Structural Bioinformatics, 2nd Edition

27

DOCKING METHODS, LIGAND DESIGN, AND VALIDATING DATA SETS IN THE STRUCTURAL GENOMICS ERA

Natasja Brooijmans

INTRODUCTION

Since the beginning of civilization, humans have searched for substances that can cure or alleviate the symptoms of disease. In the early stages, extracts from plants and animal parts were used to treat disease, and the discovery of such remedies was driven empirically. Starting in the early 1900s, drug discovery has increasingly focused on discovering and developing chemical entities that on their own have a desired pharmaceutical effect. Initially this was fueled by attempts to extract and identify the active component in extracts from natural products that were used. A number of developments, however, have resulted in the multidisciplinary science that drug discovery is today, including the traditional fields of chemistry and pharmacology, along with contributions from biochemistry, molecular biology, and biophysics. Increasingly, computational tools are used in the drug discovery process from target identification and validation to the designing of new molecules.

The discoveries of several different concepts played a pivotal role in the development of drug discovery as an industry. In the nineteenth century, Paul Ehrlich developed the idea that different parasites, microorganisms, and cancer cells have dissimilar chemoreceptors resulting in different susceptibility to dyes. He hypothesized that these differences can be exploited therapeutically (Ehrlich, ...