Virtual Screening for Bioactive Molecules

Dr. Hans-Joachim Bцhm, Dr. Gisbert Schneider3-527-30153-4

Recent progress in high-throughput screening, combinatorial chemistry and molecular biology has radically changed the approach to drug discovery in the pharmaceutical industry. New challenges in synthesis result in new analytical methods. At present, typically 100,000 to one million molecules have to be tested within a short period and, therefore, highly effective screening methods are necessary for today’s researchers – preparing and characterizing one compound after another belongs to the past. Intelligent, computer-based search agents are needed and “virtual screening” provides solutions to many problems. Such screening comprises innovative computational techniques designed to turn raw data into valuable chemical information and to assist in extracting the relevant molecular features.

This handbook is unique in bringing together the various efforts in the field of virtual screening to provide the necessary methodological framework for more effective research. Leading experts give a thorough introduction to the state of the art along with a critical assessment of both successful applications and drawbacks. The information collated here will be indispensable for experienced scientists, as well as novices, working in medicinal chemistry and related disciplines.

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Table of contents :
Cover……Page 1
Virtual Screening for Bioactive Molecules……Page 2
Methods and Principles in Medicinal Chemistry……Page 3
Copyright……Page 5
Preface……Page 6
A Personal Foreword……Page 7
Contents……Page 8
List of Contributors……Page 14
Why is Virtual Screening Important?……Page 17
1 High-Throughput Screening and Virtual Screening: Entry Points to Drug Discovery……Page 19
2 Library Filtering Systems and Prediction of Drug-Like Properties……Page 33
3 Prediction of Physicochemical Properties……Page 51
4 Descriptor-Based Similarity Measures for Screening Chemical Databases……Page 77
5 Modelling Structure-Activity Relationships……Page 99
6 Database Profiling by Neural Networks……Page 135
7 Pharmacophore Pattern Application in Virtual Screening, Library Design and QSAR……Page 148
8 Evolutionary Molecular Design in Virtual Fitness Landscapes……Page 177
9 Practical Approaches to Evolutionary Design……Page 203
10 Understanding Receptor-Ligand Interactions as a Prerequisite for – Virtual Screening……Page 222
11 Structure-Based Library Design……Page 243
12 The Measurement of Molecular Diversity……Page 279
Index……Page 315
Back Cover……Page 322