Description
Proteins possess a broad range of structural and functional properties that are unmatched by any other class of biological molecules. Amazingly, nature has arranged simple atoms and chemical bonds in such a way to facilitate complex biological processes like molecular recognition and catalysis. Nature has also inspired many scientists and engineers to design and create their own customized proteins. These engineered proteins can serve as novel molecular tools for scientific, medical, and industrial applications, thus addressing many needs unmet by naturally occurring proteins.
Protein engineering requires identification of particular amino acid sequences that will result in desired structural and functional properties. Despite recent advances in the field, however, protein engineering remains as much an art as it is a science. Engineering an arbitrary protein structure or function remains a formidable challenge, because the rules defining sequence-structure-function relationships are still not well understood. Even with refined quantitative models, the large degrees of freedom present in a typical protein do not easily allow identification of optimal sequences using currently available computational techniques. Furthermore, the complexity of proteins present engineering challenges whose solutions will most likely require a combination of experimental and computational approaches.
This book discusses two general strategies commonly used to engineer new proteins: diversity-oriented protein engineering and computational protein design. Diversity-oriented protein engineering, or directed evolution, identifies protein variants with desired properties from a large pool of mutants. As such, its success depends on generating sufficient sequence diversity and employing sensitive highthroughput assays. Computational protein design, on the other hand, generates and screens protein sequences in silico before synthesizing them in the laboratory. This is still an unfamiliar concept to many, so an important goal of this book is to demystify the subject by describing its development and current implementations. Structurebased protein engineering similarly uses computation to facilitate the discovery of interesting protein sequences. However, computational protein design places emphasis on both engineering new, useful proteins and on testing sequence-structure relationships. In this regard, it shares a deep philosophical root with protein folding, which similarly seeks to understand the relationship between protein sequence and tertiary structure.
Contents
- Preface
- Editors
- Contributor List
- Chapter 1 Phage Display Systems for Protein Engineering
Andreas Ernst and Sachdev S. Sidhu
- Chapter 2 Cell Surface Display Systems for Protein Engineering
Sarah J. Moore, Mark J. Olsen, Jennifer R. Cochran, and Frank V. Cochran
- Chapter 3 Cell-Free Display Systems for Protein Engineering
Pamela A. Barendt and Casim A. Sarkar
- Chapter 4 Library Construction for Protein Engineering
Daša Lipovšek, Marco Mena, Shaun M. Lippow, Subhayu Basu, and Brian M. Baynes
- Chapter 5 Design and Engineering of Synthetic Binding Proteins Using Nonantibody Scaffolds
- Chapter 6 Combinatorial Enzyme Engineering.
Patrick C. Cirino and Christopher S. Frei
- Chapter 7 Engineering of Therapeutic Proteins
Fei Wen, Sheryl B. Rubin-Pitel, and Huimin Zhao
- Chapter 8 Protein Engineered Biomaterials
Cheryl Wong Po Foo and Sarah C. Heilshorn
- Chapter 9 Protein Engineering Using Noncanonical Amino Acids
Deniz Yüksel , Diren Pamuk, Yulia Ivanova, and Krishna Kumar
- Chapter 10 Computer Graphics, Homology Modeling, and Bioinformatics
David F. Green
- Chapter 11 Knowledge-Based Protein Design
Michael A. Fisher, Shona C. Patel, Izhack Cherny, and Michael H. Hecht
- Chapter 12 Molecular Force Fields
Patrice Koehl
- Chapter 13 Rotamer Libraries for Molecular Modeling and Design of Proteins
Hidetoshi Kono
- Chapter 14 Search Algorithms
Julia M. Shifman and Menachem Fromer
- Chapter 15 Modulating Protein Structure
M.S. Hanes, T.M. Handel, and A.B. Chowdry
- Chapter 16 Modulation of Intrinsic Properties by Computational Design.
Vikas Nanda, Fei Xu, and Daniel Hsieh
- Chapter 17 Modulating Protein Interactions by Rational and Computational Design
Jonathan S. Marvin and Loren L. Looger
- Chapter 18 Future Challenges of Computational Protein Design.
Eun Jung Choi, Gurkan Guntas, and Brian Kuhlman