Structure-based drug discovery : an overview
Roderick E. Hubbard · 2006
Chapter 1: 3D Structure and the Drug Discovery Process 1: Introduction 2: The Drug Discovery Process 3: What is Structure-based Drug Discovery? 4: The Evolution of the Ideas of Structure-based Drug Discovery 5: What isn't in this Book 6: Concluding Remarks References Chapter 2: Structure Detemination - Crystallography for Structure-based Drug Design 1: What is X-ray Crystallography? 2: What is required to Produce a Crystal Structure? 3: Crystallisability of Proteins 4: How Does the X-ray Data Relate to the Electron Density? The Phase Problem 5: Electron Density Map Interpretation and Atomic Model of the Protein 6: Useful Crystallographic Therminology when Utilising Crystal Structures 7: The Structure Determination Process 8: Recent technological Advances 9: The Role of Crystal Structures in the Discovery Process 10: The Optimal SBDD System 11: The Impact of Structural Genomics 12: Producing a Biologically Relevant Structure 13: Phosphorylation 14: Balancing Solubility with Crystallisability 15: Engineering Solubility 16: Specific Crystal Packing Engineering 17: Engineering Stability 18: Use of Surrogate Proteins References Chapter 3: Molecular Modelling 1: Introduction 2: Methods 3: Applications 4: Conclusion References Chapter 4: Applications of NMR in Structure-based Drug Design 1: Introduction 2: Studying Ligand/Receptor Interactions by NMR 3: NMR in Structure-based Lead Optimization 4: Other Applications of NMR in SBDD 5: Conclusion and Outlook References Chapter 5: Fragment Screening - An Introduction 1: Introduction 2: The Concept of Drug Likeness 3: The Evolution of Lead-likeness and Fragment Screening 4: Finding Fragments by Screening 5: The Design of Fragment Screening Sets 6: Turning Fragment Hits into Leads 7:Summary References Chapter 6: Iterative Structure-based Screening of Virtual Chemical Libraries and Factor Xa: Finding the Orally Available Antithrombotic Candadate LY517717 1: Introduction 2: Morphology of the Factor Xa Active Site 3: Structure-based Library Design 4: Design Strategy for Factor Xa 5: Introducing Oral Availability 6: Non-basic S1 Series 7: Oral Antithrombotic Activity 8: Conclusion References Chapter 7: Anti-influenza Drugs from Sialidase Inhibitors 1: Introduction 2: Influenza Viruses 3: Early Attempts to Discover Neuraminidase Inhibitors 4: Neuraminidase Structure 5: Structure-based Discovery of Inhibitors 6: Retrospective Analyses of Inhibitor-binding 7: Laboratory Studies of Inhibitor Resistant Variants 8: Clinical Studies of Drug Resistance 9: Drug Profiles Conclusions References Chapter 8: Isoform Specificity: The Design of Estrogen Receptor- Selective Compounds 1: Introduction 2: Structure-based Design Methodology 3: The Design of Aryl Diphenolic Azoles as ER? Selective Agonists 4: Learning From and Moving Beyond the Genistein Scaffold 5: Evaluation of ER? Selective Compounds in Biological Assays Conclusions Acknowledgements References