3D QSAR in Drug Design: Volume 1: Theory Methods and Applications

Hugo Kubinyi

Springer Science & Business Media, Dec 31, 1993 - Medical - 759 pages

Progress in medicinal chemistry and in drug design depends on our ability to understand the interactions of drugs with their biological targets. Classical QSAR studies describe biological activity in terms of physicochemical properties of substituents in certain positions of the drug molecules.
The purpose of this book is twofold: On the one hand, both the novice and the experienced user will be introduced to the theory and application of 3D QSAR analyses, and on the other, a comprehensive overview of the scope and limitations of these methods is given. The detailed discussion of the present state of the art should enable scientists to further develop and improve these powerful new tools.
The greater part of the book is dedicated to the theoretical background of 3D QSAR and to a discussion of CoMFA applications. In addition, various other 3D QSAR approaches and some CoMFA-related methods are described in detail. Thus, the book should be valuable for medicinal, agricultural and theoretical chemists, biochemists and biologists, as well as for other scientists interested in drug design. Its content, starting at a very elementary level and proceeding to the latest methodological results, the strengths and limitations of 3D QSAR approaches, makes the book also appropriate as a text for teaching and for graduate student courses.

Contents

• An Introduction: 3
• DrugReceptor Interactions: 13
• Generation and Use in 3D Searching: 41
• BindingSite Modeling of Unknown Receptors: 80
• Pharmacophore Identification: 117
• ComputerAssisted Pharmacophore Identification: 137
• Molecular Similarity: 150
• Structural Alignment of Molecules: 173
• Molecular Superposition for Rational Drug Design: 200
• Multiple Binding Modes: 226
• QSAR and Molecular Graphics: 257
• Advances in Molecular Shape Analysis: 276
• MTD and Hyperstructure Approaches: 305
• Binding Site Models: 318
• Minireceptors and Pseudoreceptors: 334
• Molecular Modelling of G ProteinCoupled Receptors: 353
• Steroid Receptor Models: 371
• Ligand Design: 384
• ThreeDimensional Receptor Modelling Using Distance Geometry and Voronoi Polyhedra: 407
• The Hypothetical ActiveSite Lattice: 429
• The Developing Practice of Comparative Molecular Field Analysis: 441
• Molecular Interaction Fields: 484
• Hydrophobic Fields: 504
• PLS Partial LeastSquares Projections to Latent Structures: 521
• Variable Selection in PLS Analysis: 549
• Series Design: 565
• Scope and Limitations: 581
• Comparison of Classical and 3D QSAR: 617
• A Case Study: 641
• Applications of CoMFA and Related 3D QSAR Approaches: 659
• CoMFADerived Substituent Descriptors for StructureProperty Correlations: 695
• Recommendations for CoMFA Studies and 3D QSAR Publications: 709
• Practical Problems in PLS Analyses: 715
• Author Index: 729
• Subject Index: 731

Bibliographic information

• Title: 3D QSAR in Drug Design: Volume 1: Theory Methods and Applications; Volume 1 of 3D QSAR in drug design; Volume 9, Issue 14 of Perspectives in drug discovery and design; Volume 1 of Three-Dimensional Quantitative Structure Activity Relationships
• Editor: Hugo Kubinyi
• Edition: illustrated
• Publisher: Springer Science & Business Media, 1993
• ISBN: 9072199146, 9789072199140
• Length: 759 pages
• Subjects: Medical / Biochemistry; Medical / Pharmacology; Medical / Pharmacy; Science / Chemistry / Computational & Molecular Modeling; Science / Chemistry / General; Science / Chemistry / Physical & Theoretical