Combinatorial Library Design and Evaluation - Principles, Software Tools and Applications in Drug Discovery

648 pages, Illustrated  ISBN 0824704878      £125.00

This book covers recent developments in rational drug discovery and combinatorial library design with contributions from 50 leading scientists in academia and industry who offer in-depth coverage of basic principles, design strategies, methodologies, software tools and algorithm, and applications. It outlines fundamentals of pharmacophore modelling and 3D Quantitative Structure-Activity Relationships (QSAR), classical QSAR, and target protein structure-based design methods. It will be of interest to organic, medicinal, pharmaceutical, computational, protein, and peptide chemists and biochemists; pharmacists; pharmacologists and molecular biologists as well as advanced students in these disciplines.

Contents

Introduction - library design concepts and implementation strategies.

Part 1 Design principles: fundamentals of pharmacophore modelling for combinatorial chemistry;
pharmacophore modelling for combinatorial chemistry;
quantitative structure-activity relationships (QSAR) - versatile tool in drug design;
quantitative structure-activity relationships (QSAR) - a review of 3D QSAR;
binding energy landscapes of ligand-protein complexes and molecular docking - principles, methods and validation experiments;
fast continuum electrostatics methods for structure-based ligand design;
quo vadis, scoring functions? toward an integrated pharmacokinetic and binding affinity prediction framework.

Part 2 Current methods and software tools:
knowledge-based approaches for the design of small molecule libraries for drug discovery;
drug-likeness profiles of chemical libraries;
tools for designing diverse, drug-like, cost-effective combinatorial libraries;
relative and asbolute diversity analysis of combinatorial libraries;
rational combinatorial library design and database mining using inverse QSAR approach;
dissimilarity-based compound selection for library design;
pharmacore-based approaches to combinatorial library design;
high throughput conformational sampling and fuzzy similarity metrics - a novel approach to similarity searching and focused combinatorial library design and its role in the drug discovery laboratory.

Part 3 Applications: applications of cell-based diversity methods to combinatorial library design; structure based combinatorial library design and screening - applications of the multiple copy simultaneous search method;
genetic algorithm-directed lead generation;
enhancement of the drug discovery process by integration of structure-based drug design and combinatorial synthesis;
design of structrural combinatorial libraries that mimic biological motifs.