Searching for molecular solutions : empirical discovery and its future /
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| Author / Creator: | Dunn, Ian S. |
|---|---|
| Imprint: | Hoboken, N.J. : John Wiley & Sons, c2010. |
| Description: | xix, 458 p. : ill. ; 25 cm. |
| Language: | English |
| Subject: | |
| Format: | Print Book |
| URL for this record: | http://pi.lib.uchicago.edu/1001/cat/bib/7914505 |
Table of Contents:
- Acknowledgments
- Introduction
- 1. If It Works, It Works: Pragmatic Molecular Discovery
- Overview
- Three Ways of Discovery
- The Three Wise (Serendipitous) Men and Other Stories
- An Empirical Fable
- Productively Applying Empiricism
- Screening Versus Selection
- How to be a Librarian
- Demon-strating the Power of Empirical Screening and Selection
- Dreaming of Pandemonium: a Universal Molecular Space
- Modes of Molecular Discovery
- The Borderland of Rational Design
- 2. Empirical Miracles: Nature's Precedents for Empirical Solutions
- Overview
- Evolution Itself
- Evolution: Natural and Artificial
- To Opine on Design
- Natural Evolution at Work
- The Raw Materials: Diversity Enough and Time
- GOD from Mutation
- GOD from Recombination and Other Things
- A Sexual Interlude
- Doubling Up and Reassorting
- Lateral Thinking
- The Process: Old Ideas and Newer Wrinkles
- The Marks of Lamarck?
- Evolution by Order?
- Orderly Beginnings
- The Arrow of Complexity?
- Drivers of Complexity
- Complexity and Molecular Discovery
- Molecules of Evolution and Design Boundaries
- Evolving Proteins
- Enzymatic Bounty
- Combinatorial Catalysis and Its Helpers
- Enzymes to the Limit
- Absent by Irreducibility, or Lack of an Access Route?
- Food for Evolutionary Thought
- 3. Evolution's Gift: Natural Somatic Diversification and Molecular Design
- Overview
- Immune Systems: a Biological Fundamental
- The Selfish Scheme
- The Xenobiotic "Immune System" and Beyond
- Innately Selfish
- How to Shoot Moving Targets
- The Empirical Basis of the Adaptive Immune System
- The Evolved GOD of the Adaptive Immune System
- The T Cell Repertoire and Its Special GOD
- The Range and Utility of Adaptive Immunity
- Antibodies and Molecular Recognition in General
- Selfishness Revisited
- Antibody Libraries and Iterative Selection: Natural and Artificial
- Iteratively Speaking
- Such Selfish Systems Send Selfless Sermons: The Largesse of Immune Systems
- GOD in the Brain and Its Extensions
- Molecular Sensing
- A Bittersweet Worldview
- Smelling a Rat, and Many Other Things
- Multirecogmtion
- Messages in Biological Molecular Recognition and Empirical Design
- 4. Evolution While You Wait
- Overview
- Putting Evolution to Work
- Levels of Selectable Replicators
- The Scope and Implementation of Evolution as a Workhorse
- God in the Laboratory
- Mutations at Will
- Sex for Biotechnologists
- Artificial Evolution Becomes HOT
- Evolution on the Laboratory Bench
- Screen (Properly) and Ye Shall Find
- A Highly Rational Empirical Process
- Mutations and Libraries
- Crossing the Valley of the Shadow of Low Fitness: Journeys across Molecular Spaces
- Colorful Neutral Springboards
- Punctuating Sequence Space, Naturally or Otherwise
- The Power of Display
- Show Me Your Coat: Phage on Display
- Display Without Cells: Doing It In Vitro
- Making Compartments
- Test It, Replicate It, Evolve It
- 5. The Blind Protein Maker
- Overview
- Applying Natural Protein Evolution Principles
- Productively Playing with Enzymes
- Room for Improvement
- Tougher Enzymes
- Better Enzymes
- Altered and Novel Enzymes
- Enzymes from Scratch
- De Novo Protein Design the Empirical Way
- Return to the Fold
- Alphabets and Patterning
- Finding and Evolving Folds
- De Novo Enzymes
- Natural and Unnatural Acts
- Unnatural Insertions
- In Vitro opportunities
- New Codes in Vivo
- Unnatural Rewards and Limits
- 6. The Blind Shaper of Nucleic Acids
- Overview
- Functional Nucleic Acids and their Directed Evolution
- Early Days
- Protein-Free Enzymes
- Finding Functional RNAs
- Novel Ribozymes
- Ribozyme Replication and Other Things
- Comparisons with Proteins
- Aiming for Stability
- Recombination: Still Good for RNA?
- Folding in Two Worlds
- Working with the Ribozyme Repertoire
- Calling for Cofactors
- Alphabetic Acrobatics
- Angling for Aptamers with Aptitude
- DNA Can Do It Too
- Natural Aptamers and Riboswitches
- An Aptamerican Adventure
- Allosteric Ribozymes and Aptamers
- Payoffs from Functional Nucleic Acids
- Aptamer Tools: Better than Antibodies?
- Moving Aptamers Toward the Clinic
- Extending the Functional Range of Nucleic Acids
- Extended Alphabets
- The Virtual Molecular Museum
- Altered Backbones
- The Best of Both Worlds?
- 7. Evolving and Creating Recognition Molecules
- Overview
- The Immune System in a Bottle and on a Leash
- New Wrinkles on the Old Way to Antibodies
- Antibodies and Libraries
- The GOD of Small Things: Minimizing Antibodies
- Antibodies as Catalysts
- Alternatives to Antibodies
- Other Protein Scaffolds for Molecular Recognition
- Finding and Designing Proteins for Diversification
- Molecular Imprinting: Making its Mark
- Imprinting of Macromolecules
- Comparing Recognition Alternatives
- Generalizing to Foldamers
- 8. Molecules Small and Large
- Overview
- As Small as Possible, but No Smaller
- Small and Natural, Small and Useful
- How to Find New Drugs
- Know Your NME
- Aiming in the Right Direction
- Druggable Struggles
- High-throughput Put Through High Loops
- Chemical Libraries and the GOD of Small Molecules
- Generalities and the Natural Approach
- Make Your Own Library
- Frag-mental Inspiration
- Self-Assembling Molecular Combinatorics
- Codes for Small Molecules
- Tag Team Technology: Encoded Combinatorial Chemistry
- Marrying Chemistry and Biology with Tags
- An Evolutionary Analogy
- From Small to Large and Back Again
- 9. An Empirical-Rational Loop Forwards
- Overview
- Approaching Rational Design
- Scope of Rational Design
- Pathways to Rational Design
- Quantum Chemistry and Rational Design
- Small Molecules the Rational Way
- Virtual Virtues
- The De Novo Ultimate?
- Proteins by the Book
- Getting Folding Right
- Making Rational Predictions
- Making Rational Proteins
- Designer Nucleic Acids
- Systems, Pathways, and Networks
- 10. Exploring the Limits
- Overview
- The Limits of Rational Design
- Rational Design and Determinism
- Bootstrapping and Interplay
- Reverse-engineering Biocomplexity for Design Insights
- Time, Knowledge, and Molecules
- Outer Boundaries
- Patterns for the Future
- Primordial Alphabet Soup
- On Molecular Translations
- Effectors and Replicators
- The Universal Power of Combinatorics
- A Kaleidoscopic View
- Glossary
- Bibliography
- References in Figure Legends
- Index
