This book is devoted to the physical and mathematical modeling of the formation of complexes of protein molecules. The models developed show remarkable sensitivity to the amino acid sequences of proteins, which facilitates experimental studies and allows one to reduce the associated costs by reducing the number of measurements required according to the developed criteria. These models make it possible to reach a conclusion about the interactions between different amino acid chains and to identify more stable sites on proteins. The models also take the phosphorylation of amino acid residues into account. At the end of the book, the authors present possible directions of application of their physical and mathematical models in clinical medicine.

This book introduces characteristic features of the protein structure prediction (PSP) problem. It focuses on systematic selection and improvement of the most appropriate metaheuristic algorithm to solve the problem based on a fitness landscape analysis, rather than on the nature of the problem, which was the focus of methodologies in the past. Protein structure prediction is concerned with the question of how to determine the three-dimensional structure of a protein from its primary sequence. Recently a number of successful metaheuristic algorithms have been developed to determine the native structure, which plays an important role in medicine, drug design, and disease prediction. This interdisciplinary book consolidates the concepts most relevant to protein structure prediction (PSP) through global non-convex optimization. It is intended for graduate students from fields such as computer science, engineering, bioinformatics and as a reference for researchers and practitioners.

This new edited volume in the Springer Subcellular Biochemistry Series presents a comprehensive, state-of-the-art overview of the proteomics of peroxisomes derived from mammalian, Drosophila, fungal, and plant origin, and contains contributions from leading experts in the field. The development of sensitive proteomics and mass spectrometry technologies, combined with bioinformatics approaches now allow the identification of low-abundance and transient peroxisomal proteins and permits to identify the complete proteome of peroxisomes, with the consequent increase of our knowledge of the metabolic and regulatory networks of these important cellular organelles. The book lines-up with these developments and is organized in four sections including: (i) mass spectrometry-based organelle proteomics; (ii) prediction of peroxisomal proteomes; (iii) analysis of peroxisome proteome interaction networks; and (iv) peroxisomes in relation to other subcellular compartments. The editor Luis A. del Rio is Professor ad honorem of the Spanish National Research Council (CSIC) in the Group of Antioxidants, Free Radicals and Nitric Oxide in Biotechnology, Food and Agriculture, Department of Biochemistry and Cell & Molecular Biology of Plants, at the Estacion Experimental del Zaidin, Granada, Spain. Del Rio's research group focuses on the metabolism of reactive oxygen species (ROS), reactive nitrogen species (RNS) and antioxidants in plant peroxisomes, and the ROS- and RNS-dependent role of peroxisomes in plant cell signalling. The editor Michael Schrader is Professor of Cell Biology & Cytopathology in the Department of Biosciences at the University of Exeter, UK. Using mammalian peroxisomes as model organelles, Prof. Schrader and his team aim to unravel the molecular machinery and signalling pathways that mediate and regulate the formation, dynamics and abundance of these medically relevant cellular compartments.

This book comprehensively reviews the state-of-the-art strategies developed for protein-protein interaction (PPI) inhibitors, and highlights the success stories in new drug discovery and development. Consisting of two parts with twelve chapters, it demonstrates the design strategies and case studies of small molecule PPI inhibitors. The first part discusses various discovery strategies for small molecule PPI inhibitors, such as high throughput screening, hot spot-based design, computational approaches, and fragment-based design. The second part presents recent advances in small molecule inhibitors, focusing on clinical candidates and new PPI targets. This book has broad appeal and is of significant interest to the pharmaceutical science and medicinal chemistry communities.

The Subcellular Biochemistry series has recently embarked upon an almost encyclopaedic coverage of topics relating to the structure and function of macromolecular complexes (Volumes 82, 83 and 87). The present multi-author text covers numerous aspects of current research into molecular virology, with emphasis upon viral protein and nucleoprotein structure and function. Structural data from cryo-electron microscopy and X-ray crystallography is displayed throughout the book. The 17 chapters in the book cover diverse interesting topics, all currently under investigation, contributed by authors who are active actively involved in present-day research. Whilst structural aspects predominate, there is much consideration of the structure-function relationship. In addition, the book correlates with and extends from Volume 68 of the series "Structure and Physics of Viruses: An Integrated Textbook". This book is directed primarily at professionals that work in the broad field of Structural Biology and will be of particular interest to Structural Virologists. The editors, David Bhella and Robin Harris, have much experience in virology and protein structure, respectively. Dr Bhella is Director of the Scottish Macromolecular Imaging Centre. Professor Robin Harris is the long-standing Series Editor of the Subcellular Biochemistry series. He has edited and contributed to several books in the series.

Epigenetic mechanisms (DNA modifications, histone alterations and non-coding RNAs) are crucial for transcriptional regulation and alterations of the "physiological epigenome" are increasingly associated with human diseases. During the last decade the emerging field of neuroepigenomics have started to impact tremendously in areas such learning and memory, addiction or neurodegeneration. This expert volume covers the role of epigenetic molecular mechanism in regulation of central nervous system's function, one of the most exciting areas of contemporary molecular neuroscience. The book describes the current knowledge on the epigenetic basis of human disease covering the complete lifespan: from neurodevelopment/childhood (Rett Syndrome, Rubinstein-Taybi, autism), adolescence (eating disorders, drug addiction, anxiety), adulthood (depression, schizophrenia, amyotrophic lateral sclerosis, Huntington's disease) and elderly (Alzheimer's disease, Parkinson's disease). The book also covers the three major players on neuroepigenomic mechanisms: histones alterations, DNA modifications and non-coding RNAs, their roles at the molecular and cellular level and the impact of their alterations on neuronal function and behavior. Finally, a special chapter on state-of-the-art technologies helps the reader not only to understand epigenetic driven changes in human cognition and diseases but also the methodology that will help to generate paradigm shifts on our understanding of brain function and the role of the neuroepigenome in human diseases.

This textbook introduces the basics of protein structure and logically explains how to use online software to explore the information in protein structure databases. Readers will find easily understandable, step-by step exercises and video-trainings to support them in grasping the fundamental concepts. After reading this book, readers will have the skills required to independently explore and analyze macromolecular structures, will be versed in extracting information from protein databases and will be able to visualize protein structures using specialized software and on-line algorithms. This book is written for advanced undergraduates and PhD students wishing to use information from structural biology in their assignments and research and will be a valuable source of information for all those interested in applied and theoretical aspects of structural biology.

This book covers the latest developments in capillary electrophoresis-mass spectrometry for the analysis of therapeutic proteins. The application of capillary electrophoresis-mass spectrometry (CE-MS) coupling technology in the analysis of recombinant therapeutic proteins is detailed thoroughly. Specific topics include recent developments in coupling capillary electrophoresis with mass spectrometry for the quality control of monoclonal antibody therapeutics, top-down analysis of monoclonal antibody using the CE-MS platform, and detection of host cell protein impurities. Comprehensive characterization of antibody-drug conjugates (ADCs) by coupling capillary electrophoresis with mass spectrometry is also covered. This is an ideal book for scientists in the life science and biopharmaceutical industry who are working on characterizing the PTMs of monoclonal antibodies, as well as graduate students and researchers in the separation science and biological mass spectrometry fields.

Due to continuous technical developments and new insights into the high complexity of neurological diseases, there is an increasing need for the application of proteomic technologies which can yield potential biomarker readouts for improved clinical management as well as for the development of new drugs by struggling pharmaceutical companies. This book describes the step-by-step use of proteomic methods such as two-dimensional gel electrophoresis, multiplex immunoassay, liquid chromatography mass spectrometry (LC-MS) and selective reaction monitoring MS, to increase our understanding of these diseases, with the ultimate aim of improving patient care. The volume will be of high interest to clinical scientists, physicians and pharmaceutical company scientists as it gives insights into the latest technologies enabling the revolution of personalized medicine. It is of direct interest to both technical and bench biomarker scientists as it gives step by step instructions on how to carry out each of the protocols. It is also of interest to researchers as each technique will be presented in the context of a specific neurological disorder, including Alzheimer's disease, multiple sclerosis, autism spectrum disorders, schizophrenia, major depressive disorder and bipolar disorder. Finally, it will also highlight the future research efforts in this field, which are endeavoring to convert proteomic platforms to the form of hand held devices which can be used in a point of care setting and return diagnostic results within the timeframe of a visit to the general practitioner.

This volume provides methods for modern macromolecular crystallography, including all steps leading to crystal structure determination and 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 practical, Protein Crystallography aims to ensure successful results in the further study of this vital field.

Over the past decade, there has been an increase in powerful proteomics technologies that allow greater fundamental insights into the blood proteome. Further developments in informatic analyses, software developments, and computational tools are providing insights into large data sets, open-source data along with large-scale application of bioinformatics. Serum/Plasma Proteomics: Methods and Protocols, Second Edition is a comprehensive resource of protocols for areas, pre-analytical through to analytical, of plasma and serum proteomics. Divided into five convenient sections, covering fractionation strategies for in-depth blood proteome analysis, defined procedures for blood collection, handling and storage, detailed protocols for performing both antibody-based and non-antibody based quantitative assays, proteome analysis of blood cell compartments, circulating nanomebraneous vesicles and blood-related fluids, data management, statistical design, and bioinformatic challenges. 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 practical, Serum/Plasma Proteomics: Methods and Protocols, Second Edition delivers a valuable foundation for the development and application of blood-based proteomics, and further incorporates blood cell components, including platelets, red blood cells, circulating extracellular vesicles/exosomes, and related biofluids.

The series Topics in Current Chemistry Collections presents critical reviews from the journal Topics in Current Chemistry organized in topical volumes. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the 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

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. Volume 17 of Protein Reviews is the beginning of a new publication format. The volumes will appear online before they are published in a printed book. Articles will be 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. The chapters in this volume are authored by experts in the field. They deal with aspects of structure and biological activity of selected proteins. Specific chapters deal with the aggregation of FET proteins (FUS, EWSR1, TAF15) as a pathological change in amyotrophic lateral sclerosis, structural changes fundamental to gating of the cystic fibrosis transmembrane conductance regulator anion channel pore, the dual roles for epithelial splicing regulatory proteins 1 (ESRP1) and 2 (ESRP2) in cancer progression, controlling autolysis during flagella insertion in Gram-negative bacteria, the regulation of skeletal muscle myoblast differentiation and the proliferation by pannexins, hyaluronidase and chondroitinase, factors that control mitotic spindle elongation, how secreted phospholipase A2 type IIA (sPLA2-IIA) activates integrins in an allosteric manner, the simple and unique allosteric machinery of Thermus caldophilus lactate dehydrogenase, and the reduction of chemically stable multibonds: Nitrogenase-like biosynthesis of tetrapyrroles. This volume is intended for research scientists, clinicians, physicians, and graduate students in fields of biochemistry, cell biology, molecular biology microbiology, immunology and genetics.

This volume presents established bioinformatics tools and databases for function prediction of proteins. Reflecting the diversity of this active field in bioinformatics, the chapters in this book discuss a variety of tools and resources such as sequence-, structure-, systems-, and interaction-based function prediction methods, tools for functional analysis of metagenomics data, detecting moonlighting-proteins, sub-cellular localization prediction, and pathway and comparative genomics databases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, step-by-step instructions of how to use software and web resources, use cases, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Protein Function Prediction: Methods and Protocols is a valuable and practical guide for using bioinformatics tools for investigating protein function

This volume discusses protocols that cover genetic manipulation of Chinese hamster ovary (CHO) cells for recombinant protein production, and protocols for the characterization of CHO cells using 'omic approaches. This book also explores methods that discuss the genome editing tool, CRISPR/Cas9, and the characterization of recombinant protein products, such as glycosylation and host cell protein 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. Comprehensive and cutting-edge, Heterologous Protein Production in CHO Cells: Methods and Protocols is a valuable resource for scientists and researchers who are interested in further studying cell production in CHO cells.

This volume is a wide-ranging tool for studying protein-carbohydrate interactions that extend from traditional biochemical methods to state-of-the-art techniques. This book focuses on four different research themes: Part I describes methods for screening and quantifying CAZyme activity; Part II contains methods for investigating the interactions between proteins and carbohydrate ligands; Part III discusses methods for the visualization of carbohydrates and protein-carbohydrate complexes; and Part IV focuses on structural and "omic" approaches for studying systems of CAZymes. 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. Cutting-edge and thorough, Protein-Carbohydrate Interactions: Methods and Protocols is a valuable resource to the glycomics research community. In this continuously advancing field, the methods in this book highlight the biology of glycomics, thus driving biotechnological innovation and solutions for human health and sustainable resources within the emerging green community.

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 volume serves as a valuable handbook for the development of nanomedicines made of polymer nanoparticles because it provides researchers, students, and entrepreneurs with all the material necessary to begin their own projects in this field. Readers will find protocols to prepare polymer nanoparticles using different methods, since these are based on the variety of experiences that experts encounter in the field. In addition, complex topics such as, the optimal characterization of polymer nanoparticles is discussed, as well as practical guidelines on how to formulate polymer nanoparticles into nanomedicines, and how to modify the properties of nanoparticles to give them the different functionalities required to become an efficient nanomedicine for different clinical applications. The book also discusses the translation of technology from research to practice, considering aspects related to industrialization of preparation and aspects of regulatory and clinical development.

This volume covers an array of techniques available for studying peptide-protein docking and design. The book is divided into four sections: peptide binding site prediction; peptide-protein docking; prediction and design of peptide binding specificity; and the design of inhibitory peptides. The chapters in Modeling Peptide-Protein Interactions: Methods and Protocols cover topics such as the usage of ACCLUSTER and PeptiMap for peptide binding site prediction; AnchorDock and ATTRACT for blind, flexible docking of peptides to proteins; flexible peptide docking using HADDOCK and FlexPepDock; identifying loop-mediated protein-protein interactions using LoopFinder; and protein-peptide interaction design using PinaColada. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary details for successful application of the different approaches and step-by-step, readily reproducible protocols, as well as tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Modeling Peptide-Protein Interactions: Methods and Protocols provides a diverse and unified overview of this rapidly advancing field of major interest and applicability.

This volume provides the most commonly used methods and protocols to study the apoptotic and non-apoptotic roles of CD95. Chapters explore molecular, biochemical, cellular methods and animal models to in order to better understand the biological functions of this cytokine. 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 practical, CD95: Methods and Protocols aims to foster original research on CD95/CD95L couple.

The aim of the book is to discuss the application of molecular pathology in cancer research, and its contribution in the classification of different tumors and identification of potential molecular targets, as well as how this knowledge may be translated into clinical practice, and the huge impact this field is likely to have in the next 5 to 10 years.

Using a novel approach that combines high temporal resolution of the laser T-jump technique with unique sets of fluorescent probes, this study unveils previously unresolved DNA dynamics during search and recognition by an architectural DNA bending protein and two DNA damage recognition proteins. Many cellular processes involve special proteins that bind to specific DNA sites with high affinity. How these proteins recognize their sites while rapidly searching amidst ~3 billion nonspecific sites in genomic DNA remains an outstanding puzzle. Structural studies show that proteins severely deform DNA at specific sites and indicate that DNA deformability is a key factor in site-specific recognition. However, the dynamics of DNA deformations have been difficult to capture, thus obscuring our understanding of recognition mechanisms. The experiments presented in this thesis uncover, for the first time, rapid (~100-500 microseconds) DNA unwinding/bending attributed to nonspecific interrogation, prior to slower (~5-50 milliseconds) DNA kinking/bending/nucleotide-flipping during recognition. These results help illuminate how a searching protein interrogates DNA deformability and eventually "stumbles" upon its target site. Submillisecond interrogation may promote preferential stalling of the rapidly scanning protein at cognate sites, thus enabling site-recognition. Such multi-step search-interrogation-recognition processes through dynamic conformational changes may well be common to the recognition mechanisms for diverse DNA-binding proteins.

Recent work has begun to elucidate at the molecular level how albumin is handled by the kidney and how albuminuria develops in various proteinuric diseases including minimal change disease and focal segmental glomerulosclerosis. This volume provides a comprehensive overview of the renal handling of albumin - from basic mechanisms to the pathophysiology of proteinuric diseases. In describing the basic mechanisms of albuminuria, a particular highlight will be the focus on advanced imaging techniques such as intravital microscopy that have allowed a detailed "window" into albumin transit through the kidney. The volume will cover the epidemiological studies which show that albuminuria is a strong and independent marker of kidney disease progression and cardiovascular events, the molecular details of albumin handling in the kidney at the level of the glomerulus and the proximal tubule and the pathophysiology of proteinuric diseases including minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis and diabetic nephropathy.

Heat Shock Proteins and Plants provides the most up-to-date and concise reviews and progress on the role of heat shock proteins in plant biology, structure and function and is subdivided into chapters focused on Small Plant HSPs (Part I), Larger Plant HSPs (Part II) and HSPs for Therapeutic Gain (Part III). This book is written by eminent leaders and experts from around the world and is an important reference book and a must-read for undergraduate, postgraduate students and researchers in the fields of Agriculture, Botany, Crop Research, Plant Genetics and Biochemistry, Biotechnology, Drug Development and Pharmaceutical Sciences.