Open Access Databases and Datasets for Drug Discovery -

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Résumé :

Series Editors Preface xiii

Raimund Mannhold - A Personal Obituary from the Series Editors xvii

A Personal Foreword xxi

1 Open Access Databases and Datasets for Computer-Aided Drug Design. A Short List Used in the Molecular Modelling Group of the SIB 1
Antoine Daina, Mar?a Jos? Ojeda-Montes, Maiia E. Bragina, Alessandro Cuozzo, Ute F. R?hrig, Marta A.S. Perez, and Vincent Zoete

References 30

Part I Small Molecules 39

2 PubChem: A Large-Scale Public Chemical Database for Drug Discovery 41
Sunghwan Kim and Evan E. Bolton

2.1 Introduction 41

2.2 Data Content and Organization 42

2.3 Tools and Services 45

2.3.1 PubChem Search 45

2.3.2 Summary Pages 48

2.3.3 Literature Knowledge Panel 49

2.3.4 2D and 3D Neighbors 50

2.3.5 Classification Browser 51

2.3.6 Identifier Exchange Service 52

2.3.7 Programmatic Access 52

2.3.8 PubChem FTP Site and PubChemRDF 53

2.4 Drug- and Lead-Likeness of PubChem Compounds 54

2.5 Bioactivity Data in PubChem 56

2.6 Comparison with Other Databases 57

2.7 Use of PubChem Data for Drug Discovery 58

2.8 Summary 59

Acknowledgments 60

References 60

3 DrugBank Online: A How-to Guide 67
Christen M. Klinger, Jordan Cox, Denise So, Teira Stauth, Michael Wilson, Alex Wilson, and Craig Knox

3.1 Introduction 67

3.2 DrugBank 68

3.2.1 Overview of DrugBank 68

3.2.2 DrugBank Datasets 69

3.2.2.1 Drug Cards: An Overview and Navigation Guide 70

3.2.2.2 Identification 70

3.2.2.3 Pharmacology 71

3.2.2.4 Categories 73

3.2.2.5 Properties 73

3.2.2.6 Targets, Enzymes, Carriers, and Transporters 73

3.2.2.7 References 77

3.3 Protocols 77

3.3.1 General Workflows 77

3.3.1.1 Using DrugBank Online's Search Functionality 77

3.3.1.2 Using DrugBank Online's Advanced Search Functionality 80

3.3.1.3 Browsing Drugs Using DrugBank Online's Drug Categories 83

3.3.2 Identifying Chemicals and Relevant Sequences 86

3.3.2.1 Searching Using Chemical Structure Search 86

3.3.2.2 Using Sequence Search to Find Similar Targets 89

3.3.3 Extracting DrugBank Datasets for ml 93

3.4 Research Using DrugBank 94

3.5 Discussion and Conclusions 95

References 96

4 Bioisosteric Replacement for Drug Discovery Supported by the SwissBioisostere Database 101
Antoine Daina, Alessandro Cuozzo, Marta A.S. Perez, and Vincent Zoete

4.1 Introduction 101

4.1.1 Concept of Isosterism and Bioisosterism 101

4.1.2 Classical vs. Non-classical Bioisostere and Further Molecular Replacements 102

4.1.3 Bioisosteric Replacement in Drug Discovery 105

4.2 Construction and Dissemination of SwissBioisostere 106

4.2.1 Intention and Requirements 106

4.2.2 Bioactivity Data 107

4.2.3 Nonsupervised Matched Molecular Pair Analysis 108

4.2.4 Database 108

4.2.5 Web Interface 109

4.3 Content of SwissBioisostere 111

4.3.1 Global Content 111

4.3.2 Biological and Chemical Contexts 112

4.3.3 Fragment Shape Diversity 113

4.4 Usage of SwissBioisostere 115

4.4.1 Website Usage 115

4.4.2 Most Frequent Requests 117

4.4.3 Examples Related to Drug Discovery 117

4.4.3.1 Use Cases 117

4.4.3.2 Replacing Unwanted Chemical Groups 118

4.4.3.3 Optimization of Passive Absorption and Blood-Brain Barrier Diffusion 122

4.4.3.4 Reduction of Flexibility 124

4.4.3.5 Reduction of Aromaticity/Escape from Flatland 128

4.5 Conclusive Remarks 133