
4.2.4Database 108
4.2.5WebInterface 109
4.3ContentofSwissBioisostere 111
4.3.1GlobalContent 111
4.3.2BiologicalandChemicalContexts 112
4.3.3FragmentShapeDiversity 113
4.4UsageofSwissBioisostere 115
4.4.1WebsiteUsage 115
4.4.2MostFrequentRequests 117
4.4.3ExamplesRelatedtoDrugDiscovery 117
4.4.3.1UseCases 117
4.4.3.2ReplacingUnwantedChemicalGroups 118
4.4.3.3OptimizationofPassiveAbsorptionandBlood–BrainBarrier Diffusion 122
4.4.3.4ReductionofFlexibility 124
4.4.3.5ReductionofAromaticity/EscapefromFlatland 128
4.5ConclusiveRemarks 133 Acknowledgment 133 References 133
PartIIMacromolecularTargetsandDiseases 139
5TheProteinDataBank(PDB)andMacromolecularStructure DataSupportingComputer-AidedDrugDesign 141 DavidArmstrong,JohnBerrisford,PreetiChoudhary,LukasPravda, JamesTolchard,MihalyVaradi,andSameerVelankar
5.1Introduction 141
5.2SmallMoleculeDatainProteinDataBank(PDB)Entries 142
5.2.1WhatDataareinthePDBArchive? 142
5.2.2DefinitionofSmallMoleculesinOneDep 145
5.3SmallMoleculeDictionaries 146
5.3.1wwPDBChemicalComponentDictionary(CCD) 146
5.3.2ThePeptideReferenceDictionary 147
5.4AdditionalLigandAnnotationsinthePDBArchive 148
5.4.1LinkageInformation 148
5.4.2Carbohydrates 149
5.5ValidationofLigandsintheWorldwideProteinDataBank (wwPDB) 150
5.5.1VariousCriteriaandSoftwareUsedforValidatingLigandinValidation Reports 150
5.5.2IdentificationofLigandofInterest(LOI) 151
5.5.3GeometricandConformationalValidation 152
5.5.4LigandFittoExperimentalElectronDensityValidation 152
5.5.5AccessingwwPDBValidationReportsfromPDBeEntryPages 154
5.5.6OtherPlannedImprovementstoEnhanceLigandValidation 154
5.6PDBeToolsforLigandAnalysis 155
5.6.1LigandInteractions 155
5.6.1.1ClassifyingLigandInteractions 155
5.6.1.2DataAvailability 156
5.6.2LigandEnvironmentComponent 156
5.6.3ChemistryProcessandFTP 158
5.6.4PDBeChemPages 158
5.7Ligand-RelatedAnnotationsinthePDBe-KB 158
5.7.1IntroductiontoPDBe-KB 158
5.7.2DataAccessMechanismsforLigand-RelatedAnnotations 160
5.7.3Ligand-RelatedAnnotationsontheAggregatedViewsofProteins 162
5.8CaseStudy:UsingPDBDatatoSupportDrugDiscovery 164
5.9ConclusionsandOutlook 165
5.9.1UpcomingFeaturesandImprovements 166 References 167
6TheSWISS-MODELRepositoryof3DProteinStructuresand Models 175 XavierRobin,AndrewMarkWaterhouse,StefanBienert,GabrielStuder, LeilaT.Alexander,GerardoTauriello,TorstenSchwede,andJoanaPereira
6.1Introduction 175
6.2SMRDatabaseContentandModelProviders 176
6.2.1PDB 177
6.2.2SWISS-MODEL 177
6.2.3AlphaFoldDatabase 179
6.2.4ModelArchive 180
6.3ProteinFeatureAnnotationandCross-ReferencestoComputational Resources 181
6.3.1StructuralFeatures,Ligands,andOligomers 181
6.3.2SWISS-MODELassociatedtools 182
6.3.3WebandAPIAccess 183
6.4QualityEstimatesandBenchmarking 188
6.5BindingSiteConformationalStates 189
6.6SMRandComputer-AidedStructure-basedDrugDesign 190
6.7ConclusionandOutlook 191 References 193
7PDB-REDOinComputational-AidedDrugDesign(CADD) 201 IdadeVries,AnastassisPerrakis,andRobbieP.Joosten
7.1HistoryandConcepts 201
7.1.1X-rayStructureModels 201
7.1.2PDB-REDODevelopment 202
7.1.2.1FirstUniformity 203
7.1.2.2AutomaticRebuildingofProteinBackboneandSideChains 203
7.1.2.3AutomatedModelCompletionApproaches 204
7.1.2.4SystematicIntegrationofStructuralKnowledge 205
7.1.2.5OverviewofPDB-REDOPipeline 205
7.2StructureImprovementsbyPDB-REDO 206
7.2.1ParametrizationandRebuildingEffectsonSmallMoleculeLigands 206
7.2.1.1Re-refinementImprovesLigandConformation 206
7.2.1.2SideChainRebuildingImprovesLigandBindingSites 207
7.2.1.3HistidineFlipandImprovedLigandParameterization 208
7.2.2BuildingofProteinLoopsandLigandsintoProteinStructure Models 210
7.2.2.1LoopBuildingCompletesaBindingSiteRegion 210
7.2.2.2LoopBuildingResultsinImprovedBindingSites 211
7.2.2.3BuildingnewCompoundsintoDensity 212
7.2.3NucleicAcidImprovementsbyPDB-REDO 213
7.2.4GlycoproteinStructureModelRebuilding 214
7.2.5MetalBindingSites 214
7.2.6LimitationsofthePDB-REDODatabank 216
7.3AccessthePDB-REDODatabankandMetadata 218
7.3.1DownloadingandInspectingIndividualPDB-REDOEntries 218
7.3.2DataAvailableinPDB-REDOEntries 220
7.3.3UsageoftheUniformandFAIRValidationData 220
7.3.4CreatingDatasetsfromthePDB-REDODatabank 222
7.3.5SubmittingStructureModelstothePDB-REDOPipeline 223
7.4Conclusions 223
AcknowledgmentsandFunding 224 ListofAbbreviationsandSymbols 224 References 225
8PharosandTCRD:InformaticsToolsforIlluminatingDark Targets 231
KeithJ.Kelleher,TimothyK.Sheils,StephenL.Mathias,Dac-TrungNguyen, VishalSiramshetty,AjayPillai,JeremyJ.Yang,CristianG.Bologa, JeremyS.Edwards,TudorI.Oprea,andEwyMathé
8.1Introduction 231
8.2Methods 233
8.2.1DataOrganization 233
8.2.1.1TargetAlignment 234
8.2.1.2DiseaseAlignment 234
8.2.1.3LigandAlignment 234
8.2.1.4DataandUIUpdates 235
8.2.2ProgrammaticAccessandDataDownload 235
8.2.3UIOrganization 235
8.2.3.1ListPages 236
8.2.3.2DetailsPages 236
8.2.3.3Search 238
8.2.3.4Tutorials 240
8.2.4AnalysisMethodsWithinPharos 240
8.2.4.1SearchingforLigands 240
8.2.4.2FindingTargetsbyAminoAcidSequence 241
8.2.4.3FindingTargetswithSimilarAnnotations 241
8.2.4.4FindingTargetswithPredictedActivity 241
8.2.4.5EnrichmentScoresforFilterValues 241
x Contents
8.3UseCases 242
8.3.1HypothesizingtheRoleofaDarkTarget 242
8.3.1.1PrimaryDocumentation 242
8.3.1.2ListAnalysis 247
8.3.1.3DownloadingData 251
8.3.1.4VariationsonthisUseCase 251
8.3.2CharacterizingaNovelChemicalCompound 251
8.3.2.1FindingPredictedTargets 252
8.3.2.2AnalyzingSimilarLigands 254
8.3.2.3LigandDetailsPages 256
8.3.2.4VariationsonthisUseCase 257
8.3.3InvestigatingDiseases 260
8.4Discussion 262 Funding 264 References 264
PartIIIUsers’PointsofView 269
9MiningforBioactiveMoleculesinOpenDatabases 271 GuillemMacip,JúliaMestres-Truyol,PolGarcia-Segura, BryanSaldivar-Espinoza,SantiagoGarcia-Vallvé,and GerardPujadas
9.1Introduction 271
9.2MainToolsforVirtualScreening 272
9.2.1ADMETandPAINSFiltering 272
9.2.2Protein–LigandDocking 274
9.2.3PharmacophoreSearch 275
9.2.4Shape/ElectrostaticSimilarity 276
9.2.5Protein-StructureDatabases 277
9.2.6TheProteinDataBank 278
9.2.7ThePDB-REDODatabank 278
9.2.8TheSWISS-MODELRepository 279
9.2.9TheAlphaFoldProteinStructureDatabase 279
9.3ValidatingBindingSiteandLigandCoordinatesinThree-Dimensional ProteinComplexes 280
9.4DatabasesforSearchingNewDrugs 281
9.4.1COCONUT 281
9.4.2GDBs 282
9.4.3ZINC20 282
9.5DatabasesofBioactiveMolecules 282
9.5.1TheBindingDBDatabase 283
9.5.2PubChem 283
9.5.3ChEMBL 284
9.6DatabasesofInactive/DecoyMolecules 285
9.6.1CollectingExperimentallyInactiveCompoundsfromPubChem 285
9.6.2CollectingPresumedInactiveCompoundsfromDecoyDatabases 285
9.6.3BuildingCustom-BasedDecoySets 286
9.7MainMetricsforEvaluatingtheSuccessofaVirtualScreening 286
9.8ConcludingRemarks 288
References 289
10OpenAccessDatabases–AnIndustrialView 299 MichaelPrzewosny
10.1Academicvs.IndustrialResearch 299
10.2Scaffold-Hopping 310
10.3Virtual-Screening 311
Abbreviations 312
References 313
Index 317
SeriesEditorsPreface
Theworkofnaturalscientistsinallscientificdisciplineshaschangedalotinthe recentdecade.Accesstoinformationanddatainscientificdatabaseshasbecome essentialforeffectiveandefficientwork.Inadditiontothecommercialdatabases fromprofessionalproviders,openaccessdatabasesfromassociationsandinstitutes havealsobecomeincreasinglypopularformedicinalchemistsinacademiaandpharmaceuticalindustry.
Thelatestvolumeofourbookseriesentitled“OpenAccessDatabasesandDatasets forDrugDiscovery”providesanexemplaryoverviewofsomeofthemostimportant databasesandapplicationsthatshouldbeofgreathelptothemedicinalchemistry communityasinformationsourceandmotivationtoexplorethegrowingandexistingfieldofopenaccessdatabasesandusefuldatasets.Thebooksurelywillsupport alltypeofscientistsworkinginthefieldofdrugdiscoveryandmedicinalchemistry whoneedinformationfromdatabasestosupporttheirwork.
Itallstartedinthelate2010swhenRaimundMannholdsuggestedthistopicinour annualeditormeetingsasalong-cherishedheart’sdesire.Andin2019hewassuccessfultoconvinceAntoineDainaandVincentZoete,whoarewell-knownscientists inthisfield,toeditsuchabook.
Afterindustrialpracticeascomputationalchemistforagrochemicalresearchand academicexperienceaslecturerandresearcherindrugdiscovery,Antoinejoined theSIBSwissInstituteofBioinformaticsin2012.Heisnowseniorscientistin theMolecularModelingGroupinchargeofmethodologicaldevelopmentsinthe SwissDrugDesignprogram,ofsupportingdrugdiscoveryprojectsandofteaching computer-aideddrugdesign.
VincentjoinedtheSIBSwissInstituteofBioinformaticsin2004.HewastheassociategroupleaderoftheSIBMolecularModelingGroupuntil2017andthengroup leaderfrom2017untilnow.Besidesthis,VincentisAssociateProfessorinmolecularmodelingattheUniversityofLausannesince2022andcoordinator/developer ofSwissDock.ch,SwissParam.ch,SwissBioisostere.ch,SwissTargetPrediction.ch, SwissSimilarity.ch,andSwissADME.ch.
TheSwissInstituteofBioinformaticshostingtheClick2DrugWebpageprovides themostcomprehensivecollectionofworldwideavailabledatabasesandapplication toolsinthefieldofdrugdiscovery.
AtthesametimeHelmutBuschmannrememberedhisoldcolleagueMichael PrzewosnyfromourtimetogetheratGrünenthalGmbHlocatedinAachen.Michael hasover20yearsofexperienceinpharmaceuticalresearchanddrugdiscovery. Heheldseveralpositionsaslaboratorymanagerinmedicinalchemistryand processdevelopment.Michaelhascreatedacompetitiveintelligencedepartmentat GrünenthalinAachen,wherehewasresponsibleforsuchdatabaseandapplication toolsasservicefortheentireresearchorganization.Ittooksometimetoconvince Michaelforsuchabookassignment,butfinallyhewasmotivatedtojointhegroup ofAntoineandVincent.
Togethertheybroughtmanyyearsofexperienceinthedevelopmentofsuch databases,reinforcedbymanyyearsofexperienceinusingsuchdatabasesinthe fieldofdrugdiscovery.
JointlyAntoine,Vincent,andMichaelstartedinlate2019withacollectionofideas andagreedafterlongdiscussionsonausefulstructureofsuchabroadresearcharea withanenormousrapiddevelopment.
Afterasuccessfulstart,therewasnowalong,rocky,andchaoticroadaheadof themaccompaniedbytheCovidpandemic.Thereweremanydisappointments,but theynevergaveup.Theyworkedveryhardandwerealwayssuccessfultofindaway forward.Thenanothermajorsetbackfollowed.Raimunddiedunexpectedlyaftera shortillnessonOctober14,2022,andwasnotabletoseethesuccessfulcompletion. We,theserieseditorsandthepublisher,areallthemorepleasedthattheeditors havededicatedthisvolumetohismemory.Raimundaccompaniedthebookseries fromthefirstvolumepublishedearlyas1993untilhisdeathandwasabletoenjoy thepublishingofvolume81inJune2022“FlowandMicroreactorTechnologyin MedicinalChemistry”editedbyEstherAlza,shortlybeforehepassedaway.
Theeditorsmanagedtoeditabookwiththesupportofthebestauthorsinthefield toprovidetheinterestedreaderwithadetailedoverviewofopen-accessdatabases anddatasetsfordrugsfromearlytolatephasesofthelengthydrugdiscoveryprocess. Insuchrapidlygrowingresearchfield,thepictureofopendatabasesanddatasets remainsalwaysincomplete.
Itisallthemoreimportantthattheauthorsmanagedtoeditavolumethatdepicts awidevarietyofresourcesfromthemostgeneralisttomostspecializedones.Sucha volumecanneverbeacompleteandencyclopediccollectionofallexistingdatabases, butitactsmuchmorelikeguidanceandmotivationtodealwithsuchdatabasesand theresultingpossibilities.Indifferentchaptersthemostrelevanttoolsanddatabases andappsaredescribedbyexplainingcasestudiesandexamplestogetaneasyand directintroductiontousethesetools.
Antoine,Vincent,andMichaelhavemanagedwithgreatpassiontopersuade andencouragetheauthorstoprovideasmuchpracticaladviceaspossiblewith step-by-stepguidesandhelpfulusecasesfortheinterestedreaderofalldisciplines involvedindrughunting,bringingnew,powerful,andsafemedicinestothe patients.Theselectedandcompileddatacollectionofdatabasesandappsprovides astrongcomprehensivebasisasakindofguidedtourthroughtheverydensejungle ofpublicavailablescientificinformation.
Theeditorshavestructuredtheguidancebookin3thematicsectionsand 10chapters.Antoine,Vincent,andMichaelhavenotonlyeditedthebookbut alsocontributedwiththeirlongexperienceandgreatknowledgeasauthorsand co-authorsofsomeofthechapters.
AsageneralintroductiontothevolumeeditedbyAntoineandVincentthemselves withthesupportoftheircoworkers,acomprehensiveoverviewtothetopicanda richannotatedlistofdatasourcesentitled“OpenAccessDatabasesandDatasetsfor Computer-AidedDrugDesign.AShortListUsedintheMolecularModellingGroup oftheSIB”isprovided.ThecoreofthebookpresentedinpartIandIIconsistsof sevendiverseandhigh-qualityresourcespresentedbytheirdevelopers,categorized insmallmoleculesormacromoleculartargetsanddiseases.
PartIisdedicatedtosmallmoleculesandcontainsthreechaptersdescribingthe mostpopulardatabasesinthisfield:
● PubChem:ALarge-ScalePublicChemicalDatabaseforDrugDiscovery,editedby SunghwanKimandEvanE.Bolton.
● DrugBankOnline:AHow-toGuide,editedbyChristenM.Klinger,JordanCox, DeniseSo,TeiraStauth,MichaelWilson,AlexWilson,andCraigKnox
● BioisostericReplacementforDrugDiscoverySupportedbytheSwissBioisostere Database,editedbyAntoineDaina,AlessandroCuozzo,MartaA.S.Perez,and VincentZoete
PartIIfocusesonmacromoleculartargetsanddiseasescomprisingthefollowing chapters:
● TheProteinDataBank(PDB)andMacromolecularStructureDataSupporting Computer-AidedDrugDesign,editedbyDavidArmstrong,JohnBerrisford,Preeti Choudhary,LukasPravda,JamesTolchard,MihalyVaradi,andSameerVelankar
● TheSWISS-MODELRepositoryof3DProteinStructuresandModels,edited byXavierRobin,AndrewWaterhouse,StefanBienert,GabrielStuder,LeilaT. Alexander,GerardoTauriello,TorstenSchwede,andJoanaPereira
● PDB-REDOinComputational-AidedDrugDesign(CADD),editedbyIdadeVries, AnastassisPerrakis,andRobbieP.Joosten
● PharosandTCRD:InformaticsToolsforIlluminatingDarkTargets,editedby KeithJ.Kelleher,TimothyK.Sheils,StephenL.Mathias,Dac-TrungNguyen, VishalSiramshetty,AjayPillai,JeremyJ.Yang,CristianG.Bologa,JeremyS. Edwards,TudorI.Oprea,andEwyMathé
PartIIIofthebookisdedicatedtouser’spointofviewworkinginacademiaand pharmaceuticalindustrywithtwochapters:
● MiningforBioactiveMoleculesinOpenDatabases,editedbyGuillemMacip, JúliaMestres-Truyol,PolGarcia-Segura,BryanSaldivar-Espinoza,Santiago Garcia-Vallvé,andGerardPujadas
● OpenAccessDatabases–AnIndustrialView,editedbyMichaelPrzewosny Overall,afteralonganddifficultjourneyanoutstandingcollectionofdatabaseand datasetinformationisprovidedthatwillenabletheinterestedreaderaneasystartto usesuchtoolsortoexpandtheirscopebyanextensionofthepreviousapplication.
Withthis,we–theserieseditors–sincerelybelievethatreaderswouldbehighly benefitedfromthecontentsofthisbook.
WewouldliketothankAntoine,Vincent,andMichaeltoputthebrilliantcontributionsoftheauthorstogetherandtoguidethemthroughanadventurousjourney; allauthorsfortheirbrilliantcontributionsandtheirpatience;andFrankWeinreich, StefanieVolk,andtheircoworkers,especiallyAswiniM.fromthecontentanalysis andrefinementteam,fortheirgreatsupporttomakethisbookfinallypossible.
Aachen,Porto,andBonn,July2023
HelmutBuschmann
JörgHolenz
ChristaMüller
RaimundMannhold–APersonalObituaryfromtheSeries Editors
Source:http://www.raimund-mannhold.de/curriculum-vitae/
RaimundMannholddiedonOctober14,2022,afterashortandseriousillnessat theageof74.Nevertheless,thenewsofhisdeathcameasagreatsurprisetohis immediatefamilyandtous.Raimundaccompaniedthebookseries“Methodsand PrinciplesinMedicinalChemistry”fromthefirstvolumepublishedasearlyas1993 untilhisdeathandwasabletoenjoythepublishingofvolume81inJune2022entitled“FlowandMicroreactorTechnologyinMedicinalChemistry”editedbyEsther Alza,shortlybeforehepassedaway.
Establishedin1993,theseries“MethodsandPrinciplesinMedicinalChemistry” hasbecomeacrucialsourceofinformationwithinthemedicinalchemistrycommunityandbeyond.Authorsandeditorsoftheseriescomefrompharmaceutical industryaswellasfromacademicinstitutions,fosteringamoreactiveexchange betweenthesedomains.
Overtime,Raimundfoundsupportfromanumberofinternationallyrenowned expertsandentrepreneursinmedicinalchemistry.PovlKrogsgaard-Larsen,Hendrik Timmerman,HugoKubinyi,andGerdFolkersasretiredserieseditorshadadecisive influenceonthebookseriesand,likeRaimund,havecontributedtoitbecominga figureheadformedicinalchemistryworldwide.
ThefollowingpictureshowsRaimund(middle)withGerdFolkers(left)andHugo Kubinyiduringthecelebrationofthe25thvolumeofthebookseriesin2005.
xviii RaimundMannhold–APersonalObituaryfromtheSeriesEditors
Source:Wiley-VCH
Fromtheverybeginning,theseriesfocusedontopicalvolumescoveringhotconceptsandtechnologies,andthereaderwillnotmissanyimportanttopicinthe field.Therangeoftopicsisasdiverseasarethechallengesfacingmoderndrug developers,spanningthefieldsoforganicchemistry,pharmacology,toxicology,life science,andanalytics,thelatteralsoincludingbioinformatics,chemoinformatics, andproteomics.
Raimund’sheartbeatforhisbookseries,andhewasnowtheonlyfoundingeditor sincethepublicationofthefirstvolume30yearsago(1993);nowitmustliveon withoutRaimund,notasbefore,butitwillcontinuetoliveoninordertopreserve hislegacy.ThatistheobligationofthecurrentserieseditorsChristaMüller,Jörg Holenz,andHelmutBuschmann.
Ourcommongoalwastobeabletocelebratevolume100together;wewerejust abletopublishvolume81together,butwithoutRaimund,withouthiscommitment, andwithouthisstrongwilltodocumenttheknowledgeofmedicinalchemistryof ourtime,itwillbenotaneasytasktocontinueasusual.Withouthimthereisahard roadaheadofustofulfillhislegacyandwithgreatsadnesstocontinuewithouthim. Butweseeatthesametimeitasagreatobligationtocontinuethebookseriesinhis spirit.
Raimund’slifewasshapedbypharmaceuticalscience.Hewasbornin1948in Haltern(NorthRhineWestphalia,Germany).From1970to1973hestudiedpharmacyattheFrankfurtUniversity,receivedhisdoctoratein1977fromtheUniversityofDüsseldorf,andin1982RaimundreceivedtheVeniaLegendiforthesubject
RaimundMannhold–APersonalObituaryfromtheSeriesEditors xix
Physiology.In1990hewaspromotedtotheprofessorofMolecularDrugResearch atHeinrich-HeineUniversityinDüsseldorfuntilhisretirementonJuly9,2012. Themostimportantstagesofhisscientificcareercanbesummarizedasfollows1 :
1970–1973
October1973–September1987
July1977
December1982
StudyofPharmaceuticalSciencesattheJohann-Wolfgang vonGoetheUniversitätFrankfurt/Main
ScientificassistantattheDepartmentofClinicalPhysiology, Heinrich-Heine-UniversitätDüsseldorf
PhDattheDepartmentofClinicalPhysiology (Heinrich-Heine-UniversitätDüsseldorf,Prof.Dr.R. Kaufmann).Thesis:InvestigationsontheCa-antagonistic modeofactionandthestructure-activityrelationshipsof verapamil
Habilitation,conferredbytheMedicalFacultyofthe Heinrich-Heine-UniversitätDüsseldorf.Titleofmonograph: Ca-antagonistsofthealiphaticaminetypeandstructurally relatedheart-activedrugs–investigationson pharmacologicalandphysicochemicalproperties
Since1984 ContributingEditorof“DrugsofToday”and“Drugsofthe Future”
January1989–October1990
November1990–July2012
Since1993
GuestscientistattheDepartmentforPharmacochemistry, VrijeUniversiteit,Amsterdam,NL(Prof.Dr.Henk Timmerman)
ProfessorshipforMolecularDrugResearchatthe Heinrich-Heine-UniversitätDüsseldorfuntilhisretirement onJuly9,2012
Editorofthebookseries“MethodsandPrinciplesin MedicinalChemistry,”Wiley-VCH,Weinheim,togetherwith HugoKubinyiandHenkTimmerman(andsince2001with GerdFolkers)
Since2001 RegionaleditorofMini-ReviewsinMedicinalChemistry
Since2005 EditorialboardmemberofMedicinalChemistryandCurrent Computer-AidedDrugDesign
October–November2011
VisitingprofessorattheSchoolofPharmaceuticalSciences, UniversityofGeneva,UniversityofLausanne,Switzerland
Hisworkastheserialeditorofhisbookserieswillperpetuatehismemoryinthe pharmaceuticalcommunityworldwide.Hisbookserieshasnowestablisheditself asaninternationallyrecognizedstandard,andmillionsofscientistswillcontinueto seehisnameandappreciatehisworksinthefuture.
WiththedeathofRaimundweloseapartofthespiritofthebookseries,which isverydifficulttogetover.Buthisfootprintonthevolumespublishedsofarwillbe documentedforeverandthusremainavaluablepartofscholarship.
1http://www.raimund-mannhold.de/curriculum-vitae/
xx RaimundMannhold–APersonalObituaryfromtheSeriesEditors
DearRaimund,inadditiontoyourcontent-relatedinput,wewillalsomissthe extremelypreciseplanningforyourbelovedbookseries.
Wepromisetocontinueyourandnowourbookseries“MethodsandPrinciples inMedicinalChemistry”inyourspirit,evenbeyondvolume100.
Withdeepsadness,butfilledwiththethoughtofcarryingyourspiriton,
Bonn,Porto,andAachen,July2023
Christa,Jörg,andHelmut