Often considered the workhorse of the cellular machinery, proteins are responsible for functions ranging from molecular motors to signaling. The broad recognition of their involvement in all cellular processes has led to focused efforts to predict their functions from sequences, and if available, from their structures. An overview of current research directions, Computational Protein-Protein Interactions examines topics in the prediction of protein-protein interactions, including interference with protein-protein interactions and their design. Explores Computational Approaches to Understanding Protein-Protein Interactions Outlining fundamental and applied aspects of the usefulness of computations when approaching protein-protein interactions, this book incorporates different views of the same biochemical problem from sequence to structure to energetics. It covers protein-protein interaction prediction and dynamics, design, drug design for inhibition, and uses for the prediction of function. The text provides general chapters that overview the topic and also includes advanced material. The chapters detail the complexity of protein interaction studies and discuss potential caveats. Addresses the Next Big Problem in Molecular Biology While it is important to predict protein associations, this is a daunting task. Edited by two experts in the field and containing contributions from those at the forefront of research, the book provides a basic outline of major directions in computational protein-protein interactions research at the heart of functional genomics and crucial for drug discovery. It addresses the next big problem in molecular biology: how to create links between all the pieces of the cell jigsaw puzzle.

Since the conceptualization of the electromagnetic spectrum and development of the magnetron, microwave energy has been utilized in many aspects and disciplines of science. Although adopted by multiple industries over the past quarter of a century, it is only within the past few years that microwave irradiation has been evaluated as a useful tool for the biochemical and chemical preparation of proteins and other bio-molecules for proteomics and in particular mass spectrometric analysis. This book is an introduction to microwave-assisted bio-analytical methods with an emphasis on sample preparation for proteomic analyses. Its objective is to provide a history and background for the methods described and the book summarizes the development and application of these protocols from both the literature in this field as well as from the experiences of a variety of laboratories conducting microwave-assisted protocols. It describes the evolution and integration of microwave energy into the biosciences with particular emphasis on the proteomic arena and an in depth evaluation of a variety of techniques within the field of proteomics which benefit from microwave-irradiation is given. In addition to describing the evolution of the microwave-assisted methodologies, the book also offers a concise protocol section with practical advice on how to implement these methods in any laboratory. Mechanisms of action as well as an overview of the types of instrumentation available are described to help the reader develop the best experimental design for their own budget and experimental aims. Microwave-assisted proteomics is a rapidly evolving field and this book captures the main areas that fall under this emerging arena.

This unique text introduces students and researchers to the world of misfolded proteins, toxic oligomers, and amyloid assemblages, and the diseases of the brain that result. During the past few years the connections between failures in protein quality control and neurological disorders have been reinforced and strengthened by discoveries on multiple fronts. These findings provide novel insights on how amyloidogenic oligomers and fibrils form, interconvert from one state to another, and propagate from cell to cell and region to region. Starting with protein folding and protein quality control basics, the reader will learn how misfolded proteins can cause diseases ranging from prion diseases to Alzheimer's disease and Parkinson's disease to Huntington's disease, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Authoritative but written in a clear and engaging style, Fundamentals of Neurodegeneration and Protein Misfolding Disorders addresses one of today's forefront areas of science and medicine. The text emphasizes the new groundbreaking biophysical and biochemical methods that enable molecular-level explorations and the conceptual breakthroughs that result. It contains separate chapters on each of the major disease classes. Special emphasis is placed on those factors and themes that are common to the diseases, especially failures in synaptic transmission, mitochondrial control, and axonal transport; breakdowns in RNA processing; the potential role of environmental factors; and the confounding effects of neuroinflammation. The book is ideal for use in teaching at the advanced undergraduate and graduate levels, and serves as a comprehensive reference for a broad audience of students and researchers in neuroscience, molecular biology, biological physics and biomedical engineering.

Glutamine: Biochemistry, Physiology, and Clinical Applications describes the different functions of glutamine (Gln) in animals and humans. Gln is both a nutrient and a signaling molecule, and its functions go beyond those of a simple metabolic fuel or protein precursor. This book has gathered together, in an unbiased and critical manner, all the available evidence and research on Gln including pathology (neurological diseases, intestinal diseases, critical illness, and cancer), physiology (successful aging), catabolic states, immunity, and exercise. Special attention is given to the potential benefit of Gln in states of insulin resistance and the role of Gln as a "conditionally essential" amino acid. The contributors are either pioneers or experts in the area of Gln from all around the globe, including Australia, Brazil, Canada, Europe, China, and the United States. This book is a valuable source of information for nutrition scientists, medical doctors, sports scientists, food scientists, dietitians, and anyone interested in nutrition. It is also a valuable resource for students in these fields and will be an important addition to university libraries.

Protein folding and aggregation is the process by which newly synthesized proteins fold into the specific three-dimensional structures defining their biologically active states. It has always been a major focus of research in biochemistry and has often been seen as the unsolved second part of the genetic code. In the last 10 years we have witnessed a quantum leap in the research in this exciting area. Computational methods have improved to the extent of making possible to simulate the complete folding process of small proteins and the early stages of protein aggregation. Experimental methods have evolved to permit resolving fast processes of folding reactions and visualizing single molecules during folding. The findings from these novel experiments and detailed computer simulations have confirmed the main predictions of analytical theory of protein folding. In summary, protein folding research has finally acquired the status of a truly quantitative science, paving the way for more exciting developments in the near future. This unique book covers all the modern approaches and the many advances experienced in the field during the last 10 years. There is also much emphasis on computational methods and studies of protein aggregation which have really flourished in the last decade. It includes chapters in the areas that have witnessed major developments and are written by top experts including:computer simulations of folding, fast folding, single molecule spectroscopy, protein design, aggregation studies (both computational and experimental). Readers will obtain a unique perspective of the problems faced in the biophysical study of protein conformational behaviour in aqueous solution and how these problems are being solved with a multidisciplinary approach that combines theory, experiment and computer simulations. Protein Folding, Misfolding and Aggregation Classical Themes and Novel Approaches is essential reading for graduate students actively involved in protein folding research, other scientists interested in the recent progress of the field and instructors revamping the protein folding section of their biochemistry and biophysics courses.

Protein misfolding is a key feature of many disorders in humans, given that over twenty proteins are known to misfold and cause disease. In "Protein Folding, Misfolding, and Disease: Methods and Protocols," experts in the field present a collection of current methods for studying the analysis of protein folding and misfolding, featuring strategies for expressing and refolding recombinant proteins which can then be utilized in subsequent experiments. This detailed volume also covers methods for analyzing the formation of amyloid, protocols for determining the size and structure of native and misfolded proteins, as well as specific examples of where misfolded proteins can be examined using state-of -the-art technologies. Written in the highly successful "Methods in Molecular Biology " series format, chapters contain 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.

Up to date and authoritative, "Protein Folding, Misfolding, and Disease: Methods and Protocols" offers researchers the tools necessary to move ahead in this vital field."

The Protein Reviews series serves as a publication vehicle for reviews that focus on crucial contemporary and vital aspects of protein structure, function, evolution and genetics. Volumes are published online first, prior to publication in a printed book. Chapters are selected according to their importance to the understanding of biological systems, relevance to the unravelling of issues associated with health and disease, or impact on scientific or technological advances and developments. Volume 22 presents six review chapters authored by experts in related fields. The first chapter covers carotenoid-protein interactions. Chapter two addresses the non-continuum of eukaryotic transcriptional regulation. The third chapter reviews the structure of the regulatory and catalytic domains of the photoreceptor phosphodiesterase (PDE6) holoenzyme. Chapter four reviews the current knowledge on small molecule compounds that have been evaluated as rhodopsin modulators to be considered as leads for the development of novel therapies for retinitis pigmentosa. Chapter five deals with Plasticity-associated functionality and inhibition of the HIV protease. Finally, chapter six covers single-run catalysis and kinetic control of human telomerase holoenzyme. This volume is intended for research scientists, clinicians, physicians and graduate students in the fields of biochemistry, cell biology, molecular biology, immunology and genetics.

This book presents pioneering findings on the characterization of cellular regulation and function for three recently identified protein posttranslational modifications (PTMs): lysine malonylation (Kmal), glutarylation (Kglu) and crotonylation (Kcr). It addresses three main topics: (i) Detecting Kmal substrates using a chemical reporter, which provides important information regarding the complex cellular networks modulated by Kmal; (ii) Identifying Kglu as a new histone PTM and assessing the direct impact of histone Kglu on chromatin structure and dynamics; and (iii) Revealing Sirt3's value as a regulating enzyme for histone Kcr dynamics and gene transcription, which opens new avenues for examining the physiological significance of histone Kcr. Taken together, these studies provide information critical to understanding how these protein PTMs are associated with various human diseases, and to identifying therapeutic targets for the dysregulation of these novel protein markers in various human diseases.

Leading researchers are specially invited to provide a complete understanding of a key topic within the multidisciplinary fields of physiology, biochemistry and pharmacology. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

This book explores the broad and diverse biological and physiological impacts of established and newly discovered cyclic di-nucleotide second messenger signaling systems, while also providing descriptions of the intriguing biochemical characteristics of multiple turnover enzymes and receptors. The respective chapters discuss the commonalities and diversity of cyclic di-GMP, cyclic di-AMP and recently discovered cyclic GMP-AMP signaling systems in manifold Gram-negative and Gram-positive bacteria. The global human pathogens Mycobacterium tuberculosis, Vibrio cholerae, Salmonella typhimurium, Escherichia coli and Streptococcus pneumoniae, the facultative human pathogen Pseudomonas aeruginosa, global plant pathogens as exemplified by Xanthomonas campestris and Burkholderia spp., and the omnipresent probiotic Lactobacilli, as well as environmentally important photoautotrophic cyanobacteria, the multicellular Myxococcus xanthus, and chemolithotrophic Acidithiobacillus are among the representatives of the microbial kingdom that are described. In turn, the various aspects of bacterial physiology affected by these signaling systems- e.g. biofilm formation and dispersal, the cell cycle, motility, virulence, production of antimicrobials, fundamental metabolism and osmohomeostasis - are discussed in detail in the context of different microorganisms. Dedicated chapters focus on the population diversity of cyclic dinucleotide signaling systems, their tendency to be horizontally transferred, the cyclic di-GMP signaling system in the social amoeba Dictyostelium, honorary cyclic (di)nucleotides, and the development of strategies for interfering with cyclic dinucleotide signaling in order to manipulate microbial behavior. Taken together, the chapters provide an authoritative source of information for a broad readership: beginners and advanced researchers from various disciplines; individuals seeking a broad overview of cyclic di-nucleotide signaling; and those who want to learn more about specific aspects. Also featuring reviews with a forward-looking perspective, the book offers a valuable source of inspiration for future research directions.

Utilizing high speed computational methods to extrapolate to the rest of the protein universe, the knowledge accumulated on a subset of examples, protein bioinformatics seeks to accomplish what was impossible before its invention, namely the assignment of functions or functional hypotheses for all known proteins. The Ten Most Wanted Solutions in Protein Bioinformatics considers the ten most significant problems occupying those looking to identify the biological properties and functional roles of proteins. -Problem One considers the challenge involved with detecting the existence of an evolutionary relationship between proteins. -Two and Three studies the detection of local similarities between protein sequences and analysis in order to determine functional assignment. -Four, Five, and Six look at how the knowledge of the three-dimensional structures of proteins can be experimentally determined or inferred, and then exploited to understand the role of a protein. -Seven and Eight explore how proteins interact with each other and with ligands, both physically and logically. -Nine moves us out of the realm of observation to discuss the possibility of designing completely new proteins tailored to specific tasks. -And lastly, Problem Ten considers ways to modify the functional properties of proteins. After summarizing each problem, the author looks at and evaluates the current approaches being utilized, before going on to consider some potential approaches. introbul Features

Using a geometric perspective, Protein Geometry, Classification, Topology, and Symmetry reviews and analyzes the structural principals of proteins with the goal of revealing the underlying regularities in their construction. It also reviews computer methods for structure analysis and the automatic comparison and classification of these structures with an analysis of the statistical significance of comparing different shapes. Following an analysis of the current state of protein classification, the authors explore more abstract geometric and topological representations, including the occurrence of knotted topologies. The book concludes with a consideration of the origin of higher-level symmetries in protein structure. The authors focus on simple geometric methods that are deterministic rather than probabilistic and on the more abstract simplifications of protein structure that allow a better understanding of the overall fold of the structure. Most of the methods described in this book have corresponding computer programs. These can be found (as C source code) at the ftp site of the Division of Mathematical Biology at the National Institute for Medical Research. This collection of ideas contains pedagogical material that make it ideal for post-graduate courses as well as new ideas and results essential for researchers investigating protein structures.

This book brings together recent, international contributions to the study of gluten proteins from leading experts in the field. Gluten proteins have gained greater importance due not only to their fundamental role in determining technological quality of wheat end products, but also to the apparently increased number of people showing different degrees of gluten intolerance or allergy. Along with classical subjects such as gluten genetics, quality and rheology, The Gluten Proteins covers new tools and research fields, including the use of proteomics and genomics. Furthermore, information dedicated to intolerances and allergies is included and opens the possibility to widen future research opportunities, promoting cooperation between wheat breeders, medical researchers and gluten chemists and geneticists. The Gluten Proteins provides an authoritative source of information for researchers, professionals and postgraduate students wishing to increase their knowledge of the molecular bases of gluten functionality and nutritional role, as well as touching on possible future research opportunities.

This book is unique; the factual content and ideas it expounds are only just beginning to be touched upon in standard texts. Protein Electron Transfer is a major collaborative effort by leading experts and explores the molecular basis of the rapidly expan

Omics is an emerging and exciting area in the field of science and medicine. Numerous promising developments have been elucidated using omics (including genomics, transcriptomics, epigenomics, proteomics, metabolomics, interactomics, cytomics and bioinformatics) in cancer research. The development of high-throughput technologies that permit the solution of deciphering cancer from higher dimensionality will provide a knowledge base which changes the face of cancer understanding and therapeutics.

This is the first book to provide such a comprehensive coverage of a rapidly evolving area written by leading experts in the field of omics. It complies and details cutting-edge cancer research that covers the broad advances in the field and its application from cancer-associated gene discovery to drug target validation. It also highlights the potential of using integration approach for cancer research.

This unique and timely book provides a thorough overview of developing omics, which will appeal to anyone involved in cancer research. It will be a useful reference book for graduate students of different subjects (medicine, biology, engineering, etc) and senior scientists interested in the fascinating area of advanced technologies in cancer research.

Readership: This is a precious book for all types of readers cancer researchers, oncologists, pathologists, biologists, clinical chemists, pharmacologists, pharmaceutical specialists, biostatisticians, and bioinformaticists who want to expand their knowledge in cancer research."

This volume explores current technologies used to investigate the formation, insertion, and function of metalloclusters associated with proteins. Chapters describe relevant topics about Fe-S cluster metabolism are explored through genetic, biochemical, spectroscopic methods. 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 tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Fe-S Proteins: Methods and Protocols aims to be a useful practical guide to researchers to help further their study in this field.

The aim of the Protein Reviews is to serve as a publication vehicle for review articles that focus on crucial current vigorous aspects of protein structure, function, evolution and genetics. The volumes will appear online before they are published in a printed book. Articles are selected according to their importance to the understanding of biological systems, their relevance to the unravelling of issues associated with health and disease or their impact on scientific or technological advances and developments. Volume 19 focusses on Purinergic receptors, also termed purinoceptors. These are plasma membrane proteins present in nearly all mammalian tissues. They participate in a number of cell functions that include proliferation and migration of neural stem cells, vascular reactivity, apoptosis and cytokine secretion and have been associated with learning and memory, feeding conduct, movement and sleep. They facilitate relaxation of smooth muscle of the gut in response to adenosine (P1 receptors) or ATP (P2 receptors). The chapters in this volume are authored by experts in the field. They deal with aspects of structure and biological activity of selected receptor proteins. The first chapter in this volume reviews the current research on the Mechanism of channel gating and regulation of the activity of calcium-activated chloride channel ANO1. This is followed by a chapter dealing with Structure and function of the two-component cytotoxins of Staphylococcus aureus and a chapter on Membrane Fusion and Infection involving the Influenza virus Hemagglutinin. The fourth chapter reviews the impact of arrhythmogenic mutations through the structural determination of the L-type voltage-gated calcium channel. Then there is a chapter that discusses some open questions pertaining to histone post-translational modifications and nucleosome organization in transcriptional regulation. The next chapter deals with regulation of the extracellular SERPINA5 (protein C inhibitor) penetration through cellular membranes. This is followed by a chapter on coding of Class I and II aminoacyl-tRNA synthetases; a chapter on regulation of nephrin phosphorylation in diabetes and chronic kidney injury and a chapter on The Structure-Forming Juncture in oxidative protein folding and the events in the ER. Finally the last chapter deals with the polyspecificity of anti-lipid antibodies and its relevance to the development of autoimmunity. This volume is intended for research scientists, clinicians, physicians and graduate students in the fields of biochemistry, cell biology, molecular biology, immunology and genetics.

Based upon a workshop entitled "The Small HSP World" held in Quebec 2-5 October 2014. Twenty-five scientists provided chapters for the book. The chapters are from the best scientists currently working in this field. These colleagues include Arrigo, Benesch, Benjamin, Buchner-Haslbeck-Weinkauf, Benndorf, Boelens, Carra, Chang, Currie, Ecroyd, Emanuelsson, Fu, Garrido, Golenhofen, Gusev, Hightower, Kampinga, Lavoie, MacRae, Quinlan, Tanguay, Vierling, Vigh, Weeks and Wu. Briefly, the book starts with the structure of small heat shock proteins, moving to their functions and finishing with their involvement in diseases. Although this is quite broad, the structural aspect will be the unifying theme of the book.

Focusing on model systems for the study of structure, folding, and association in the membrane, Membrane Proteins: Folding, Association, and Design presents an overview of methods that can be applied to these intricate systems. The volume is divided into four detailed sections, covering association of transmembrane helices, interactions with the lipid bilayer, NMR methods, as well as a variety of engineering approaches. 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. Authoritative and practical, Membrane Proteins: Folding, Association, and Design serves as an ideal guide for researchers reaching for the tantalizing possibility of designing novel membrane proteins with tailored functionality.

A comprehensive introduction to the art and science used by the biochemist and process engineer in the design and optimization of large-scale protein-purification processes. Covers the basics of proteins' properties, the unit operations involved in protein purification as well as important related issues of process design, integration with upstream operations, cost and timing to market. Includes an abundance of figures and tables.

This detailed collection gathers both established and recent technical procedures to study the Endosomal Sorting Complex Required for Transport (ESCRT) complexes in a wide range of biological systems: Archaea, A. thaliana, U. maydis, S. cerevisiae, S. pombe, C. elegans, D. melanogaster, and mammalian cells. Opening with a section on imaging techniques, the book continues with chapters covering biochemical approaches presenting strategies for production and characterization of recombinant ESCRT proteins, or of specific ESCRT protein domains, as well as genetic and proteomic experimental approaches. Written for the highly successful Methods in Molecular Biology series, chapters include introduction 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. Authoritative and practical, The ESCRT Complexes: Methods and Protocols serves as a compact guide for researchers interested in establishing an integrated approach to investigate the ESCRT machinery functions in cell biology.

This detailed collection explores techniques involved in the main strategies of nanopore sensing, such as translocation, analyte trapping, and interactions with external binding sites. Opening with a section on nanopore design and nanopore production, the book continues with parts devoted to various biological nanopores, nanopore engineering, and their uses in single molecule sensing, computational methods to study intrinsic nanopore behavior, characterizing the specific translocation activity of a vesicle particle through a nanopore, as well as the use of the technique droplet interface bilayer (DIB) in nanopore and membrane biophysical studies. 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. Authoritative and practical, Nanopore Technology: Methods and Protocols, with its focus on nanopore technology and biomolecule characterization, will hold the interest of the biophysicists, biochemists, bioengineers, and molecular biologists who are working toward further understanding this key field of research.

The broad range of G protein-coupled receptors (GPCRs) encompasses all areas of modern medicine and have an enormous impact on the process of drug development. Using disease-oriented methods to cover everything from screening to expression and crystallization, G Protein-Coupled Receptors in Drug Discovery describes the physiological roles of GPCRs and their involvement in various human diseases. The book presents current approaches in drug discovery that include target selection, establishment of screening and functional assays. It also covers recombinant GPCR expression for drug screening and structural biology, different methods for structural characterization of GPCRs, and the importance of bioinformatics. The book has been carefully edited to avoid overlapping information, some duplication has been intentionally permitted so that each chapter can function as an independent unit. Providing in-depth discussions on structure and dynamics of GPCRs, this book outlines the importance of the GPCRs to drug discovery in general and drug targets specifically. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.

Following the announcement of the draft sequence of the human genome and the completion of many others, attention is now increasingly turning to the analysis of the proteins encoded by genomes - proteomics. This is a rapidly emerging research area and this book reviews recent developments in proteomics and compares them with current genomics technologies. The book is written by experts, from academia and industry, who review their area in a concise yet easy to understand style, providing a comprehensive review volume that integrates genomics with proteomics. This is the first book to address the subject at an undergraduate level.

Protein engineering has proved to be one of the more fruitful technological approaches in biotechnology, being both very powerful and able to generate valuable intellectual property. This book aims to present examples in which the application of protein engineering has successfully solved problems arising in industrial biotechnology. There is a section on its use to enhance purification of recombinant proteins. The use of protein engineering to modify the activity or the stability of industrial enzymes from lipases to proteases, from carboxypeptidases to glucanases and glucosidases, and from pectin modifying enzymes to enzymes able to degrade recalcitrant compounds is extensively covered. It is shown how areas as diverse as agrofood technology, fine chemistry, detergents, bioremediation and biosensors receive significant contributions from protein and solvent engineering.
The application of protein engineering to health care is also covered, from the development of new vaccines to new potential therapeutic proteins. A specific notation is given to protein engineering in the development of target molecules for drug discovery.
International in scope, the many contributions are drawn from academia and industry. The text should be of interest to students and researchers in industrial biotechnology as well as to everybody interested in basic research in protein structure, molecular genetics, bio-organic chemistry, biochemistry, agrobiotechnology, pharmaceutical sciences and medicine.