While the genomic revolution has quickly led to the deposit of more than 30,000 structures in the protein data bank (PDB), less than one percent of those contributions represent membrane proteins despite the fact that membrane proteins constitute some 20 percent of all proteins. This discrepancy becomes significantly troublesome when it is coupled
Proteins lie at the heart of almost all biological processes and have an incredibly wide range of activities. Central to the function of all proteins is their ability to adopt, stably or sometimes transiently, structures that allow for interaction with other molecules. An understanding of the structure of a protein can therefore lead us to a much improved picture of its molecular function. This realisation has been a prime motivation of recent Structural Genomics projects, involving large-scale experimental determination of protein structures, often those of proteins about which little is known of function. These initiatives have, in turn, stimulated the massive development of novel methods for prediction of protein function from structure. Since model structures may also take advantage of new function prediction algorithms, the first part of the book deals with the various ways in which protein structures may be predicted or inferred, including specific treatment of membrane and intrinsically disordered proteins. A detailed consideration of current structure-based function prediction methodologies forms the second part of this book, which concludes with two chapters, focusing specifically on case studies, designed to illustrate the real-world application of these methods. With bang up-to-date texts from world experts, and abundant links to publicly available resources, this book will be invaluable to anyone who studies proteins and the endlessly fascinating relationship between their structure and function.
Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics, Three Volume Set combines elements of computer science, information technology, mathematics, statistics and biotechnology, providing the methodology and in silico solutions to mine biological data and processes. The book covers Theory, Topics and Applications, with a special focus on Integrative –omics and Systems Biology. The theoretical, methodological underpinnings of BCB, including phylogeny are covered, as are more current areas of focus, such as translational bioinformatics, cheminformatics, and environmental informatics. Finally, Applications provide guidance for commonly asked questions. This major reference work spans basic and cutting-edge methodologies authored by leaders in the field, providing an invaluable resource for students, scientists, professionals in research institutes, and a broad swath of researchers in biotechnology and the biomedical and pharmaceutical industries. Brings together information from computer science, information technology, mathematics, statistics and biotechnology Written and reviewed by leading experts in the field, providing a unique and authoritative resource Focuses on the main theoretical and methodological concepts before expanding on specific topics and applications Includes interactive images, multimedia tools and crosslinking to further resources and databases
Fundamentals of Molecular Structural Biology reviews the mathematical and physical foundations of molecular structural biology. Based on these fundamental concepts, it then describes molecular structure and explains basic genetic mechanisms. Given the increasingly interdisciplinary nature of research, early career researchers and those shifting into an adjacent field often require a "fundamentals" book to get them up-to-speed on the foundations of a particular field. This book fills that niche.
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
With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins
This updated and expanded volume reflects the current state of the structural protein field with improved and refined protocols that have been applied to particularly challenging proteins, notably integral membrane proteins and multi-protein complexes. Structural Proteomics: High-Throughput Methods, Second Edition begins by exploring the resources available for curation, annotation, and structure prediction in silico, and continues with methods for sample preparation of both proteins and crystals, as well as structural characterization techniques. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and up-to-date, Structural Proteomics: High-Throughput Methods, Second Edition will aid researchers in expanding our knowledge of this vital and expansive area of protein science.
Proteins: Structure and Function is a comprehensive introduction to the study of proteins and their importance to modern biochemistry. Each chapter addresses the structure and function of proteins with a definitive theme designed to enhance student understanding. Opening with a brief historical overview of the subject the book moves on to discuss the ‘building blocks’ of proteins and their respective chemical and physical properties. Later chapters explore experimental and computational methods of comparing proteins, methods of protein purification and protein folding and stability. The latest developments in the field are included and key concepts introduced in a user-friendly way to ensure that students are able to grasp the essentials before moving on to more advanced study and analysis of proteins. An invaluable resource for students of Biochemistry, Molecular Biology, Medicine and Chemistry providing a modern approach to the subject of Proteins.
This book reviews current techniques used in membrane protein structural biology, with a strong focus on practical issues. The study of membrane protein structures not only provides a basic understanding of life at the molecular level but also helps in the rational and targeted design of new drugs with reduced side effects. Today, about 60% of the commercially available drugs target membrane proteins and it is estimated that nearly 30% of proteins encoded in the human genome are membrane proteins. In recent years much effort has been put towards innovative developments to overcome the numerous obstacles associated with the structure determination of membrane proteins. This book reviews a variety of recent techniques that are essential to any modern researcher in the field of membrane protein structural biology. The topics that are discussed are not commonly found in textbooks. The scope of this book includes: Expression screening using fluorescent proteins The use of detergents in membrane protein research The use of NMR Synchrotron developments in membrane protein structural biology Visualisation and X-ray data collection of microcrystals X-ray diffraction data analysis from multiple crystals Serial millisecond crystallography Serial femtosecond crystallography Membrane protein structures in drug discovery The information provided in this book should be of interest to anyone working in the area of structural biology. Students will find carefully prepared overviews of basic ideas and advanced protein scientists will find the level of detail required to apply the material directly to their day to day work. Chapters 4, 5, 6, 8 and 9 of this book are published open access under a CC BY 4.0 license at link.springer.com.
