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A comprehensive look at empirical approaches to molecular discovery, their relationships with rational design, and the future of both Empirical methods of discovery, along with serendipitous and rational design approaches, have played an important role in human history. Searching for Molecular Solutions compares empirical discovery strategies for biologically useful molecules with serendipitous discovery and rational design, while also considering the strengths and limitations of empirical pathways to molecular discovery. Logically arranged, this text examines the different modes of molecular…mehr
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A comprehensive look at empirical approaches to molecular discovery, their relationships with rational design, and the future of both Empirical methods of discovery, along with serendipitous and rational design approaches, have played an important role in human history. Searching for Molecular Solutions compares empirical discovery strategies for biologically useful molecules with serendipitous discovery and rational design, while also considering the strengths and limitations of empirical pathways to molecular discovery. Logically arranged, this text examines the different modes of molecular discovery, empha-sizing the historical and ongoing importance of empirical strategies. Along with a broad overview of the subject matter, Searching for Molecular Solutions explores: * The differing modes of molecular discovery * Biological precedents for evolutionary approaches * Directed evolutionary methods and related areas * Enzyme evolution and design * Functional nucleic acid discovery * Antibodies and other recognition molecules * General aspects of molecular recognition * Small molecule discovery approaches * Rational molecular design * The interplay between empirical and rational strategies and their ongoing roles in the future of molecular discovery Searching for Molecular Solutions covers several major areas of modern research, development, and practical applications of molecular sciences. This text offers empirical-rational principles of broad relevance to scientists, professionals, and students interested in general aspects of molecular discovery, as well as the thought processes behind experimental approaches.
Produktdetails
- Produktdetails
- Verlag: John Wiley & Sons
- Seitenzahl: 480
- Erscheinungstermin: 12. Januar 2010
- Englisch
- ISBN-13: 9780470551448
- Artikelnr.: 37296894
- Verlag: John Wiley & Sons
- Seitenzahl: 480
- Erscheinungstermin: 12. Januar 2010
- Englisch
- ISBN-13: 9780470551448
- Artikelnr.: 37296894
Ian S. Dunn, PhD, is the Director of Research at Cytocure, LLC, in Beverly, Massachusetts. In keeping with the scope of this book, he has a diverse background in immunology, cell and molecular biology, and biotechnology. His current research focuses on antigen gene regulation in melanoma cells.
Acknowledgments xi Introduction xiii 1 If It Works, It Works: Pragmatic Molecular Discovery 1 2 Empirical Miracles: Nature's Precedents for Empirical Solutions 22 3 Evolution's Gift: Natural Somatic Diversification and Molecular Design 61 4 Evolution While You Wait 103 5 The Blind Protein Maker 145 6 The Blind Shaper of Nucleic Acids 187 7 Evolving and Creating Recognition Molecules 234 8 Molecules Small and Large 275 9 An Empirical--Rational Loop Forwards 315 10 Exploring the Limits 343 Glossary 365 Bibliography 374 References in Figure Legends 440 Index 443
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. Mode 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. Multirecognition.
Messages in Biological Molecular Recognition and Empirical Design. 4
Evolution While You Wait. Overview. Putting Evolution to Work. Levels of
Selectable Replicators. The Score 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.
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. Mode 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. Multirecognition.
Messages in Biological Molecular Recognition and Empirical Design. 4
Evolution While You Wait. Overview. Putting Evolution to Work. Levels of
Selectable Replicators. The Score 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.
Acknowledgments xi Introduction xiii 1 If It Works, It Works: Pragmatic Molecular Discovery 1 2 Empirical Miracles: Nature's Precedents for Empirical Solutions 22 3 Evolution's Gift: Natural Somatic Diversification and Molecular Design 61 4 Evolution While You Wait 103 5 The Blind Protein Maker 145 6 The Blind Shaper of Nucleic Acids 187 7 Evolving and Creating Recognition Molecules 234 8 Molecules Small and Large 275 9 An Empirical--Rational Loop Forwards 315 10 Exploring the Limits 343 Glossary 365 Bibliography 374 References in Figure Legends 440 Index 443
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. Mode 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. Multirecognition.
Messages in Biological Molecular Recognition and Empirical Design. 4
Evolution While You Wait. Overview. Putting Evolution to Work. Levels of
Selectable Replicators. The Score 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.
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. Mode 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. Multirecognition.
Messages in Biological Molecular Recognition and Empirical Design. 4
Evolution While You Wait. Overview. Putting Evolution to Work. Levels of
Selectable Replicators. The Score 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.