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Researchers in structural genomics continue to search for biochemical and cellular functions of proteins as well as the ways in which proteins assemble into functional pathways and networks using either experimental or computational approaches. Based on the experience of leading international experts, Structural Genomics and High Throughput Stru
Structural Genomics and Drug Discovery: Methods and Protocols focuses on high throughput structure determination methods and how they can be applied to lay the groundwork for structure aided drug discovery. The methods and protocols that are described can be applied in any laboratory interested in using detailed structural information to advance the initial stages of drug discovery. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Structural Genomics and Drug Discovery: Methods and Protocols seeks to aid scientists in the further study into structural genomics approach as an efficient initial step toward drug discovery and the methods described will be useful to anyone interested in moving in this direction.
Structural genomics is the systematic determination of 3-dimensional structures of proteins representative of the range of protein structure and function found in nature. The goal is to build a body of structural information that will predict the structure and potential function for almost any protein from knowledge of its coding sequence. This is essential information for understanding the functioning of the human proteome, the ensemble of tens of thousands of proteins specified by the human genome. While most structural biologists pursue structures of individual proteins or protein groups, specialists in structural genomics pursue structures of proteins on a genome wide scale. This implies large-scale cloning, expression and purification. One main advantage of this approach is economy of scale. Examines the three dimensional structure of all proteins of a given organism, by experimental methods such as X-ray crystallography and NMR spectroscopy Looks at structural genomics as a foundation of drug discovery as discovering new medicines is becoming more challenging and the pharmaceutical industry is looking to new technologies to help in this mission
Structural genomics is the systematic determination of 3-D structures of proteins representative of the range of protein structure and function found in nature. The goal is to build a body of structural information that will predict the structure and potential function for almost any protein from knowledge of its coding sequence. This is essential information for understanding the functioning of the human proteome, the ensemble of tens of thousands of proteins specified by the human genome. While most structural biologists pursue structures of individual proteins or protein groups, specialists in structural genomics pursue structures of proteins on a genome wide scale. This implies large-scale cloning, expression and purification. One main advantage of this approach is economy of scale. Key Features *Examines the three dimensional structure of all proteins of a given organism, by experimental methods such as X-ray crystallography and NMR spectroscopy * Looks at structural genomics as a foundation of drug discovery as discovering new medicines is becoming more challenging and the pharmaceutical industry is looking to new technologies to help in this mission.
Structural genomics is the systematic determination of 3-D structures of proteins representative of the range of protein structure and function found in nature. The goal is to build a body of structural information that will predict the structure and potential function for almost any protein from knowledge of its coding sequence. This is essential information for understanding the functioning of the human proteome, the ensemble of tens of thousands of proteins specified by the human genome. While most structural biologists pursue structures of individual proteins or protein groups, specialists in structural genomics pursue structures of proteins on a genome wide scale. This implies large-scale cloning, expression and purification. One main advantage of this approach is economy of scale. Examines the three dimensional structure of all proteins of a given organism, by experimental methods such as X-ray crystallography and NMR spectroscopy Looks at structural genomics as a foundation of drug discovery as discovering new medicines is becoming more challenging and the pharmaceutical industry is looking to new technologies to help in this mission
Structural biology is becoming a routine technique for structure de termination in pharmaceutical industries. The advances in molecular biology, crystal handling and data collection techniques, tunable syn chrotron radiation sources, and high-performance computing have all contributed to developments such as the production and expression of tailored protein domains, the use of the MAD (Multiple Anomalous Dispersion) method, and the collection of X-ray data from tiny crystals at cryogenic temperature. The number of protein structures deposited in the Protein Databank has increased tremendously over the last 3-4 years. Since 1997, more than 1,500 structures have been deposited each year, and during the first 7 months of this year, 1,500 protein structures were already deposited. The numerous initiatives in the field of "structural genomics" distributed all over the world have led to the development of techniques for high-throughput structure determina tion, thereby contributing to the increase in the determination of three dimensional protein structures. This structural information is being ex plored in various ways in the drug discovery process. It is not only used in structure-based drug design of new low-molecular-weight li gands, but also in the early stages of target validation and assessment. With the number of protein sequences without significant homology to well-known proteins increasing, the technique of structure-sequence compatibility (threading) is increasingly used to assign a function to a given protein fold.
The objective of this volume is to provide readers with a current view of all aspects of the 'pipeline' that takes protein targets to structures and how these have been optimised. This volume includes chapters describing, in-depth, the individual steps in the Structural Genomics pipeline, as well as less detailed overviews of individual Structural Genomics initiatives. It is the first book of protocols to cover techniques in a new and emerging field.
The role played by structural proteomics in the first decade of the 21st century is equivalent to that played by the Human Genome Project in the last decade of the 20th century. The development of high-throughput technologies that permit the solution of hundreds of 3D structures of individual proteins, protein-protein complexes and protein-drug complexes, just by one laboratory in a single year, will provide a knowledge base which will change the face of structural biology. This will have an immediate influence on medicinal chemistry and molecular pharmacology, as well as an increasing impact on such disciplines as neurobiology, developmental biology, immunology and molecular medicine.This book presents a state-of-the-art overview of the structural proteomics field, ranging from policy issues related to funding and goals, through the high-throughput procedures for protein production, to the solution of the structures of proteins and higher-order entities, via a multidisciplinary approach involving molecular biology, X-ray crystallography, NMR and electron microscopy, as well as bioinformatics analysis. This is the first book to provide such a comprehensive coverage of a rapidly evolving field.
Structural genomics is the systematic determination of 3-D structures of proteins representative of the range of protein structure and function found in nature. The goal is to build a body of structural information that will predict the structure and potential function for almost any protein from knowledge of its coding sequence. This is essential information for understanding the functioning of the human proteome, the ensemble of tens of thousands of proteins specified by the human genome. While most structural biologists pursue structures of individual proteins or protein groups, specialists in structural genomics pursue structures of proteins on a genome wide scale. This implies large-scale cloning, expression and purification. One main advantage of this approach is economy of scale. Examines the three dimensional structure of all proteins of a given organism, by experimental methods such as X-ray crystallography and NMR spectroscopy Looks at structural genomics as a foundation of drug discovery as discovering new medicines is becoming more challenging and the pharmaceutical industry is looking to new technologies to help in this mission
This updated edition emphasizes the benefits of structural genomics to the wider structural research community with a diverse range of applicable methods. The book opens with an extensive section on protein production, including new methodologies for membrane and metal-binding proteins, as well as high-throughput protein production and screening. It continues with sections on structural analyses and data management, as well as modeling, simulation, and visualization. Overall, the spectrum of topics reflects the trend towards tackling more diverse challenges of studying macromolecular machineries and complexes. Written for the highly successful Methods in Molecular Biology series, chapters include the type of detail and key implementation advice to ensure successful results. Authoritative and up-to-date, Structural Genomics: General Applications, Second Edition serves as a vital guide to structural biologists in small to medium-sized laboratories seeking to better utilize this powerful area of study. Chapter 11 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com. For further details see license information in the chapter.