De novo Molecular Design

Foreword
Preface
 
DE NOVO DESIGN: FROM MODELS TO MOLECULES
Molecular Representation
The Molecular Design Cycle
Receptor-Ligand Interaction
Modeling Fitness Landscapes
Strategies for Compound Construction
Strategies for Compound Scoring
Flashback Forward: A Brief History of De Novo Drug Design
Conclusions
 
COPING WITH COMPLEXITY IN MOLECULAR DESIGN
Introduction
A Simple Model of Molecular Interactions
Enhancements to the Simple Complexity Model
Enumerating and Sampling the Complexity of Chemical Space
Validation of the Complexity Model
Reductionism and Drug Design
Complexity and Information Content as a Factor in De Novo Design
Complexity of Thermodynamic Entropy and Drug Design
Complex Systems, Emergent Behavior, and Molecular Design
 
THE HUMAN POCKETOME
Predicted Pockets
Compilation of the Validated Human Pocketome
Diversity and Redundancy of the Human Pocketome
Compound Activity Prediction by Ligand-Pocket Docking and Scoring
Pocketome-Derived 3D Chemical Fields as Activity Prediction Models
Clustering the Ligands by Function and Subpockets
Conclusions
 
STRUCTURE-BASED DE NOVO DRUG DESIGN
Introduction
Current Progress in SBDND Methodologies
Recent Applications of Structure-Based De Novo Design
Perspectives and Conclusion
 
DE NOVO DESIGN BY FRAGMENT GROWING AND DOCKING
Introduction
Case Study I: High-Throughput Screening with Dr Feils
Case Study II: Fragment-Based Drug Design with Dr Goode
Conclusion
 
HIT AND LEAD IDENTIFICATION FROM FRAGMENTS
Introduction to FBDD
Fragment Library Design Incorporating Computational Methods
Fragment Screening
Fragment Prioritization for Optimization
Fragment Hit Expansion and Fragment Evolution
Fragment Merging Principles
Fragment Linking Principles
Fragment-Assisted Drug Discovery (FADD)
Conclusion
 
PHARMACOPHORE-BASED DE NOVO DESIGN
Introduction
A Summary of the Algorithms of PhDD v1.0
An Introduction to the Modifications in the

Gisbert Schneider is full professor of computer-assisted drug design at ETH Zürich, Switzerland. He studied biochemistry and computer science at the Free University of Berlin, Germany. After several international postdoctoral research activities he joined F. Hoffmann-La Roche Pharmaceuticals in Basel, Switzerland, where he headed the cheminformatics group. From 2002-2009 he was full professor of cheminformatics and bioinformatics (Beilstein Endowed Chair) at Goethe-University Frankfurt, Germany. Professor Schneider coined the terms "scaffold-hopping" and "frequent hitter" in drug design. His research activities concentrate on method development for adaptive molecular design and their tight integration with innovative chemical and biophysical techniques in drug discovery.