The analysis of protein-protein interactions is fundamental to the understanding of cellular organization, processes, and functions. Proteins seldom act as single isolated species; rather, proteins involved in the same cellular processes often interact with each other. Functions of uncharacterized proteins can be predicted through comparison with the interactions of similar known proteins. Recent large-scale investigations of protein-protein interactions using such techniques as two-hybrid systems, mass spectrometry, and protein microarrays have enriched the available protein interaction data and facilitated the construction of integrated protein-protein interaction networks. The resulting large volume of protein-protein interaction data has posed a challenge to experimental investigation. This book provides a comprehensive understanding of the computational methods available for the analysis of protein-protein interaction networks. It offers an in-depth survey of a range of approaches, including statistical, topological, data-mining, and ontology-based methods. The author discusses the fundamental principles underlying each of these approaches and their respective benefits and drawbacks, and she offers suggestions for future research.

Concanavalin A (Con A), a plant lectin, has become an object of extensive research not only for the biochemist, but also for the bi ologist, biophysicist, pathologist, immunologist and others. On April 19-20, 1974 a group of scholars from four continents met on the campus of the University of Oklahoma for an International Symposium on Con A. This volume contains all lectures presented by the invited speakers on this occasion, as well as the abstracts for all shorter technical papers which were presented. Further, the edi tors invited additional contributions from a few selected laboratories to cover the areas not covered in the symposium itself. This volume then reports the present status of research with Con A. In a sense it is encyclopedic and should be a useful reference tool to the worker in this field. The newcomer to this area will find that a careful study of this book will bring him up-to-date with the latest techniques, ap proaches and the "state of the art" in this specialized area of re search, as well as with traps and ensnarements in which he need not get entangled again. Starting at the molecular level and advancing from there to the organismic level as well as to a number of highly specialized areas, this volume presents the most complete survey of research findings with Con A available today. The editors wish to acknowledge the generous financial support provided by the University of Oklahoma through its President, Dr."

The present volume contains the proceedings of the 23rd Mos bach Colloquium on "Protein-Protein Interactions." It includes the paper by Prof. S. LIFSON who unfortunately was unable to attend. Discussions were included whenever possible in order to make the complete proceedings accessible to the future reader. The colloquium was generously supported by the firms who are corporate members of the Gesellschaft fur Biologische Chemie. Dr. W. B. GRATZER and Dr. L. JAENICKE, as weIl as some of the invited speakers, were a tremendous help in preparing the program and we wish to thank them for their helpfuI suggestions and advice. Our appreciation extends to Prof. E. AUHAGEN and Prof. H. GIBIAN, and their secretaries, who shared the burden of organizing the colloquium. In addition, we wish to express our gratitude to Springer-Ver Iag, and especially to Dr. H. MAYER-KAUPP for editoriaI help and for the rapid publication of this volume. We hope that the reader, Iike the audience in the Mosbach market hall, will gain an impression of the present state of protein research and of the way in which intermolecular interactions hold specific implications for the structure and function of proteins. Regensburg and Wurzburg, autumn 1972 R. JAENICKE E. HELMREICH Contents Introduction. R. JAENICKE (Regensburg) 1 Molecular Forees. S. LIFSON (Rehovot) ................... 3 Structure, Function and Dynamics of a ReguIatory Enzyme: Aspartate Transcarbamylase. H. K. SCHACHMAN (Berkeley) 17 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 . . . . . . . . . . . . . ."

Knowledge of cholesterol and its interaction with protein molecules is of fundamental importance in both animal and human biology. This book contains 22 chapters, dealing in depth with structural and functional aspects of the currently known and extremely diverse unrelated families of cholesterol-binding and cholesterol transport proteins. By drawing together this range of topics the Editor has attempted to correlate this broad field of study for the first time. Technical aspects are given considerable emphasis, particularly in relation cholesterol reporter molecules and to the isolation and study of membrane cholesterol- and sphingomyelin-rich "raft" domains. Cell biological, biochemical and clinical topics are included in this book, which serve to emphasize the acknowledged and important benefits to be gained from the study of cholesterol and cholesterol-binding proteins within the biomedical sciences and the involvement of cholesterol in several clinical disorders. It is hoped that by presenting this topic in this integrated manner that an appreciation of the fact that there is much more that needs to be taken into account, studied and understood than the widely discussed "bad and good cholesterol" associated, respectively, with the low- and high-density lipoproteins, LDL and HDL.

The Proceedings of the Fourth International Metallothionein Meeting (MT-97) feature the latest research on metallothionein. The book covers a broad range of topics which provide important information for both basic and clinical investigators. The selected 94 articles in this book are written by the leading scientists in the field around the world. This is an increasingly important, multi-disciplinary area of study that has benefitted from recent advances in concepts and methodologies from other fields.

The feld of proteomics moves rapidly. New methods, techniques, applications, standards, models and software appear almost on a daily basis. Accompanying this are plenty of texts on the experimental side of the feld and a few appearing on the informatic and data analysis side. This latterly includes one in the Methods in Molecular Biology series tackling the specifc analysis of "Mass spectrometry data in proteomics" in MMB vol. 376. This current collection builds on this, but takes a broader view of proteome data analysis covering data analysis essentials, but also the databases and data models, as well as practical consid- ations for analysing database search results, annotating genomes, and speeding up searches. It also digs deeper into some topics, such as decoy database searching and aspects of signal processing in proteomic mass spectrometry. The aim of the volume is to provide the reader with a mix of reviews and methodology chapters, which build from the essentials of database searching in proteomics, on through specifc data processing challenges to databases, data standards and data models.

From the basic science to potential and approved clinical applications the most recent data in the rapidly growing field of bone morphogenetic proteins (BMPs) are summarized in this topical volume. Distinguished scientists present reviews on a range of scientific topics, including biochemistry, biology, molecular biology and preclinical animal studies on spinal fusion, cartilage repair, craniofacial and dental reconstruction using BMPs, as well as approved clinical applications in human bone non-unions.

This book provides a resource not only for experts in the field, but also for undergraduate students, newcomers and clinicians worldwide, given that the use of BMPs in orthopedic reconstruction has been already approved in Europe, Australia, Canada and the USA.

A number of apparently unrelated phenomena in biological systems (e.g., biopolymer aggregation, cell-cell interactions, ion transport across membranes) arise from the special properties of charged surfaces. A sym posium entitled "Electrical Double Layers in Biology," which took place at the Toronto meeting of the Electrochemical Society, 12-17 May 1985, focused on the common features of these phenomena. The papers presented at that symposium are collected here and they illustrate ways in which an under standing of electrical double layers can elucidate a problem in Biology. An example of this approach can be seen from the paper I presented on ion transport and excitation, where the "unusual" ion flows during nerve excitation are actually expected if one includes the effects of electrical double layers at membrane surfaces. Furthermore, the selectivity of the ion channels in these membranes can be better understood on this basis. Other presentations account for such observations as the changes in spacing between muscle proteins during contraction, the interactions of red cells to form rouleaux, the electrical properties of algal cell membranes, electrokinetic potentials during blood flow in arteries, etc. I trust that these papers will indicate the value of electrochemistry in the study of biological systems, an area of research usually called Bioelectrochemistry, and will encourage biologists to use these ideas when approaching related problems."

This volume contains the proceedings of the International Conference on Prostaglandins and Lipid Metabolism in Radiation Injury held in Rockville, Maryland, on October 2-3, 1986. Over 200 persons from eight countries attended the program, which consisted of 24 oral presentations and 38 poster presentations. Forty-two of those presentations have been included in this volume. The conference was sponsored by the Armed Forces Radiobiology Research Institute, located in Bethesda, Maryland. The effects of radiation on lipid synthesis and membrane damage are aptly summarized in the first five chapters. These chapters describe the effects of radiation on lipid peroxidation of model membranes, and the role of lipid composition in mammalian cell death and in bacterial radio- and thermosensitivity. In bacteria, lipid peroxidation is not essential for radiation-induced cell death. One of the key points of the conference was the paradoxical nature of the radiobiology of eicosanoids. On the one hand, eicosanoids are mediators of damage; on the other, they are radioprotective agents. It is clear from the literature and from the data presented at the conference that both of these properties may also be observed as a consequence of radiotherapy. Some studies indicate that nonsteroidal anti-inflammatory drugs may minimize or prevent certain radiation induced damage, but other studies show no positive effect."

The book addresses the most recent developments in structural and functional proteomics underlying the recent contributions given in these areas by our laboratory to the instrumentations, the methods and the procedures as mutuated from the nanoscale sciences and technologies. These developments introduced in the last few years make now possible protein massive identification (mass spectrometry and biomolecular arrays down to nanoamounts) and protein structural characterization in solution and in crystals down to the atomic scale to an extent and to a degree so far unmatched. Emphasis is placed in the growth by nanobiofilm template of protein crystals of any type and size from millimeter to micron, leading in combination with microfocus synchrotron technology and atomic force microscopy to the definition of a new field called nanocrystallography. The few useful examples being shown, concerning yet structurally unsolved proteins, point this very promising approach nanotechnology-based in structural proteomics using highly focused X-rays. This has not to be confused with the important study of nanocrystals, both organic and inorganic, and novel diamond like nanocomposite materials and devices having 3D protein crystals as matrices to be equilibrated with nanoparticles/gold/silver to be utilized in the most diversified electronic applications here also summarized. vii Acknowledgments We are particularly grateful to Giuseppe Zanotti at the University of Padova for his fundamental collaboration during all the crystallographic studies.

Physics and the life sciences have established new connections within the past few decades, resulting in biological physics as an established subfield with strong groups working in many physics departments. These interactions between physics and biology form a two-way street with physics providing new tools and concepts for understanding life, while biological systems can yield new insights into the physics of complex systems. To address the challenges of this interdisciplinary area, The Physics of Proteins: An Introduction to Biological Physics and Molecular Biophysics is divided into three interconnected sections. In Parts I and II, early chapters introduce the terminology and describe the main biological systems that physicists will encounter. Similarities between biomolecules, glasses, and solids are stressed with an emphasis on the fundamental concepts of living systems. The central section (Parts III and IV) delves into the dynamics of complex systems. A main theme is the realization that biological systems, in particular proteins, do not exist in unique conformations but can assume a very large number of slightly different structures. This complexity is captured in the concept of a free energy landscape and leads to the conclusion that fluctuations are crucial for the functioning of biological systems. The final chapter of this section challenges the reader to apply these concepts to a problem that appears in the current literature. An extensive series of appendices (Part V) provide descriptions of the key physical tools and analytical methods that have proven powerful in the study of the physics of proteins. The appendices are designed to be consulted throughout the section on protein dynamics without breaking the deductive flow of the logic in the central section of the book.

The First European Symposium on Calcium-Binding Proteins in Normal and Transformed Cells was held at the Faculty of Medicine of the "Universit6 Libre de Bruxelles" in Brussels, Belgium, April 20-22, 1989. Delegates from seventeen countries attended. This Symposium was initiated through an EEC Stimulation Program. The formal program included forty verbal presentations by invited speakers and sixty miniposter presentations, and was formulated by the Organizing and Scientific Committee: E. Carmeliet (Leuven), J. P. Collin (Poitiers), S. Forsen (Lund), C. W. Heizmann (Ziirich), D. E. M. Lawson (Cambridge), P. Miroir (Brussels), J. L. Pasteels (Brussels) and R. Pochet (Brussels). This volume contains the papers prepared by the invited speakers. The contributions are grouped according to their general subject matter: Genes of Calcium-Binding Protein Family, Structure/Function Relationships, The Cytoskeleton and Calcium-Binding Proteins, Calcium-Binding Proteins in TransforlIled Cells, Calcium/Lipid-Binding Proteins, Calcium-Binding Proteins Substrates and Immunohistochemistry of Calbindin and Calretinin. The highlights of the symposium are numerous. Among the items to be noted are the growing number of abundant proteins which interact with calcium and sometimes with other second messenger sys- tems; specifically pH associated with the tyrosine kinase calpactin, calcYclin, p9Ka induced by growth fac- tors, MRP-8 and MRP-14 (also called cystic fibrosis antigen, L1 or calgranulins) forming half the soluble protein of granulocytes. New structure/function relationships on calbindin D9K and calmodulin have emerged from nuclear magnetic resonance and site-directed mutagenesis studies.

In the early 1980s, a few scientists started working on a Xenopus transcription factor, TFIIIA. They soon discovered a novel domain associated with zinc, and named this domain "zinc finger. " Th e number of proteins with similar zinc fingers grew quickly and these proteins are now called C2H2, Cys2His2 or classical zinc finger proteins. To date, about 24,000 C2H2 zinc finger proteins have been recognized. Approximately 700 human genes, or more than 2% of the genome, have been estimated to encode C2H2 finger proteins. From the beginning these proteins were thought to be numerous, but no one could have predicted such a huge number. Perhaps thousands of scientists are now working on C2H2 zinc finger proteins fi-om variou s viewpoints. This field is a good example of how a new science begins with the insight of a few scientists and how it develops by efforts of numerous independent scientists, in contrast to a policy-driven scientific project, such as the Human Genome Project, with goals clearly set at its inception and with work performed by a huge collaboration throughout the world. As more zinc finger proteins were discovered, several subfamilies, such as C2C2, CCHC, CCCH, LIM, RING, TAZ, and FYVE emerged, increasing our understanding of zinc fingers. The knowledge was overwhelming. Moreover, scientists began defining the term "zinc finger" differently and using various names for identical zinc fingers. These complications may explain why no single comprehensive resource of zinc finger proteins was available before this publication.

The objective of this volume is to provide readers with a current view of all aspects of the 'pipeline' that takes protein targets to structures and how these have been optimised. This volume includes chapters describing, in-depth, the individual steps in the Structural Genomics pipeline, as well as less detailed overviews of individual Structural Genomics initiatives. It is the first book of protocols to cover techniques in a new and emerging field.

In recent years remarkable progress has been accomplished with respect to our knowledge about bacterial protein toxins. This refers especially to structural aspects of protein toxins but also holds true for genetics, molecular biology and biochemical mechanisms underlying the action of toxins. This volume covers the very current and exciting aspects of up-to-date bacterial toxicology and comprehensively reviews the most important bacterial protein toxins such as the intracellular acting toxins which exhibit enzyme activity, as well as those toxins that interact with cell plasma membranes by damaging the membranes (pore formation) or stimulating cell receptors (superantigens). This is the most current reference work on these important bacterial protein toxins, which are presented from the point of view of different disciplines such as pharmacology, microbiology, cell biology and protein chemistry.

Quantitative Proteomics by Mass Spectrometry, from the Methods in Molecular Biology series, is a compendium of cutting-edge protocols for quantitative proteomics, and presents the most significant methods used in the field today. The focus on mass spectrometry (MS) is integral, as MS has, and will continue to be, an essential tool in proteomics for studying complex biological systems and human diseases. This volume, written and compiled by leading quantitative proteomic experts, is an indispensable resource in the search for novel biomarkers.
Quantitative Proteomics by Mass Spectrometry presents several innovative MS quantitative procedures, including a variety of methods for introducing isotopic labels and quantifying post-translational modifications. Some of these methods include growing an organism in isotope-enriched media, performing trypsin proteolysis in the presence of 18O-water, reacting protein samples with isotopically labeled reagents, quantifying relative amount of proteins without the use of any isotopic labels. Attention is also given to state-of-the-art techniques for the characterization of the phosphoproteome and tandem MS for detection of inborn errors of metabolism. Specifically, the procedure for determinations of enzymatic activity could be used for large-scale screening of newborns. The protocols in this volume expand both the breadth and depth of readily available methods for quantitative proteomic researchers using MS.

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This book presents broad coverage of the principles and recent developments of sample preparation and fractionation tools in Expression Proteomics in general and two-dimensional electrophoresis (2-DE) in particular. With its unique capacity to resolve thousands of proteins in a single run, 2-DE is still a fundamental research tool for nearly all protein-related scientific projects.

Volume One of this two-volume sequence focuses on the basic characterization of known protein structures, and structure prediction from protein sequence information. Eleven chapters survey of the field, covering key topics in modeling, force fields, classification, computational methods, and structure prediction. Each chapter is a self contained review covering definition of the problem and historical perspective; mathematical formulation; computational methods and algorithms; performance results; existing software; strengths, pitfalls, challenges, and future research.

One ofthe major drivers in biological research is the establishment ofstructures and functions of the 50,000 or so proteins in our bodies. Each has a characteristic- dimensional structure, highly "ordered" yet "disordered"! This structure is essential for a protein's function and, significantly, it must be sustained in the competitive and complex environment of the living cell. It is now being recognised that when a cell loses control, proteins can se- assemble into more complex supermolecular structures such as the amyloid fibres and plaques associated with the pathogenesis of prion (CJD) or age-related (Alzheimer's) diseases. This is a pointer to the wider significance of the self-assembling properties of polypeptides. It has been long known that, in silk, polypeptides are assembled into- sheet structures which impart on the material its highly exploitable properties of flexibility combined with high tensile strength. But only now emerging is the recognition that peptides can Self-assemble into a wide variety of non-protein-like structures, including fibrils, fibres, tubules, sheets and monolayers. These are exciting observations and, more so, the potential for materials and medical exploitations is so wide ranging that over 80 scientists from Europe, USA, Japan and Israel. met 1-6 July 1999 in Crete, to discuss the wide-ranging implications of these novel developments. There was a spirit of excitement about the workshop indicative of an important new endeavor. The emerging perception is that of a new class of materials set to become commercially viable early in the 21st century.

Amino acids are featured in course syllabuses and in project and research work over a wide spectrum of subject areas in chemistry and biology. Chemists and biochemists using amino acids have many common needs when they turn to the literature for comprehensive information. Among these common interests, analytical studies, in particular, have undergone rapid development in recent years. All other chemical and biochemical aspects of amino acids - synthesis, properties and reactions, preparation of derivatives for use in peptide synthesis, racemization and other fundamental mechanistic knowledge - have been the subject of vigorous progress. This book offers a thorough treatment of all these developing areas, and is structured in the belief that biochemists, physiologists and others will profit from access to information on topics such as the physical chemistry of amino acid solutions, as well as from thorough coverage of amino acid metabolism, biosynthesis and enzyme inhibition; and that chemists will find relevant material in biological areas as well as in the analysis, synthesis and reactions of amino acids.

In the areas of biochemistry and cell biology, characterizations of stability and molecular interactions call for a quantitative approach with a level of precision that matches the fine tuning of these interactions in a living cell. Supporting and up-dating previous Methods in Molecular Biology (TM) volumes, Protein Structure, Stability, and Interactions approaches its subject with a focus on theory and practical applications for both established methods as well as exciting new procedures. The volume presents an overview of many techniques currently used to study protein stability and interactions, including scanning and titration calorimetry, spectroscopic methods, high field NMR, and analytical ultracentrifugation. As a volume of the highly successful Methods in Molecular Biology (TM) series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Cutting-edge and easy to reference, Protein Structure, Stability, and Interactions is an ideal guide for all scientists interested in biomolecular interactions.

Intended for Molecular Biologists, Biochemists, and Geneticists interested in manipulating and analyzing the Hedgehog Signaling Pathway, this volume offers various detailed chapters on experimental description, including anecdotal pointers and notes.

Protein phosphorylation controls many basic cellular processes, such as cell growth, differentiation, migration, metabolism, and cell death, and its study can provide key insights into the signal transduction pathways that are activated in cells in response to different stimuli, such as growth factor stimulation or exposure to toxicants. In Phospho-Proteomics: Methods and Protocols, expert researchers contribute both well-established protocols and some of the newest strategies for the identification and evaluation of protein phosphorylation on Tyr, Ser, and Thr residues, including topics such as 2-dimensional gel electrophoresis and protein phosphorylation, enrichment of phospho-proteins and peptides, quantitative analysis of phosphorylation by labeling and MS analysis, and antibody and kinase arrays. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Phospho-Proteomics: Methods and Protocols is an ideal reference for both new and experienced scientists who wish to gain insight into the current developments in the field and to find inspiration to pursue its future.

In this book, a select group of researchers has contributed their state-of-the-art methodologies on protein profiling and identification of disease biomarkers in tissues, microdissected cells and body fluids. The book integrates biochemistry, pathology, analytical technology, bioinformatics, and proteome informatics. Experimental approaches are thoroughly detailed and explained through a step-by-step instructional format that ensures successful results.