This volume explores the latest available wet-lab techniques and computational methods to study in-cell small-molecule behavior and interactions with their targets. The chapters in this book discuss topics such as disease-relevant models for chemical biology studies, target engagement using cellular thermal shift assay or bioluminescence resonance energy transfer; visualization of bio-active small molecules Raman microscopy; (phospho-)proteomics and transcriptomics for mode-of-action studies, CRISPR/Cas9-based chemogenomic profiling in mammalian cells; predicting drug interactions using computational approaches; comparison of compound-induced profiles using high-content imaging or cancer cell line panels and web-based tools for polypharmacology prediction. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Systems Chemical Biology: Methods and Protocols is a valuable resource for novice or expert scientists and researchers trying to initiate or continue their chemical biology studies at a systems level.

The transduction of signals from the extracellular space across the plasma membrane into the interior of cells and ultimately to the nucleus, where in - sponse to such external signals the transcription of the genetic code is inf- enced,belongs to the most fundamental and important events in the regulation of the life cycle of cells. During recent years several signal transduction cascades have been elucidated which regulate,for instance,the growth and the prolife- tion of organisms as diverse as mammals, flies, worms and yeast. The general picture which emerged from these investigations is that nature employs a c- bination of non-covalent ligand/protein and protein/protein interactions together with a set of covalent protein modifications to generate the signals and transduce them to their destinations. The ligands which are recognized may be low molecular weight compounds like lipids, inositol derivatives, steroids or microbial products like cyclosporin. They may be proteins like, for instance, growth factors or intracellular adaptor proteins which carry SH2 or SH3 domains, and they may be specific DNA stretches which are selectively rec- nized by transcription factors. These and other aspects of biological signal transduction provide an open and rewarding field for investigations by scientists from various different dis- plines of biology,medical research and chemistry working in academic research institutions or in industry.

The transduction of signals from the extracellular space across the plasma membrane into the interior of cells and ultimately to the nucleus, where in - sponse to such external signals the transcription of the genetic code is inf- enced,belongs to the most fundamental and important events in the regulation of the life cycle of cells. During recent years several signal transduction cascades have been elucidated which regulate,for instance,the growth and the prolife- tion of organisms as diverse as mammals, flies, worms and yeast. The general picture which emerged from these investigations is that nature employs a c- bination of non-covalent ligand/protein and protein/protein interactions together with a set of covalent protein modifications to generate the signals and transduce them to their destinations. The ligands which are recognized may be low molecular weight compounds like lipids, inositol derivatives, steroids or microbial products like cyclosporin. They may be proteins like, for instance, growth factors or intracellular adaptor proteins which carry SH2 or SH3 domains, and they may be specific DNA stretches which are selectively rec- nized by transcription factors. These and other aspects of biological signal transduction provide an open and rewarding field for investigations by scientists from various different dis- plines of biology,medical research and chemistry working in academic research institutions or in industry.

Based on the international workshop on 'Small Molecule - Protein Interactions' held in Berlin, April 24-26, 2002, researchers from industry and academic laboratories describe novel and efficient ways selecting promising new drug targets and developing small molecule inhibitors against them. The structure of the book corresponds to the different aspects of the drug discovery process. All chapters are written by leading experts in the field, who present and discuss the most recent state-of-the-art tools and techniques for the development of novel drugs. The value of the book lies in surveying and summarizing the approaches taken by different companies and institutions giving the reader a balanced view on the use of the latest techniques on the one hand and experience-based assistance in selecting appropriate tools for their own work on the other hand.