Chemogenomics and Chemical Genetics : A User's Introduction for Biologists, Chemists and Informaticians

Biological and chemical sciences have undergone an unprecedented transformation, reflected by the huge use of parallel and automated technologies in key fields such as genome sequencing, DNA chips, nanoscale functional biology or combinatorial chemistry. It is now possible to generate and store from tens of thousands to millions of new small molecules, based on enhanced chemical synthesis strategies. Automated screening of small molecules is one of the technologies that has revolutionized biology, first developed for the pharmaceutical industry and recently introduced in academic laboratories. High-throughput and high-content screening allow the identification of bioactive compounds in collections of molecules (chemical libraries), being effective on biological targets defined at various organisational scales, from proteins to cells to complete organisms. These bioactive molecules can be therapeutic drug candidates, molecules for biotech, diagnostic or agronomic applications, or tools for basic research. Handling a large number of biological (genomic and post-genomic), chemical and experimental information, screening approaches cannot be envisaged without any electronic storage and mathematical treatment of the data. “Chemogenomics and Chemical Genetics" is an introductory manual presenting methods and concepts making up the basis for this recent discipline. This book is dedicated to biologists, chemists and computer scientist beginners. It is organized in brief, illustrated chapters with practical examples. Clear definitions of billogical, chemical and IT concepts are given in a glossary section to help readers who are not familiar with one of these disciplines. "Chemogenomics and Chemical Genetics" should therefore be helpful for students (from Bachelor's degree level), technological platform engineers, and researchers in biology, chemistry, bioinformatics, cheminformatics, both in biotech and academic laboratories. Biological And Chemical Sciences Have Undergone An Unprecedented Transformation, Reflected By The Huge Use Of Parallel And Automated Technologies In Key Fields Such As Genome Sequencing, Dna Chips, Nanoscale Functional Biology Or Combinatorial Chemistry. It Is Now Possible To Generate And Store From Tens Of Thousands To Millions Of New Small Molecules, Based On Enhanced Chemical Synthesis Strategies. Automated Screening Of Small Molecules Is One Of The Technologies That Has Revolutionized Biology, First Developed For The Pharmaceutical Industry And Recently Introduced In Academic Laboratories. High-throughput And High-content Screening Allow The Identification Of Bioactive Compounds In Collections Of Molecules (chemical Libraries), Being Effective On Biological Targets Defined At Various Organisational Scales, From Proteins To Cells To Complete Organisms. These Bioactive Molecules Can Be Therapeutic Drug Candidates, Molecules For Biotech, Diagnostic Or Agronomic Applications, Or Tools For Basic Research. Handling A Large Number Of Biological (genomic And Post-genomic), Chemical And Experimental Information, Screening Approaches Cannot Be Envisaged Without Any Electronic Storage And Mathematical Treatment Of The Data. “chemogenomics And Chemical Genetics” Is An Introductory Manual Presenting Methods And Concepts Making Up The Basis For This Recent Discipline. This Book Is Dedicated To Biologists, Chemists And Computer Scientist Beginners. It Is Organized In Brief, Illustrated Chapters With Practical Examples. Clear Definitions Of Biological, Chemical And It Concepts Are Given In A Glossary Section To Help Readers Who Are Not Familiar With One Of These Disciplines. Chemogenomics And Chemical Genetics Should Therefore Be Helpful For Students (from Bachelor's Degree Level), Technological Platform Engineers, And Researchers In Biology, Chemistry, Bioinformatics, Cheminformatics, Both In Biotech And Academic Laboratories. Front Matter....Pages i-xvi Front Matter....Pages 5-5 The pharmacological screening process: the small molecule, the biological Screen, the robot, the signal and the information....Pages 7-21 Collections of molecules for screening: example of the french national chemical library....Pages 23-28 The miniaturised biological assay: constraints and limitations....Pages 29-42 The signal: statistical aspects, normalisation, elementary analysis....Pages 43-53 Measuring Bioactivity: KI, IC50 and EC50....Pages 55-65 Modelling the pharmacological screening: controlling the processes and the chemical, biological and experimental information....Pages 67-78 Quality procedures in automated screening....Pages 79-84 Front Matter....Pages 85-85 Phenotypic Screening with Cells and Forward Chemical Genetics Strategies....Pages 87-102 High-Content Screening in Forward (Phenotypic Screening with Organisms) and Reverse (Structural Screening by NMR ) Chemical Genetics....Pages 103-112 Some Principles of Diversity-Oriented Synthesis....Pages 113-131 Front Matter....Pages 133-133 Molecular Descriptors and Similarity Indices....Pages 135-151 Molecular Lipophilicity: A Predominant Descriptor for QSAR....Pages 153-170 Annotation and classification of chemical space in chemogenomics....Pages 171-183 Annotation and classification of biological space in chemogenomics....Pages 185-195 Machine learning and screening data....Pages 197-212 Virtual screening by molecular docking....Pages 213-224 Front Matter....Pages 225-225 Biodiversity as a source of small molecules for pharmacological screening: libraries of plant extracts....Pages 227-240 Back Matter....Pages 241-256