Methods in Protein Design

Methods in Protein Design

1st Edition - February 14, 2013
This is the Latest Edition
  • Editor: Amy Keating
  • eBook ISBN: 9780123946294
  • Hardcover ISBN: 9780123942920

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Description

This new volume of Methods in Enzymology continues the legacy of this premier serial by containing quality chapters authored by leaders in the field. This volume covers methods in protein design and it has chapters on such topics as protein switch engineering by domain insertion, evolution based design of proteins, and computationally designed proteins.

Key Features

  • Continues the legacy of this premier serial with quality chapters authored by leaders in the field
  • Covers methods in protein design
  • Contains chapters with such topics as protein switch engineering by domain insertion, evolution-based design of proteins, and computationally designed proteins

Readership

Biochemists, biophysicists, molecular biologists, analytical chemists, and physiologists

Table of Contents

  • Contributors

    Preface

    Methods in Enzymology

    Chapter One. Computational Design of Novel Protein Binders and Experimental Affinity Maturation

    Abstract

    1 Introduction

    2 Computational Design of Binders Using Novel Scaffolds

    3 Target Selection

    4 Generating an Idealized Concept of the Hotspot

    5 Selecting Shape Complementary Scaffold Surfaces for Design

    6 Interface Design

    7 Yeast Cell-Surface Display as a Screening Method for Designed Binders

    8 Affinity Maturation

    9 What Works, What Fails, and What It Means

    Acknowledgments

    References

    Chapter Two. Mining Tertiary Structural Motifs for Assessment of Designability

    Abstract

    1 Introduction

    2 MaDCaT

    3 Quantifying Designability

    4 Further Developments

    5 Summary

    Acknowledgments

    References

    Chapter Three. Computational Methods for Controlling Binding Specificity

    Abstract

    1 Introduction

    2 Narrowing Down Binding Specificity

    3 Broadening Binding Specificity

    4 Summary

    Acknowledgments

    References

    Chapter Four. Flexible Backbone Sampling Methods to Model and Design Protein Alternative Conformations

    Abstract

    1 Introduction

    2 Rosetta Moves to Model Alternative Conformations in X-Ray Density

    3 Sequence Plasticity and Conformational Plasticity are Intertwined

    4 Future Challenges

    Acknowledgments

    References

    Chapter Five. OSPREY: Protein Design with Ensembles, Flexibility, and Provable Algorithms

    Abstract

    1 Introduction

    2 OSPREY Design Principles

    3 Applications of OSPREY

    4 Protein Design in OSPREY

    5 Example: Predicting Drug Resistance Mutations Using OSPREY

    6 Future Directions and Availability

    Acknowledgments

    References

    Chapter Six. Scientific Benchmarks for Guiding Macromolecular Energy Function Improvement

    Abstract

    1 Introduction

    2 Energy Function Model

    3 Feature Analysis

    4 Maximum Likelihood Parameter Estimation with optE

    5 Large-Scale Benchmarks

    6 Three Proposed Changes to the Rosetta Energy Function

    7 Conclusion

    Acknowledgments

    References

    Chapter Seven. Molecular Dynamics Simulations for the Ranking, Evaluation, and Refinement of Computationally Designed Proteins

    Abstract

    1 Introduction

    2 Inside-Out Computational Enzyme Design

    3 Filtering, Ranking, and Evaluation of Final Designs

    4 Discerning Active from Inactive Designs with MD

    5 MD Evaluation Examples

    6 MD Refinement Examples

    7 Molecular Dynamics Simulations: Preparation and Setup

    8 Conclusions

    Acknowledgments

    References

    Chapter Eight. Multistate Protein Design Using CLEVER and CLASSY

    Abstract

    1 Introduction: Accomplishments and Limitations of Structure-Based Design

    2 Theory

    3 Benefits Offered by Cluster Expansion in Protein Modeling and Design

    4 How to Run a Cluster Expansion with CLEVER 1.0

    5 GenSeqs

    6 CETrFILE

    7 CEEnergy

    8 Cluster Expansion Case Study

    9 Using Cluster Expansion with Integer Linear Programming

    10 CLASSY Applied to Multistate Design

    11 Conclusion

    Acknowledgments

    References

    Chapter Nine. Using Analyses of Amino Acid Coevolution to Understand Protein Structure and Function

    Abstract

    1 Introduction

    2 Predicting Specificity Determining Residues Using MI

    3 Concluding Remarks

    Acknowledgments

    References

    Chapter Ten. Evolution-Based Design of Proteins

    Abstract

    1 Introduction

    2 SCA: The Pattern of Evolutionary Constraint in Proteins

    3 SCA-Based Protein Design

    4 SCA-Based Parsing of Protein Stability and Function

    5 Future Monte Carlo Strategies for Exploring Sequence Space

    6 Conclusion

    Acknowledgments

    References

    Chapter Eleven. Protein Engineering and Stabilization from Sequence Statistics: Variation and Covariation Analysis

    Abstract

    1 Introduction

    2 Case Study: BPTI

    3 Acquiring an MSA

    4 Relative Entropies: Quantifying the Degree of Positional Variation

    5 Mutual Information: Quantifying the Degree of Covariation

    6 Protocol for Predicting Stabilizing Mutations

    7 Summary

    References

    Chapter Twelve. Enzyme Engineering by Targeted Libraries

    Abstract

    1 Introduction

    2 Screening Versus Selection

    3 The Merits of a Direct Screen: The Nerve Agent-Detoxifying Enzymes

    4 Hedging the Bets: Mutational Spiking Approaches

    5 Rational and Analytical Library Designs

    6 Summary

    References

    Chapter Thirteen. Generation of High-Performance Binding Proteins for Peptide Motifs by Affinity Clamping

    Abstract

    1 Introduction

    2 The Affinity Clamping Concept

    3 Design of Affinity Clamps

    4 Production and Characterization of Affinity Clamps

    5 Applications of Affinity Clamps

    6 Conclusion

    Acknowledgments

    References

    Chapter Fourteen. Engineering Fibronectin-Based Binding Proteins by Yeast Surface Display

    Abstract

    1 Introduction

    2 Engineering and Screening Approach of Fn3s

    3 Analysis of Individual Clones

    4 Summary

    Acknowledgments

    References

    Chapter Fifteen. Engineering and Analysis of Peptide-Recognition Domain Specificities by Phage Display and Deep Sequencing

    Abstract

    1 Introduction

    2 Directed Evolution of PDZ Variants

    3 Peptide Profiling of PDZ Variants

    4 Summary

    Acknowledgment

    References

    Chapter Sixteen. Efficient Sampling of SCHEMA Chimera Families to Identify Useful Sequence Elements

    Abstract

    1 Introduction

    2 SCHEMA Chimera Family Design Overview

    3 Prediction of Thermostable Chimeras by Linear Regression Modeling

    4 Summary

    Acknowledgments

    References

    Chapter Seventeen. Protein Switch Engineering by Domain Insertion

    Abstract

    1 Introduction

    2 Creation of Random Double-Stranded Breaks in Plasmids Containing the Acceptor DNA

    3 Repair, Purification and Dephosphorylation of Acceptor DNA

    4 Preparation of Insert DNA

    5 Ligation, Transformation, Recovery, and Storage of the Library

    6 Characterization of the Library

    Acknowledgments

    References

    Chapter Eighteen. Design of Chimeric Proteins by Combination of Subdomain-Sized Fragments

    Abstract

    1 Introduction

    2 Selecting the Starting Structures for Chimera Design

    3 Evaluation and Optimization of the Chimera

    4 Summary and Final Considerations

    References

    Chapter Nineteen. α-Helix Mimicry with α/β-Peptides

    Abstract

    1 Introduction

    2 Helical Secondary Structures from β-Peptides and α/β-Peptides

    3 Biological Function from Helical β-Peptides

    4 α-Helix Mimicry with α/β-Peptides

    5 Toward a General Approach for α-Helix Mimicry with Protease-Resistant α/β-Peptides

    Acknowledgments

    References

    Author Index

    Subject Index

Product details

  • No. of pages: 520
  • Language: English
  • Copyright: © Academic Press 2013
  • Published: February 14, 2013
  • Imprint: Academic Press
  • eBook ISBN: 9780123946294
  • Hardcover ISBN: 9780123942920

About the Serial Volume Editor

Amy Keating