This volume provides an overview of the current successes as well as pitfalls and caveats that are hindering the design of membrane proteins. Divided into six parts, chapters detail membrane transporter, FoldX force field, protein stability, G-Protein Coupled Receptors (GPCR) structures, transmembrane helices, membrane molecular dynamics (MD) simulations, pH-dependent protonation states, membrane permeability, and passive transport. 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, Computational Design of Membrane Proteins aims to ensure successful results in the further study of this vital field. Chapter 4 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

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.

Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the role of chemokines in the tumor microenvironment. Each chapter focuses on the chemokines patterns of expression, their regulation, and their roles in immune cell recruitment, as well as how they affect cancer immunity and tumorigenesis.Taken alongside its companion volumes, Tumor Microenvironment: The Role of Chemokines - Part B updates us on what we know about various aspects of the tumor microenvironment, as well as apprises us on future directions in the field. This book is essential reading for advanced cell biology and cancer biology students as well as scientists seeking an update on recent developments and research in the tumor microenvironment.

This thorough book collects methods and strategies to analyze proteomics data. It is intended to describe how data obtained by gel-based or gel-free proteomics approaches can be inspected, organized, and interpreted to extrapolate biological information. Organized into four sections, the volume explores strategies to analyze proteomics data obtained by gel-based approaches, different data analysis approaches for gel-free proteomics experiments, bioinformatic tools for the interpretation of proteomics data to obtain biological significant information, as well as methods to integrate proteomics data with other omics datasets including genomics, transcriptomics, metabolomics, and other types of data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detailed implementation advice that will ensure high quality results in the lab. Authoritative and practical, Proteomics Data Analysis serves as an ideal guide to introduce researchers, both experienced and novice, to new tools and approaches for data analysis to encourage the further study of proteomics. Chapter 16 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Protein engineering is the rational modification or redesign of proteins using genetic engineering. Thus, it is now possible to modify enzyme specificities, remodel antibodies, and redesign many multi-domain proteins for therapeutic purposes. While the procedures for the introduction of mutations have become routine, predicting and understanding the effects of these mutations can be complicated. This volume provides a comprehensive guide to the methods used at every stage of the engineering process, from the choice of mutation strategy, through protein stability studies, to critical evaluations of mammalian, yeast, and bacterial host expression systems. Protein Engineering: A Practical Approach is the first practical guide to this fascinating mixture of molecular biology, protein structure analysis, computation, and biochemistry. It combines a thorough theoretical foundation with detailed protocols and will be invaluable to all research workers in the area, from graduate students to senior investigators.

This book focuses on both high-density lipoproteins (HDL) metabolism and related diseases from the perspectives of the world-class experts in HDL. Several chapters in this book provide the overall information about HDL metabolism via detailed discussion of HDL structures as well as several key molecules involved in its functions, such as SR-B1 and Cholesteryl Ester Transfer Protein Inhibitors and so on. The rest of this book illustrates the connection between HDL and several diseases that are the major concerns of people's health in many countries, and devotes to exploring the therapies of HDL related diseases. With a better understanding of the HDL metabolism and diseases, this book will benefit the audiences with interest in HDL from biomedicine to clinical practice.

This second edition provides new and updated methods on the principles underlying modern protein analysis, from statistical issues to gel-based and mass spectrometry-based applications. Chapters detail protein quantification as basis for realisation of quantitative studies, gel-based and mass spectrometry-based quantification techniques, TMT, IPTL, PRM, MALDI Imaging, SILAC, PTM analysis, DIA, cross-linking, and the up-to-date topics of software and data analysis. 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, Quantitative Methods in Proteomics, Second Edition aims to provide comprehensive and competent overview in the important and still growing field of quantitative proteomics.

This volume compiles new experimental approaches and concepts focusing mostly, but not solely, on ways to manipulate and regulate Ras activity and its downstream signaling output. Chapters detail standard methodologies, biochemical methods, Ras processing trafficking and localization, Ras signaling and inhibition, and in vivo models for studying Ras function. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, application details for both the expert and non-expert reader, and tips on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Ras Activity and Signaling: Methods and Protocols aims to provide support and guidance to lab workers in their work on Ras GTPases and in the design of new projects requiring novel methodologies.

Translational Urinomics provides an overview of urine analysis using proteomics, metabolomics, transcriptomics or any combination thereof for the diagnosis and prognosis of diseases related to the urinary system and the kidneys. The text approaches urine biomarkers from a new perspective, incorporating up-to-date studies of mass-spectrometry-based biomarker discovery as well as the latest advances in personalized medicine. The integration of technology-driven techniques, such as OMICS also provides a unique opportunity for improved diagnostics accuracy of urinary-related diseases. For nephrologists and urologists looking for new approaches to well-known problems, this edited volume serves as a valuable guide.

This book reviews the latest trends in glycobiotechnology, it offers an authoritative discussion about future directions of glycoengineering, and it provides a comprehensive overview about the current and emerging approaches to identify, quantify and characterize glycosylated proteins. Divided into 14 chapters, the book outlines recombinant glycoprotein expression in mammalian cells, insect cells, yeast, and bacterial systems. It covers the chemical and enzymatic syntheses of glycans and glyconjugates, and addresses the impact of glycosylation on protein function for the development of biologicals including vaccines. In the final chapters of the book, readers will discover more about the state-of-the-art in glycomics, glycoproteomics and glycan array technologies.

This volume provides a comprehensive set of protocols that can be used by any research lab to investigate diverse functional and structural properties of Single Stranded DNA Binding Proteins (SSBs) from eubacterial, archaeal, eukaryotic, mitochondrial and viral systems. 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, Single Stranded DNA Binding Proteins aims to be a useful practical guide to researchers to help further their study in this field.

The book Heat Shock Proteins in Cancer Therapeutics provides the most comprehensive review on contemporary knowledge on the role of HSP in various types of cancer therapeutics. Using an integrative approach, the contributors provide a synopsis of the most current updates on the state of HSP in cancer therapeutics. The heat shock response pathway is a highly conserved cellular process. Heat shock factors are a master transcriptional regulator responsible for expression of several important heat shock proteins, which can effectively protect critical client proteins from misfolding and degradation, thus maintaining intracellular integrity under stressed conditions. Recent studies have demonstrated the direct connections between heat shock response players and tumor cell survival, validating heat shock response players as novel molecular targets in anticancer treatment. Although many hurdles in clinical application still need to be effectively addressed, such as undesirable drug toxicity and off target effects; narrow therapeutic window; poor PK/PD profiles, etc. Recent reports on synergistic drug combination, advanced prodrug design, smart nanoparticle packaging, and RNA aptamer selection offer promising solutions to overcome these challenges. Future advancements in this fast-growing area can potentially lead to the next generation of cancer therapeutics. Key basic and clinical research laboratories from major universities, academic medical hospitals, biotechnology and pharmaceutical laboratories around the world have contributed chapters that review present research activity and importantly project the field into the future. The book is a must read for graduate students. medical students, basic science researchers and postdoctoral scholars in the fields of Cancer Biology, Oncology, Translational Medicine, Clinical Research, Biotechnology, Cell & Molecular Medicine, Pharmaceutical Scientists and Researchers involved in Drug Discovery.

The origin of life has been investigated by many researchers from various research fields, such as Geology, Geochemistry, Physics, Chemistry, Molecular Biology, Astronomy and so on. Nevertheless, the origin of life remains unsolved. One of the reasons for this could be attributed to the different approaches that researchers have used to understand the events that happened on the primitive Earth. The origins of the main three members of the fundamental life system, as gene, genetic code and protein, could be only separately understood with these approaches. Therefore, it is necessary to understand the origins of gene, the genetic code, tRNA, metabolism, cell structure and protein not separately but comprehensively under a common concept in order to understand the origin of life, because the six members are intimately related to each other. In this monograph, the author offers a comprehensive hypothesis to explain the origin of life under a common concept. At the same time, the author offers the [GADV] hypothesis contrasting it with other current hypotheses and discusses the results of analyses of genes/proteins and the experimental data available in the exploration of the current knowledge in the field. This book is of interest for science students, researchers and the general public interested in the origin of life.

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 21 presents eight review chapters authored by experts in the related fields. The first chapter covers the enzyme squalene monooxygenase and lipid levels and its relevance in health and disease. Chapter two presents a systematic analysis of the structural and functional aspects of heteromeric solute carriers. The third chapter provides a review of the role of CI- in type IV collagen assembly, function, and disease, including future directions for studies. This is followed by a summary in chapter four about the recent progress on defining the roles of the Slit-Robo signaling in bone metabolism and the possible roles of the interaction between Robo and neural epidermal growth factor-like proteins. Chapter five discusses recent data about the evolutionary aspects on structural differences between humans and the nematode in relation to previous knowledge of core proteins and GAG-attachment sites in Chn and CS proteoglycans of C.elegans and humans. The sixth chapter summarizes the immunochemical character of the IGHV1-69-derived RFs and the recognition mechanism of the IGHV1-69-derived RFs. Chapter seven covers regulated alternative translocation and its role as an emerging mechanism to regulate transmembrane proteins. Finally, chapter eight reviews current progress on IL-36 protein and biology and novel investigative tools. 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 edition details a collection of specific shotgun proteomics-based laboratory techniques and applications developed in leading laboratories and proteomics units worldwide. Chapters cover a broad range of topics covering, shotgun proteomics of extracellular vesicles and subcellular structures, shotgun proteomics in non-model organisms, clinical proteomics, food proteomics, analysis of post-translational modifications and protein complexes, and data processing and storage. 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, Shotgun Proteomics: Methods and Protocols aims to be an up-to-date guide for researchers seeking to understand the proteome of any given biological sample.

This book reviews the principles of design and examples of successful implementation of proteinkinase inhibitors (PKI), and offers a comprehensive and authoritative overview of the history and latest developments in the field. Chapters written by experts from industry and academia cover the function, structure and topology of Proteinkinases, molecular modelling, disclose how to achieve high level of selectivity for kinase inhibitors, and exploit kinase inhibitors for cancer treatment. Particular attention is given to Inhibitors of c-Jun N-terminal kinase 3, and to covalent Janus Kinase 3 Inhibitors. A case study on Receptor Tyrosine Kinases EGFR, VEGFR, PDGFR is also presented in this book. Given its breath, this book will appeal to medicinal chemists, students, researchers and professionals alike.

This book focuses on the development of stapled peptides, a novel molecular modality used to regulate aberrant intracellular protein-protein interactions (PPIs). The author designs and presents a novel helical peptide stabilization methodology by constructing a chiral cross-linker moiety, namely "chiral center induced peptide helicity (CIH)". The book demonstrates that a precisely positioned carbon chiral center on tether can decisively determine the secondary structure of a peptide, and that the R-configured peptide is helical, while the S-configured peptide is non-helical. Further, it reports that helicity-enhanced R isomer peptides displayed significantly enhanced cell permeability and target binding affinity, as well as tumor inhibition efficiency, in comparison to S isomer peptides. The book will not only advance readers' understanding of the basic principle of stapled peptides, but also accelerate the clinical transformation of stapled peptide drugs.

This book reviews current understanding of the biological roles of extracellular molecular chaperones. It provides an overview of the structure and function of molecular chaperones, their role in the cellular response to stress and their disposition within the cell. It also questions the basic paradigm of molecular chaperone biology - that these proteins are first-and-foremost protein-folding molecules. The current paradigms of protein secretion are reviewed and the evolving concept of proteins (such as molecular chaperones) as multi-functional molecules for which the term 'moonlighting proteins' has been introduced is discussed. The role of exogenous molecular chaperones as cell regulators is examined and the physiological and pathophysiological role that molecular chaperones play is described. In the final section, the potential therapeutic use of molecular chaperones is described and the final chapter asks the question - what does the future hold for the extracellular biology of molecular chaperones?

This detailed new edition presents the latest developments of the main pillars of protein analysis, namely sample preparation, separation, and characterization. Core areas in this volume are protocols for the analysis of post-translational modifications and protein interaction partners, followed by sophisticated procedures to enrich for extracellular vesicles and organelles, along with several types of protein immuno-assays complemented by various methods for the characterization of antibodies and host-cell protein analysis. Last but not least, a few standard sample preparation protocols and recent advances concerning immuno-chemical detection of proteins are included as well. 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 up-to-date, Proteomic Profiling: Methods and Protocols, Second Edition serves as an ideal reference for students of biochemistry, biomedicine, biology, and genomics and will be an invaluable source for the experienced, practicing scientist as well.

This book presents various computer-aided drug discovery methods for the design and development of ligand and structure-based drug molecules. A wide variety of computational approaches are now being used in various stages of drug discovery and development, as well as in clinical studies. Yet, despite the rapid advances in computer software and hardware, combined with the exponential growth in the available biological information, there are many challenges that still need to be addressed, as this book shows. In turn, it shares valuable insights into receptor-ligand interactions in connection with various biological functions and human diseases. The book discusses a wide range of phylogenetic methods and highlights the applications of Molecular Dynamics Simulation in the drug discovery process. It also explores the application of quantum mechanics in order to provide better accuracy when calculating protein-ligand binding interactions and predicting binding affinities. In closing, the book provides illustrative descriptions of major challenges associated with computer-aided drug discovery for the development of therapeutic drugs. Given its scope, it offers a valuable asset for life sciences researchers, medicinal chemists and bioinformaticians looking for the latest information on computer-aided methodologies for drug development, together with their applications in drug discovery.

This volume explores the basic issues of "allostery" and "network" that are fundamental to studying this field. Chapters in this book look at how the basic "machine-like" proteins, that are similar to "human machines," need to be organized, architecturally, to relate to different organizational layers. Chapters cover topics such as methodological/computational factors focused on links between allostery and network formalism; the presence of oscillating modes transversing the structure and underlying network wiring of the allosteric process; the "action at distance" by transduction of signals across an organized network structure; and the P53 protein located at the cross-road of cell cycle regulation, genome integrity, and cancer development. 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. Thorough and practical, Allostery: Methods and Protocols is a valuable resource for any scientists and researcher interested in learning more about this developing field.

This book discusses the unique ion channels and transporters found within the epithelial tissues of various organs, including the kidney, intestine, pancreas and respiratory tract. Authors focus on demonstrating the crucial roles that each of these channels and transporters play in transepithelial ion and fluid transport across epithelia, as well as in maintaining homeostasis. It allows readers to gain an understanding of the fundamentals of ion transport, in terms of function, modelling, regulation, trafficking, structure and pharmacology. This is the second of three volumes highlighting the importance of epithelial ion channels and transporters in basic physiology and pathophysiology of human diseases. This volume focuses on a wide array of epithelial tissues and the use of organoids to study epithelial function. Furthermore, clinical researchers and basic scientists from various fields provide a medical perspective on the physiology of a number of tissues and organs of the body including the pancreas, intestine, sweat glands, mammary gland, inner ear epithelia, retinal pigment epithelia of the eye, choroid plexus, and the ectodermal epithelia in dental enamel formation. This volume aims to 'round out' the reader's journey from basic science to the laboratory bench and clinical management of molecular diseases, making Volume 2 a must-read for students and scientists in the field of physiology, as well as for clinicians.

The new series "Microbiology Monographs" begins with two volumes on intracellular components in prokaryotes. In this first volume, "Inclusions in Prokaryotes", the components, labeled inclusions, are defined as discrete bodies resulting from synthesis of a metabolic product. Research on the biosynthesis and reutilization of the accumulated materials is still in progress, and interest in the inclusions is growing. This comprehensive volume provides historical background and comprehensive reviews of eight well-known prokaryotic inclusions.

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. Chapter "Stationary and Non-Stationary Ion- and Water Flux Interactions in Kidney Proximal Tubule. Mathematical Analysis of Isosmotic Transport by a Minimalistic Model" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book provides an overview of the biology and biochemistry of peroxisomes, and discusses the contribution of these organelles to peroxisomal and neurodegenerative diseases. It begins with a detailed introduction to the biogenesis and metabolic functions of peroxisomes, and highlights their role in oxidative stress and in lipid metabolism such as fatty acid oxidation. The following chapters focus on the molecular and clinical aspects of peroxisomal disorders caused by defects in peroxisomal function. In particular, the biological aspects of peroxisomal biogenesis disorders such as Zellweger syndrome and Heimler syndrome are discussed. This includes their underlying genetic causes as well as the biochemical and metabolic defects associated with the disorders. In addition, several chapters cover recent observations suggesting an association between peroxisomal dysfunction and neurodegenerative diseases such as Alzheimer's, Multiple Sclerosis and other degenerative cerebellar pathologies. The final section of the book discusses important cell and animal models for studying the role of peroxisomes in human diseases and presents current therapeutic strategies for their treatment. This book deals with a highly topical subject that is at the heart of current research, and represents a valuable contribution for all students and researchers who want to understand the complex biology of peroxisomes and their role in human diseases.