This handbook is the first to address the practical aspects of this novel method. It provides a complete overview of the field and progresses from general considerations to real life scenarios in drug discovery research.
Starting with an introductory historical overview, the authors move on to discuss ligand-based approaches, including 3D pharmacophores and 4D QSAR, as well as the concept and application of pseudoreceptors. The next section on structure-based approaches includes pharmcophores from ligand-protein complexes, FLIP and 3D protein-ligand binding interactions. The whole is rounded off with a complete section devoted to applications and examples, including modeling of ADME properties.
With its critical evaluation of pharmacophore-based strategies, this book represents a valuable aid for project leaders and decision-makers in the pharmaceutical industry, as well as pharmacologists, and medicinal and chemists.
Chapter 1 Pharmacophores: Historical Perspective and Viewpoint from a Medicinal Chemist (pages 1–13): Camille G. Wermuth
Chapter 2 Pharmacophore Model Generation Software Tools (pages 15–47): Konstantin Poptodorov, Tien Luu and Remy D. Hoffmann
Chapter 3 Alignment?Free Pharmacophore Patterns – A Correlation?Vector Approach (pages 49–79): Steffen Renner, Uli Fechner and Gisbert Schneider
Chapter 4 Feature Trees: Theory and Applications from Large?scale Virtual Screening to Data Analysis (pages 81–116): Matthias Rarey, Sally Hindle, Patrick Maa?, Gunther Metz, Christian Rummey and Marc Zimmermann
Chapter 5 Concept and Applications of Pseudoreceptors (pages 117–130): Klaus?Jurgen Schleifer
Chapter 6 Pharmacophores from Macromolecular Complexes with LigandScout (pages 131–150): Gerhard Wolber and Robert Kosara
Chapter 7 GRID?based Pharmacophore Models: Concept and Application Examples (pages 151–170): Francesco Ortuso, Stefano Alcaro and Thierry Langer
Chapter 8 “Hot Spot” Analysis of Protein?binding Sites as a Prerequisite for Structure?based Virtual Screening and Lead Optimization (pages 171–192): Ruth Brenk and Gerhard Klebe
Chapter 9 Application of Pharmacophore Fingerprints to Structure?Based Design and Data Mining (pages 193–206): Prabha Karnachi and Amit Kulkarni
Chapter 10 SIFt: Analysis, Organization and Database Mining for Protein?Inhibitor Complexes. Application to Protein Kinase Inhibitors (pages 207–222): Juswinder Singh, Zhan Deng and Claudio Chuaqui
Chapter 11 Application of Structure?Based Alignment Methods for 3D QSAR Analyses (pages 223–249): Wolfgang Sippl
Chapter 12 Application of Pharmacophore Models in Medicinal Chemistry (pages 251–282): Fabrizio Manetti, Maurizio Botta and Andrea Tafi
Chapter 13 GPCR Anti?Target Modeling: Pharmacophore Models to Avoid GPCR?Mediated Side?Effects (pages 283–297): Thomas Klabunde
Chapter 14 Pharmacophores for Human ADME/Tox?Related Proteins (pages 299–324): Cheng Chang and Sean Ekins
Chapter 15 Are You Sure You Have a Good Model? (pages 325–364): Nicolas Triballeau, Hugues?Olivier Bertrand and Francine Acher