De novo Molecular Design

Systematically examining current methods and strategies, this ready reference covers a wide range of molecular structures, from organic–chemical drugs to peptides, Proteins and nucleic acids, in line with emerging new drug classes derived from biomacromolecules. A leader in the field and one of the pioneers of this young discipline has assembled here the most prominent experts from across the world to provide first–hand knowledge. While most of their methods and examples come from the area of pharmaceutical discovery and development, the approaches are equally applicable for chemical probes and diagnostics, pesticides, and any other molecule designed to interact with a biological system. Numerous images and screenshots illustrate the many examples and method descriptions. With its broad and balanced coverage, this will be the firststop resource not only for medicinal chemists, biochemists and biotechnologists, but equally for bioinformaticians and molecular designers for many years to come. From the content: ∗ Reaction–driven de novo design ∗ Adaptive methods in molecular design ∗ Design of ligands against multitarget profiles ∗ Free energy methods in ligand design ∗ Fragment–based de novo design ∗ Automated design of focused and target family–oriented compound libraries ∗ Molecular de novo design by nature–inspired computing ∗ 3D QSAR approaches to de novo drug design ∗ Bioisosteres in de novo design ∗ De novo design of peptides, proteins and nucleic acid structures, including RNA aptamers and many more.

De novo design: from models to molecules Structure–based molecular de novo design Computational Fragment–Based Drug Design De novo design by fragment growing and docking Reaction–based de novo design Virtual organic synthesis for de novo compound construction Pharmacophore–based de novo design Ligand–based molecular design using pseudoreceptors Shape–based approaches to de novo drug design Multi–dimensional de novo design of druglike compounds Polypharmacology–based de novo design Combinatorial molecular de novo design Fragment–based design of focused compound libraries Construction of druglike compounds by Markov chains Molecular design by fragment shuffling Ligand design by Free Energy Perturbation Bioisosteric replacements for de novo drug design Peptide design by nature–inspired computing Peptoid de novo design Designing proteins de novo De novo design of nucleic acid structure

Gisbert Schneider is full professor of computer–assisted drug design at ETH Zürich, Switzerland. He studied biochemistry and computer science at the Free University of Berlin, Germany. After several international postdoctoral research activities he joined F. Hoffmann–La Roche Pharmaceuticals in Basel, Switzerland, where he headed the cheminformatics group. From 2002–2009 he was full professor of cheminformatics and bioinformatics (Beilstein Endowed Chair) at Goethe–University Frankfurt, Germany. Professor Schneider coined the terms "scaffold–hopping" and "frequent hitter" in drug design. His research activities concentrate on method development for adaptive molecular design and their tight integration with innovative chemical and biophysical techniques in drug discovery.