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.

A look at the methods and algorithms used to predict protein structure

A thorough knowledge of the function and structure of proteins is critical for the advancement of biology and the life sciences as well as the development of better drugs, higher-yield crops, and even synthetic bio-fuels. To that end, this reference sheds light on the methods used for protein structure prediction and reveals the key applications of modeled structures. This indispensable book covers the applications of modeled protein structures and unravels the relationship between pure sequence information and three-dimensional structure, which continues to be one of the greatest challenges in molecular biology.

With this resource, readers will find an all-encompassing examination of the problems, methods, tools, servers, databases, and applications of protein structure prediction and they will acquire unique insight into the future applications of the modeled protein structures. The book begins with a thorough introduction to the protein structure prediction problem and is divided into four themes: a background on structure prediction, the prediction of structural elements, tertiary structure prediction, and functional insights. Within those four sections, the following topics are covered: Databases and resources that are commonly used for protein structure predictionThe structure prediction flagship assessment (CASP) and the protein structure initiative (PSI)Definitions of recurring substructures and the computational approaches used for solving sequence problemsDifficulties with contact map prediction and how sophisticated machine learning methods can solve those problemsStructure prediction methods that rely on homology modeling, threading, and fragment assemblyHybrid methods that achieve high-resolution protein structuresParts of the protein structure that may be conserved and used to interact with other biomoleculesHow the loop prediction problem can be used for refinement of the modeled structuresThe computational model that detects the differences between protein structure and its modeled mutant

Whether working in the field of bioinformatics or molecular biology research or taking courses in protein modeling, readers will find the content in this book invaluable.

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.

Recent advances in protein structural biology, coupled with new developments in human genetics, have opened the door to understanding the molecular basis of many metabolic, physiological, and developmental processes in human biology. Medical pathologies, and their chemical therapies, are increasingly being described at the molecular level. For single-gene diseases, and some multi-gene conditions, identification of highly correlated genes immediately leads to identification of covalent structures of the actual chemical agents of the disease, namely the protein gene products. Once the primary sequence of a protein is ascertained, structural biologists work to determine its three-dimensional, biologically active structure, or to predict its probable fold and/or function by comparison to the data base of known protein structures. Similarly, three-dimensional structures of proteins produced by microbiological pathogens are the subject of intense study, for example, the proteins necessary for maturation of the human HIV virus. Once the three-dimensional structure of a protein is known or predicted, its function, as well as potential binding sites for drugs that inhibit its function, become tractable questions. The medical ramifications of the burgeoning results of protein structural biology, from gene replacement therapy to "rational" drug design, are well recognized by researchers in biomedical areas, and by a significant proportion of the general population. The purpose of this book is to introduce biomedical scientists to important areas of protein structural biology, and to provide an insightful orientation to the primary literature that shapes the field in each subject.
The chapters in this volume cover aspects of protein structural biology which have led to the recognition of fundamental relationships between protein structure and function.

Hereditary tyrosinemia type 1 (HT1), the most severe inborn error of the tyrosine degradation pathway, is due to a deficiency in fumarylacetoacetate hydrolase (FAH). The worldwide frequency of HT1 is one per 100,000 births, but some regions have a significantly higher incidence (1:1,800). The FAH defect results in the accumulation of toxic metabolites, mainly in the liver. If left untreated, HT1 is usually fatal before the age of two. HT1 patients develop several chronic complications including cirrhosis with a high risk of hepatocellular carcinoma (HCC) and neuropsychological impairment. Treatment comprises an inhibitor of the pathway, Nitisinone, a strict dietary treatment or liver transplantation. Early treatment is important to avoid HCC. The book includes the latest developments on the molecular basis of HT1, its pathology, screening and diagnosis and management of the disease written by leading scientists, geneticists, hepatologists and clinicians in the field.

This book covers structure, function, and important roles of the SH domains, structure-function relationships, the versatile nature of their action, mechanisms of aggregation, specificity of interactions, impact of mutations on protein functional dysregulation, and cell signaling. Their involvement in various cellular processes such as migration, invasiveness, actin reorganization, shaping spines, determination of the morphology assembly of fibrils, and mechanotransduction makes these molecules attractive drug targets. Substrates, inhibitors and activators of PTKs present a wide variety of therapeutic agents in the context of delivering treatments for numerous pathologies. The new emerging field of stem cell therapies and design of biomaterials for treatments relies on the directed regulation of stem cell growth, differentiation and morphology, as well as the production of biomimetic scaffolds that respond to programmed signals. Advances in deciphering the mechanisms of action of these important molecules will lead to the implementation and success of their vital applications.

Hsp90 in Cancer: Beyond the Usual Suspects, the latest volume in the Advances in Cancer Research series, focuses on the multifunctional molecular chaperone Hsp90 which regulates the post-translational stability and function of a broad repertoire of client proteins and discusses some of the lesser-known aspects of how Hsp90 and its related family members enable oncogenic transformation and malignant progression.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

This book is a passionate account of the scientific breakthroughs that led to the solution of the first protein structures and to the understanding of their function at atomic resolution. The book is divided into self-standing chapters that each deal with a protein or protein family. The subject is presented in a fluid, non-technical style that will engage student and scientists in biochemistry, biophysics, molecular and structure biology and physiology.

This volume introduces bioinformatics research methods for proteins, with special focus on protein post-translational modifications (PTMs) and networks. This book is organized into four parts and covers the basic framework and major resources for analysis of protein sequence, structure, and function; approaches and resources for analysis of protein PTMs, protein-protein interactions (PPIs) and protein networks, including tools for PPI prediction and approaches for the construction of PPI and PTM networks; and bioinformatics approaches in proteomics, including computational methods for mass spectrometry-based proteomics and integrative analysis for alternative splice isoforms, for functional discovery. 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 or computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Protein Bioinformatics: From Protein Modifications and Networks to Proteomics is a valuable resource for readers who wish to learn about state-of-the-art bioinformatics databases and tools, novel computational methods, and future trends in protein and proteomic data analysis in systems biology. This book is useful to researchers who work in the biotechnology and pharmaceutical industries, and in various academic departments, such as biological and medical sciences and computer sciences and engineering.

This detailed volume explores the continuing techniques of studying RNA-protein complexes and interactions as research in these areas expand. After an introductory chapter, the book continues with ways to purify RNA-protein complexes assembled in cells or in isolated cellular extracts, methods for measuring various biochemical activities of RNA-interacting proteins or ribonucleoproteins, biochemical methods for measuring direct RNA-protein contact, as well as various new or innovative methods pertinent to the subject. Written for the highly successful Methods in Molecular Biology series, chapters contain brief 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, RNA-Protein Complexes and Interactions: Methods and Protocols provides a set of useful protocols, both basic and advanced, designed to inspire researchers working with RNA and RNA-interacting proteins.

This is the second volume in a series on membrane protein transfer. Membrane protein transport underlies the topological disposition of many proteins within cells and it is this disposition that allows for the co-ordination of the central cellular processes, such as metabolism.

This second edition volume expands on the previous edition with an update on the latest developments in the field and new techniques used to study secondary and supersecondary structures (SSS) in proteins. Chapters in this book discuss topics such as sequence and structural features of different SSS elements; software used for the automatic annotation of secondary structure elements in proteins; the new developments in secondary and SSS prediction and the modern approaches for energy landscape calculation; protein misfolding and amyloid structural formation; analysis of 'transformer proteins'; discovery of the structure of the hydrophobic nucleus; and discussions of the main principles of protein structures formation. The contributing authors of the volume are the eminent experts in the field of protein research and bioinformatics. 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 authoritative, Protein Supersecondary Structures: Methods and Protocols, Second Edition is a valuable resource for researchers who are interested in learning more about the relationship between amino acids sequences and protein structures, the evolution of proteins and the dynamics of protein formation.

This volume provides up-to-date scientific achievements from the world's top researchers. Recombinant Proteins from Plants: Methods and Protocols, Second Edition guides readers through protocolsfor use with a variety of plant expression systems. Various aspects of production are covered including vector selection and cloning; product improvements for stability, glycosylation, and antibiotic-free selection; extraction and scale-up; and analysis of transgenic plants and their recombinant proteins. Written for the 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, Recombinant Proteins from Plants: Methods and Protocols, Second Edition is an ideal reference for those who are interested in plant molecular biology and molecular farming.

This volume covers past and present western blot techniques, such as diffusion blotting, slice blotting, blotting of high and low molecular weight proteins, single cell blotting and automated blotting. 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 cutting-edge, Western Blotting: Methods and Protocols will serve as an invaluable reference for those interested in further study into this fascinating field.

This book will address the growing roles of epigenetics in disease pathogenesis, and review the contribution of epigenetic modifications to disease onset and progression. The roles that epigenetics plays in facilitating effects of the environment on allergy and immunologic diseases will be reviewed. The book is divided into three parts - the first is an introduction to epigenetics and the methods that have been developed to study epigenetics, the second addresses epigenetics in allergic diseases and the third part will cover epigenetics in autoimmune diseases. With the rapid expansion of knowledge of how genes are regulated and how this regulation affects disease phenotypes, this book will be attractive to experienced researchers as well as those just launching an epigenetics research program. It will also be of interest to allergist, immunologists, rheumatologists and dermatologist who are engaged in clinical practice as a resource for understanding the basis for personalized and precision medicine. For example, the role that epigenetics plays in the pathogenesis in various allergic and autoimmune disorders and how this determines disease phenotypes will be covered extensively in this book. This book will thus help fill the gap in available resources on epigenetics in allergy and autoimmune diseases.

This volume provides an up-to-date, in-depth overview of the methods that have been applied to studying the complex metalloproteins at a molecular level. Chapters cover a wide range of approaches focusing on genetic, biochemical, spectroscopic, chemical methods, and theoretical calculations. 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, Metalloproteins: Methods and Protocols aims to be useful for anyone who is interested in metalloprotein research and wants to address the unanswered mechanistic and biosynthetic questions of these fascinating enzyme systems.

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.

"Galectins: Methods and Protocols "is the first book solely dedicated to methodological approaches designed to study galectin function. The galectin family represents one of the most pleiotropic families, with individual members having been implicated in various aspects of nearly every biological process described, from RNA splicing to complex regulatory circuits that orchestrate adaptive immunity. Given the diverse roles of galectins in a variety of biological systems, studying these glycan binding proteins often requires the assimilation of diverse technical skills to fully appreciate their biological function. Their nearly ubiquitous expression and ability to bind highly modifiable carbohydrate ligands, in addition to a variety of other regulatory proteins, allows these glycan binding proteins (GBPs) to possess the capacity to regulate a wide variety of biological processes. Individual chapters are dedicated to examining salient features of galectin functions. 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, "Galectins: Methods and Protocols "seeks to serve both professionals and novices with a useful framework when examining galectin function for many years to come."

Over the last decades, amino acids have been found to be of importance in many fields of science. Apart from their biological function, this family of organic compounds has been employed in the synthesis of a vast variety of salts, with impact on areas such as materials science, pharmaceutical or physical research. This covers a wide range, from the discovery of important ferroelectrics or non-linear optical materials to nutrients, flavor enhancers or drugs. This book describes amino acids and their salts with cations, anions and inorganic compounds from a chemical, physical and crystallographical point of view. Additional data on structural properties, crystal growth and the relation of structure and physical properties of amino acid salts is discussed.

This volume explores numerous techniques for the genetic, molecular, biochemical, and structural examination of BCL-2 family proteins and their interactions. The chapters in this book cover topics such as the relevance of BCL-2 proteins in health and disease; evaluating cellular dependencies to specific BCL-2 family proteins; flow-cytometry-based methods for measuring BCL-2 proteins and mitochondrial-based cell death; measuring activity and interactions of BCL-2 family proteins in the presence of mitochondria, artificial membranes or yeast; conformational activation and oligomerization of pro-apoptotic proteins BAX and BAK leading to cytochrome c release and apoptosis; structural and biophysical studies in solution and lipid vesicles using nuclear magnetic resonance, cryo-electron microscopy, fluorescence microscopy and electron paramagnetic resonance. 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, BCL-2 Family Proteins: Methods and Protocols is a valuable resource to inspire and encourage novice and established scientists to further their research and make new discoveries in this exciting field.

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.

This volume compiles methodologies used for detailed studies of histone variants, from their basic properties to their functional roles in chromatin and as vectors of epigenetic information. Its four sections cover experimental approaches to probe the biochemistry of histone variants and variant nucleosomes; their dynamics throughout the cell cycle and at specific genomic locations; their functional impact on chromosome organization and genome stability; and their importance in development, disease and evolution. Written in the highly successful Methods in Molecular Biology series format, chapters include lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, illustrations on the expected results, and tips on troubleshooting and avoiding known pitfalls. This anthology brings together contributions from many of the most highly recognized investigators in this community. Cutting-edge and thorough, Histone Variants: Methods and Protocols is a valuable resource for anyone interested in exploring the experimental and collaborative possibilities in this evolving field.

The book focuses on the current research of the relation between protein phosphorylation and meat quality, reviews the influence mechanism of protein phosphorylation on meat quality, and summarizes the improvement of meat quality by regulating protein phosphorylation. It could help to clarify some dilemmas and encourage further research in this field, aiming for effective application of protein phosphorylation in meat quality in the near future. The book is written for researchers and graduate students in the field of meat science, food chemistry and molecular biology etc.

This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This is the first of two volumes covering protein kinase inhibitors in research and medicine, and includes chapters on such topics as fragment-based screening, broad kinome profiling of kinase inhibitors, and designing drug-resistant kinase alleles.
First of two volumes focusing on protein kinase inhibitors in research and medicinePart of the Methods in Enzymology serial with authors who are experts in their disciplines