Details

De novo Molecular Design


De novo Molecular Design


1. Aufl.

von: Gisbert Schneider

147,99 €

Verlag: Wiley-VCH
Format: EPUB
Veröffentl.: 10.10.2013
ISBN/EAN: 9783527677030
Sprache: englisch
Anzahl Seiten: 576

DRM-geschütztes eBook, Sie benötigen z.B. Adobe Digital Editions und eine Adobe ID zum Lesen.

Beschreibungen

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.<br> <br> 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.<br> <br> 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.<br> <br> <br> From the content:<br> <br> * Reaction-driven de novo design<br> * Adaptive methods in molecular design<br> * Design of ligands against multitarget profiles<br> * Free energy methods in ligand design<br> * Fragment-based de novo design<br> * Automated design of focused and target family-oriented compound libraries<br> * Molecular de novo design by nature-inspired computing<br> * 3D QSAR approaches to de novo drug design<br> * Bioisosteres in de novo design<br> * De novo design of peptides, proteins and nucleic acid structures, including RNA aptamers<br> <br> and many more.<br>
Foreword<br> Preface<br> <br> DE NOVO DESIGN: FROM MODELS TO MOLECULES<br> Molecular Representation<br> The Molecular Design Cycle<br> Receptor-Ligand Interaction<br> Modeling Fitness Landscapes<br> Strategies for Compound Construction<br> Strategies for Compound Scoring<br> Flashback Forward: A Brief History of De Novo Drug Design<br> Conclusions<br> <br> COPING WITH COMPLEXITY IN MOLECULAR DESIGN<br> Introduction<br> A Simple Model of Molecular Interactions<br> Enhancements to the Simple Complexity Model<br> Enumerating and Sampling the Complexity of Chemical Space<br> Validation of the Complexity Model<br> Reductionism and Drug Design<br> Complexity and Information Content as a Factor in De Novo Design<br> Complexity of Thermodynamic Entropy and Drug Design<br> Complex Systems, Emergent Behavior, and Molecular Design <br> <br> THE HUMAN POCKETOME<br> Predicted Pockets<br> Compilation of the Validated Human Pocketome<br> Diversity and Redundancy of the Human Pocketome<br> Compound Activity Prediction by Ligand-Pocket Docking and Scoring<br> Pocketome-Derived 3D Chemical Fields as Activity Prediction Models<br> Clustering the Ligands by Function and Subpockets<br> Conclusions<br> <br> STRUCTURE-BASED DE NOVO DRUG DESIGN<br> Introduction<br> Current Progress in SBDND Methodologies<br> Recent Applications of Structure-Based De Novo Design<br> Perspectives and Conclusion<br> <br> DE NOVO DESIGN BY FRAGMENT GROWING AND DOCKING<br> Introduction<br> Case Study I: High-Throughput Screening with Dr Feils<br> Case Study II: Fragment-Based Drug Design with Dr Goode<br> Conclusion<br> <br> HIT AND LEAD IDENTIFICATION FROM FRAGMENTS<br> Introduction to FBDD<br> Fragment Library Design Incorporating Computational Methods<br> Fragment Screening<br> Fragment Prioritization for Optimization<br> Fragment Hit Expansion and Fragment Evolution<br> Fragment Merging Principles<br> Fragment Linking Principles<br> Fragment-Assisted Drug Discovery (FADD)<br> Conclusion<br> <br> PHARMACOPHORE-BASED DE NOVO DESIGN<br> Introduction<br> A Summary of the Algorithms of PhDD v1.0<br> An Introduction to the Modifications in the Updated Version of PhDD (v2.0)<br> Validation of PhDD<br> Concluding Remarks<br> <br> 3D-QSAR APPROACHES TO DE NOVO DRUG DESIGN<br> Introduction<br> Current Methods<br> Leapfrog<br> Recent Advances<br> Conclusions<br> <br> LIGAND-BASED MOLECULAR DESIGN USING PSEUDORECEPTORS<br> Introduction<br> Pseudoreceptor Algorithms<br> Successful Applications Overview<br> Conclusions<br> <br> REACTION-DRIVEN DE NOVO DESIGN: A KEYSTONE FOR AUTOMATED DESIGN OF TARGET FAMILY-ORIENTED LIBRARIES<br> Introduction<br> Reaction-Driven Design: Tackling the Problem of Synthetic Feasibility<br> Successful Applications of Reaction-Driven De Novo Design<br> Reaction-Driven Design of Chemical Libraries Addressing Target Families<br> Conclusions<br> <br> MULTIOBJECTIVE DE NOVO DESIGN OF SYNTHETICALLY ACCESSIBLE COUMPOUNDS<br> Introduction<br> Design of Synthetically Accessible Compounds<br> Synthetic Accessibility Using Reaction Vectors<br> De Novo Design Using Evolutionary Algorithms<br> Conclusions<br> <br> DE NOVO DESIGN OF LIGANDS AGAINST MULTITARGET PROFILES<br> Introduction<br> Automating the Creativity of Ligand Design<br> Evolutionary Algorithm<br> Experimental Validation<br> Reducing Antitarget Activity<br> Optimizing D4 Receptor Potency<br> Designing Novel Ligands to a Defined Profile<br> Conclusion<br> <br> CONSTRUCTION OF DRUG-LIKE COMPOUNDS BY MARKOV CHAINS<br> Introduction<br> FOG Algorithm and Library Generation<br> Applications<br> Conclusion<br> <br> COPING WITH COMBINATORIAL SPACE IN MOLECULAR DESIGN<br> Introduction<br> Chemical Space<br> Combinatorial Space<br> Visualization<br> Conclusion<br> <br> FRAGMENT-BASED DESIGN OF FOCUSED COMPOUND LIBRARIES<br> Introduction<br> General Workflow<br> Fragment Space<br> Query<br> FTrees Fragment Space Search<br> Scaffold Selection<br> Design of Focused Libraries<br> Application Example<br> Summary and Conclusions<br> <br> FREE ENERGY METHODS IN LIGAND DESIGN<br> Free Energy (FE) Methods in Lead Optimization (LO)<br> The Variety of In Silico Binding Affinity Methods<br> The Choice of a Method for Calculating Binding FE<br> Experimental Data<br> Current Issues <br> Practical Examples<br> Miscellaneous Issues<br> Best Practices<br> Conclusions and Outlook<br> <br> BIOISOSTERES IN DE NOVO DESIGN<br> Introduction<br> History of Isosterism and Bioisosterism<br> Methods for Bioisosteric Replacement<br> Exemplar Applications<br> Conclusions<br> <br> PEPTIDE DESIGN BY NATURE-INSPIRED ALGORITHMS<br> Template-Based Design<br> Nature-Inspired Optimization<br> Worked Example: De Novo Design of MHC-I Binding Peptides by Ant Colony Optimization<br> Chemical Modification<br> Conclusions and Outlook<br> <br> DE NOVO COMPUTATIONAL PROTEIN DESIGN<br> Introduction<br> Elements of Computational Protein Design<br> Efforts in Theoretically Guided Protein Design<br> Conclusion<br> <br> DE NOVO DESIGN OF NUCLEIC ACID STRUCTURES<br> Introduction<br> DNA-Branched Structures<br> Scaffolded DNA Origami Design<br> Alternative DNA Designs: Between Junctions and Origami<br> Conclusions<br> <br> RNA APTAMER DESIGN<br> Aptamers and Design<br> Riboswitches and Aptamers<br> SELEX<br> Speeding Up SELEX by Computational Methods<br> Structures and Probing Methods<br> Functional Analyses (In Vitro and In Vivo)<br> Problems<br> Future Perspectives<br> <br> Index<br>
Gisbert Schneider is full professor of computer-assisted drug design at ETH Zurich, 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.
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.<br> <br> 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.<br> <br> 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.<br> <br> <br> From the content:<br> <br> * Reaction-driven de novo design<br> * Adaptive methods in molecular design<br> * Design of ligands against multitarget profiles<br> * Free energy methods in ligand design<br> * Fragment-based de novo design<br> * Automated design of focused and target family-oriented compound libraries<br> * Molecular de novo design by nature-inspired computing<br> * 3D QSAR approaches to de novo drug design<br> * Bioisosteres in de novo design<br> * De novo design of peptides, proteins and nucleic acid structures, including RNA aptamers<br> <br> and many more.<br>

Diese Produkte könnten Sie auch interessieren:

Hot-Melt Extrusion
Hot-Melt Extrusion
von: Dennis Douroumis
PDF ebook
126,99 €
Hot-Melt Extrusion
Hot-Melt Extrusion
von: Dennis Douroumis
EPUB ebook
126,99 €
Kunststoffe
Kunststoffe
von: Wilhelm Keim
PDF ebook
99,99 €