Protein Design / Edition 1

by Raphael Guerois, Manuela López de la Paz

Overview

Proteins have evolved through selective pressure to accomplish specific functions. The functional properties of proteins depend upon their thr- dimensional structures, which result from particular amino acid sequences folding into tightly packed domains. Thus, to understand and modulate protein function rationally, one definitely needs methods and algorithms to predict and decipher how amino acid sequences shape three-dimensional structures. Protein design aims precisely at providing the tools to achieve this goal. The predictive power of rational protein design methods has dramatically increased over the past five years. A broad range of studies now illustrate how the sequence of proteins and peptides can be tuned to engineer biological tools with intended properties (1–3). The extensive characterization of peptides and protein mutants has enormously benefited the understanding of protein sequence-to-structure relationships. Synergies between computational and experimental approaches have also added momentum to the advancing limits of design methods. The potential applications in fundamental biochemistry and in biotechnology justify the considerable excitement that this progress has generated within the research community. The field is probably mature enough so that expert knowledge can assist researchers of diverse disciplines to rationally create or modify their favorite protein. Thus, the aim of Protein Design: Methods and Prools is to account for the most up-to-date protein design and engineering strategies so that readers can undertake their own projects with maximum confidence in a successful return. The basic concepts underlying rational design of proteins are intimately related to their three-dimensional structures.

Product Details

ISBN-13:	9781617376597
Publisher:	Springer-Verlag New York, LLC
Publication date:	11/19/2010
Series:	Methods in Molecular Biology , #340
Edition description:	Softcover reprint of hardcover 1st ed. 2006
Pages:	300
Product dimensions:	5.98(w) x 9.02(h) x 0.03(d)

Table of Contents

Design of Structural Elementary Motifs.- Structure and Stability of the—-Helix.- De novo Design of Monomeric—-Hairpin and—-Sheet Peptides.- De novo Proteins From Binary-Patterned Combinatorial Libraries.- Non-Protein Amino Acids in the Design of Secondary Structure Scaffolds.- Design and Synthesis of—-Peptides With Biological Activity.- Design Of Entire Proteins And Protein Complexes.- Design of Miniproteins by the Transfer of Active Sites Onto Small-Size Scaffolds.- Consensus Design as a Tool for Engineering Repeat Proteins.- Multiple Sequence Alignment as a Guideline for Protein Engineering Strategies.- Sequence Search Methods and Scoring Functions for the Design of Protein Structures.- Prediction of Protein–Protein Interaction Based on Structure.- Electrostatic Design of Protein–Protein Association Rates.- Design of Amyloidogenic Polypeptides and Amyloid Inhibitors.- Peptide Model Systems for Amyloid Fiber Formation Design Strategies and Validation Methods.- Protein Misfolding Disorders and Rational Design of Antimisfolding Agents.

Editorial Reviews

"...provides a comprehensive guide to the methods used at every stage of the protein-design process..." - ChemBioChem

"...combines a thorough theoretical foundation with detailed prools and will be invaluable to all researchers in the area, from graduate students to senior investigators." -ChemBioChem

From the Publisher

Reviewer: Eugene A Davidson, PhD (Georgetown University School of Medicine)
Description: This book surveys several methods currently used to predict protein structure and the application of these tools to design.
Purpose: The goal is to present methods for protein design that can be adapted for diverse problems — a worthy objective but not reachable in a practical sense. What is presented is suitable and correct, but falls far short of the ambitious title.
Audience: Scientists interested in the latest thinking about protein design/structure will find material of value here. As with so many books, a critical analysis of shortcomings and major challenges is lacking. The editors have assembled a capable group of contributors, but prominent thought leaders are absent.
Features: One Holy Grail of biological science is the ability to predict protein structure and behavior from knowledge of the primary sequence, a target fashioned from the classical experiment of Anfinsen. Although that problem has yet to be solved at a level of resolution that most would desire, thinking has moved beyond to the more complex issue of designing a protein to fit a given requirement set. This book attempts to provide an up-to-date survey of methods employed in this arena, with a naturally heavy emphasis on computer-driven approaches. The book is divided into three sections: the initial material deals with simple secondary structural features such as the alpha-helix; the next section with whole protein design and methods for predicting protein-protein interactions; the short final chapters focus on prions and similar proteins. The attempt is laudable and the chapters well prepared. Much of the material will be of interest to scientists in the area and of value to those outside. However, we are a long way from protein design. It seems unlikely that we will soon be able to produce to order a molecule with specific catalytic properties and designed regulatory interactions (be they covalent modifications or allosteric effectors). Likewise for approaches that rely on sequence gazing, no matter how sophisticated the algorithm. Comparison of trypsin (a serine protease, mainly beta-sheet) with subtilisin (a serine protease, mainly helical) could not reveal that both use the same catalytic triad. It is also unlikely that subtle conformational changes, essential to real-life enzyme function can be designed, even in rough form. Thus, we are just a few seconds after the big bang in this domain. Nevertheless, it is of value to understand current thinking, although the book would have been improved by a section focused on limitations and major hurdles.
Assessment: The title is overly ambitious; lack of a critical assessment detracts and several major figures in the field have not contributed.

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