This book discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). The properties of IDPs and IDPRs are highly complementary to those deriving from the presence of a unique and well-defined three-dimensional fold. Ignored for a long time in high-resolution studies of proteins, intrinsic protein disorder is now recognized as one of the key features for a large variety of cellular functions, where structural flexibility presents a functional advantage in terms of binding plasticity and promiscuity and this volume explores this exciting new research. Recent progress in the field has radically changed our perspective to study IDPs through NMR: increasingly complex IDPs can now be characterized, a wide range of observables can be determined reporting on the structural and dynamic properties, computational methods to describe the structure and dynamics are in continuous development and IDPs can be studied in environments as complex as whole cells. This volume communicates the new exciting possibilities offered by NMR and presents open questions to foster further developments. Intrinsically Disordered Proteins Studied by NMR Spectroscopy provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

Focuses on Biology, Pharmacology, and Therapeutic Applications The study and diverse applications of bioactive peptides traverse many sub-disciplines within chemistry, biology, physics, and medicine. Answering a long-standing need, Bioactive Peptides focuses on the biology, pharmacology, and therapeutic applications of endogenous peptide mediators and their analogues. Moving peptide science beyond chemical synthesis strategies and into the realms of peptide biology and therapeutics, it presents the overall contribution that peptide science has made to molecular, cellular, and whole organism biology, while also discussing future targets and therapeutic applications. Beneficial for Experts and Novices Alike Part I provides details of bioactive peptides that interact with common drug targets and analyzes some of the most competitive areas of current research worldwide. While it is widely known that mammalian physiological systems utilize bioactive peptides that have yet to be discovered, other animals provide a rich and valuable source of bioactive peptides. This fascinating area of science is the theme of Part II. Parts III and IV investigate the unique bioactivities of various peptides that are ripe for further exploration. This definitive reference also includes: A detailed description and analysis of a broad range of peptides that interact with G protein-coupled receptors, the quantitatively dominant drug target A discussion of non-ribosomal peptides, which hold promise as sources of endogenous mediators Important examples of common methodologies employed to identify, characterize, and further develop bioactive peptides from a range of natural sources With mounting worldwide interest in their therapeutic potential, bioactive peptides-includ

This brief introduces the structural and functional characterization of this important group of proteins. The content of each chapter is aimed at the non-specialist so that key concepts, methodologies and applications can be presented in a "snapshot" style volume. Multiheme cytochromes are ever more important now that it is possible to obtain genome sequences of microorganisms which have major biotechnological and environmental implications. There is a tremendous profusion of multiheme cytochromes which have great potential as targets for bioremediation and bioenergy applications. This brief gives a glimpse of an intriguing and fast-moving field.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This work establishes linear-scaling density-functional theory (DFT) as a powerful tool for understanding enzyme catalysis, one that can complement quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics simulations. The thesis reviews benchmark studies demonstrating techniques capable of simulating entire enzymes at the ab initio quantum-mechanical level of accuracy. DFT has transformed the physical sciences by allowing researchers to perform parameter-free quantum-mechanical calculations to predict a broad range of physical and chemical properties of materials. In principle, similar methods could be applied to biological problems. However, even the simplest biological systems contain many thousands of atoms and are characterized by extremely complex configuration spaces associated with a vast number of degrees of freedom. The development of linear-scaling density-functional codes makes biological molecules accessible to quantum-mechanical calculation, but has yet to resolve the complexity of the phase space. Furthermore, these calculations on systems containing up to 2,000 atoms can capture contributions to the energy that are not accounted for in QM/MM methods (for which the Nobel prize in Chemistry was awarded in 2013) and the results presented here reveal profound shortcomings in said methods.

This succinct volume addresses the production of inactive, potentially toxic proteins in the absence of correct protein folding and the resultant neurodegenerative diseases. Other topics include intrinsic disorder in protein structure and function and the effects of molten globules on protein toxicity. This concise and yet thorough text also discusses using toxin structure as a model for studying structural and functional aspects of protein chemistry. Protein Toxins in Modeling Biochemistry, a SpringerBrief, is essential reading for advanced researchers, scientists and advanced graduate students interested in protein chemistry and related areas of biochemistry and molecular science.

Based upon a workshop entitled “The Small HSP World� held in Québec 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.

Proteins are the cell's workers, their messengers and overseers. In these roles, proteins specifically bind small molecules, nucleic acid and other protein partners. Cellular systems are closely regulated and biologically significant changes in populations of particular protein complexes correspond to very small variations of their thermodynamics or kinetics of reaction. Interfering with the interactions of proteins is the dominant strategy in the development of new pharmaceuticals. Protein Ligand Interactions: Methods and Applications, Second Edition provides a complete introduction to common and emerging procedures for characterizing the interactions of individual proteins. From the initial discovery of natural substrates or potential drug leads, to the detailed quantitative understanding of the mechanism of interaction, all stages of the research process are covered with a focus on those techniques that are, or are anticipated to become, widely accessible and performable with mainstream commercial instrumentation. 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 notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Protein Ligand Interactions: Methods and Applications, Second Edition serves as an ideal guide for researchers new to the field of biophysical characterization of protein interactions - whether they are beginning graduate students or experts in allied areas of molecular cell biology, microbiology, pharmacology, medicinal chemistry or structural biology.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Addressing the increased use of protein and peptide candidates as treatments for previously untreatable diseases, this comprehensive and progressive source provides the reader with a roadmap to an increased understanding of issues critical for successfully developing a protein or peptide therapeutic candidate. Proteins and Peptides is an invaluable source for drug discovery and development scientists in the biopharmaceutical industry who frequently navigate the maze of protein and peptide pharmacokinetics, pharmacodynamics, and metabolism. Key features include: issues related to delivery of protein and peptide therapeutics in elderly populations and pharmacogenomics lessons learned on the major marketed areas of proteins and peptides, including interleukins, interferons, growth factors, and peptide hormones innovations for protein and peptide delivery such as needle-less delivery strategies for delivery of these molecules to locations such as the eye and brain generic issues of proteins and peptides

Receptor Tyrosine Kinases: Methods and Protocols explores on the most widely studied of the protein classes, known for their central role in several cellular functions and in a variety of human pathologies. Beginning with a section on activation and signaling of Receptor Tyrosine Kinases (RTKs), the book continues with chapters on aberrant expression of RTKs, trafficking and negative regulation, as well as RTKs as pharmacological targets. 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, laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Receptor Tyrosine Kinases: Methods and Protocols contains an up-to-date overview of the most relevant and widely used methods employed in this field, providing detailed protocols that molecular and cellular biologists could easily adopt in their research programs on RTKs.

Plant Proteomics: Methods and Protocols, Second Edition presents recent advances made in the field of proteomics and their application to plant biology and translational research. In recent years, improvements in techniques and protocols for high-throughput proteomics have been made at all workflow stages, from wet (sampling, tissue and cell fractionation, protein extraction, depletion, purification, separation, MS analysis, quantification) to dry lab (experimental design, algorithms for protein identification, bioinformatics tools for data analysis, databases, and repositories). Divided into nine convenient sections, chapters cover topics such as applications of gel-free, label- or label-free, imaging and targeted approaches to experimental model systems, crops and orphan species, as well as the study and analysis of PTMs, protein interactions, and specific families of proteins, and finally proteomics in translational research. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Plant Proteomics: Methods and Protocols, Second Edition seeks to serve both professionals and novices looking to exploit the full potential of proteomics in plant biology research.

Photoswitching Proteins: Methods and Protocols, focuses on proven applications of photoswitching proteins in cell and neurobiology. Optical approaches have been mostly embraced by the neurosciences to allow fast, high-resolution characterization and manipulation of single cells in complex neuronal tissue. These tools, including photoswitching of proteins, are now successfully used in almost all fields of biological research. 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.Comprehensive and practical, Photoswitching Proteins: Methods and Protocols highlights many of the possibilities for research based on light-inducible, high-resolution manipulation of biological systems.

This book provides a detailed description and analysis of the reduction and metabolism of metals and metalloids by sulfate reducing bacteria. The molecular mechanisms of bacterial resistance to copper are examined as well as extracellular electron transfer and bacterial metal oxide respiration. Furthermore, in this book enrichment, isolation, and physiology of magnetotactic bacteria are discussed.  The interactions of bacteria with metals in natural environments and their role in metal cycling have been studied for decades. Advances in studies of bacteria-metal interactions identified numerous important aspects of these interactions, such as bioremediation of metal-contaminated environments, the role of metals in redox reactions and other cellular functions, as well as the role of metals in toxicity and infection. Microbiologists, environmental scientists, and students interested in microbe interactions with metals and their effect on the environment and their application in biotechnology will be interested in the topics discussed in the book.

Enzyme Technology is one the most promising disciplines in modern biotechnology. In this book, the applications of a wide variety of enzymes are highlighted. Current studies in enzyme technology are focused towards the discovery of novel enzymes (termed "bio-discovery" or "bio-prospecting") and the identification and elucidation of novel pathways of these novel enzymes with emphasis on their industrial relevance. With the development of molecular techniques and other bioinformatics tools, the time to integrate this subject with other fields in the life sciences has arrived. A rapid expansion of the knowledge base in the field of enzyme biotechnology has occurred over the past few years. Much of this expansion has been driven by the bio-discovery of many new enzymes from a wide range of environments, some extreme in nature, followed by subsequent protein (enzyme) engineering. These enzymes have found a wide range of applications, ranging from bioremediation, bio-monitoring, biosensor development, bioconversion to biofuels and other biotechnologically important value-added products. Hydrolases constitute a major component of the global annual revenue generated by industrial enzymes and the emphasis has therefore been placed on these enzymes and their applications. With the immense interest of researchers active in this area, this book will serve to provide information on current aspects in this field of study. In the current edition, the contributions of many diversified topics towards establishing new directions of research in the area of enzyme biotechnology are described. This book serves to provide a unique source of information to undergraduates, post graduates and doctoral courses in microbiology and biotechnology along with allied life sciences. The present edition of the book covers all important areas of enzyme biotechnology i.e. the wide variety of enzymes in the field of enzyme biotechnology and their industrial applications, new methods and state-of-the-art information on modern methods of enzyme discovery. This book will act as good resource on most of the current facets of enzyme technology for all students engaged in bioengineering and biotechnology.

Cell-free protein expression promises to narrow the technological gap between DNA and protein technologies and provide a platform for broad application of synthetic biology principles in the Life Sciences. It is a rapid and high throughput methodology for the conversion of DNA encoded genetic information into protein-mediated biochemical activities. Cell-Free Protein Synthesis: Methods and Protocols brings together the key opinion leaders of cell-free technology development and provides case studies and detailed protocols for the application of cell-free methodology. Chapters cover the main directions in the development of cell-free technologies including several recently developed cell-free systems, as well as a number of applications of cell-free systems ranging from discovery of biofuel enzymes to in vitro assembly of viruses. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Cell-Free Protein Synthesis: Methods and Protocols seeks to serve a wide variety of scientists with its well-honed methodologies.

Featuring a diverse array of model organisms and scientific techniques, Sirtuins: Methods and Protocols collects detailed contributions from experts in the field addressing this vital family of genes. Opening with methods to generate sirtuin biology tools, the book continues by covering methods to identify sirtuin substrates, to measure sirtuin activity, and to study sirtuin biology. 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. Comprehensive and easy to use, Sirtuins: Methods and Protocols presents detailed protocols for sirtuin research that can be followed directly or modified to investigate new areas of sirtuin biology.

Chemokines constitute a large family of structurally similar cytokines that contain a signature of conserved cysteine residues joined by disulfide bridges. Binding of chemokines to specific G protein-coupled receptors followed by downstream signaling defines their biological function. Initially, chemoattraction was the key function linked to chemokines/chemokine receptors; however, in recent years, it has become clear that chemokine ligand-receptor interactions can also modulate cellular activation, survival, and proliferation, among other functions in homeostatic and diseased states. Importantly, major advances in our understanding of chemokine biology have led to chemokine receptors becoming specific therapeutic targets with great potential. In Chemokines: Methods and Protocols, expert researchers provide practical information regarding experimental models and state of the art protocols used to delineate chemokine/chemokine receptor function and their applications in health and disease. 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. Practical and easy to use, Chemokines: Methods and Protocols aims to reveal key protocols of functional and descriptive chemokine ligand/receptor assays that will be of practical significance to graduate students, post-doctoral fellows, trainees, and researchers in academia and industry.

In this acclaimed thesis, Eva Maria Huber reveals ground-breaking results by elucidating the crystal structure of the murine immunoproteasome in complex with a selective inhibitor. Huber does this by performing multidisciplinary methodologies including X-ray crystallography, fluorescence spectroscopy and mutagenesis experiments. Her exceptional results explore the immunoproteasome complex structures and are of outstanding importance for future scientific research especially in the pharmaceutical industry. These results will enable the functional analysis of individual proteasome subunits and support the development of novel drugs for autoimmune diseases such as multiple sclerosis or rheumatoid arthritis.

Providing current diverse approaches and techniques used to study the immunoproteome, Immunoproteomics: Methods and Protocols collects chapters from key researchers that deliver information to be used in diagnostics, disease progression, and vaccine correlates of protection analysis, to name but a few. This detailed volume includes techniques used for the study of the antibody targets of bacterial pathogens, viruses, and cancer, mass spectrometry-based approaches to characterize T-cell epitopes, chapters on detection and relative quantification of cytokines in serum, as well as in silico prediction of epitopes using sequence-based or modeling approaches. 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. Practical and thorough, Immunoproteomics: Methods and Protocols aids researchers in transferring these techniques to their own laboratories in addition to providing a reference to guide researchers toward appropriate techniques.

A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.

Colorectal cancer has for more than two decades served as the paradigm for the multi-step concept of cancer initiation and progression. Perhaps more than any other organ site, cancer of the colon is extensively characterized at the molecular level. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. The book will focus on the progression from the identification of mutations that drive colorectal cancer initiation and progression to the search for novel therapies to treat the disease.

Long non-coding RNAs (lnc)RNAs have emerged as a new paradigm in epigenetic regulation of the genome. Thousands of lncRNAs have been identified and observed in a wide range of organisms. Unlike mRNA, lncRNA have no protein-coding capacity. So, while their function is not entirely clear, they may serve as key organizers of protein complexes that allow for higher order regulatory events. Discovering these functions has been the result of intense research done of the last few years, and lncRNA research has had several critical developments during that time. This book will consolidate these ideas and models to better examine the most important issues in lncRNA biology. This will include critical studies that have led to the discovery and annotation of lncRNAs in numerous species, and the molecular mechanisms for a few lncRNA that have begun to emerge.

Cellular adhesion is a fundamental process that influences numerous biological activities such as morphogenesis, cell motility and division, as well as signalling. In addition, adhesion is a process important not only in normal physiology and development, but also in disease states such as tumourigenesis, cardiovascular disease, inflammation and infection. There are a plethora of proteins involved in adhesion-related events with a huge diversity in function. As a result, a wide variety of techniques exist to study adhesion related proteins and processes. In Adhesion Protein Protocols, Third Edition, chapters cover techniques to gain insight into the complex and incompletely understood processes that are involved in cellular adhesion. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Adhesion Protein Protocols, Third Edition will be useful for both those new to the field of adhesion protein research as well as the more experienced scientist.

The lipid-rich and otherwise challenging nature of many key tissues complicates many aspects of current research, and applications of the unique nature of lipoproteins and their biological effects has engendered unique and vital methodologies. In Lipoproteins and Cardiovascular Disease: Methods and Protocols, experts in the field present a compendium of advanced and classical molecular biology methods targeted towards lipoprotein, atherosclerosis, and vascular biology research, bringing together in a single volume an updated set of protocols and strategies for methods now driving the most recent advances, along with classical methods that are still widely used. Among the many topics covered in this cutting-edge work, the book delves into crucial techniques such as quantitative real-time PCR, microarrays, RT-PCR laser capture microdissection, and tissue-specific gene overexpression, knockout, and knockdown methodologies, including AAV as a liver-directed gene delivery vehicle. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and valuable notes which highlight tips on troubleshooting and avoiding known pitfalls. Comprehensive and easy to use, Lipoproteins and Cardiovascular Disease: Methods and Protocols serves both novices and experts alike as a complete guide for any researcher with an interest in lipoproteins and their significant biological effects.