Protein Families

New insights into the evolution and nature of proteins Exploring several distinct approaches, this book describes the methods for comparing protein sequences and protein structures in order to identify homologous relationships and classify proteins and protein domains into evolutionary families. Readers will discover the common features as well as the key philosophical differences underlying the major protein classification systems, including Pfam, Panther, SCOP, and CATH. Moreover, they'll discover how these systems can be used to understand the evolution of protein families as well as understand and predict the degree to which structural and functional information are shared between relatives in a protein family. Edited and authored by leading international experts, Protein Families offers new insights into protein families that are important to medical research as well as protein families that help us understand biological systems and key biological processes such as cell signaling and the immune response. The book is divided into three sections: Section I: Concepts Underlying Protein Family Classification reviews the major strategies for identifying homologous proteins and classifying them into families. Section II: In-Depth Reviews of Protein Families focuses on some fascinating super protein families for which we have substantial amounts of sequence, structural and functional data, making it possible to trace the emergence of functionally diverse relatives. Section III: Review of Protein Families in Important Biological Systems examines protein families associated with a particular biological theme, such as the cytoskeleton. All chapters are extensively illustrated, including depictions of evolutionary relationships. References at the end of each chapter guide readers to original research papers and reviews in the field. Covering protein family classification systems alongside detailed descriptions of select protein families, this book offers biochemists, molecular biologists, protein scientists, structural biologists, and bioinformaticians new insight into the evolution and nature of proteins.

Volume Two of this two-volume sequence presents a comprehensive overview of protein structure prediction methods and includes protein threading, De novo methods, applications to membrane proteins and protein complexes, structure-based drug design, as well as structure prediction as a systems problem. A series of appendices review the biological and chemical basics related to protein structure, computer science for structural informatics, and prerequisite mathematics and statistics.

A select group of 40 eminent scientists from all parts of the world met to consider the current state of chemical and biological knowledge on the ever-expanding protein universe, and to discuss emerging opportunities for the foreseeable future. Scientific approaches to discover, characterize, and regulate protein functions were discussed over a range of disciplines, including natural product chemistry, microbiology, enzymology, biochemistry, structural biology, chemical biology, and glycobiology. Some notable highlights included discovery of new enzymatic pathways, innovative carbohydrate chemistry, design of proteins containing unnatural amino acids, structural elucidation of complex supramolecular machines, and design and application of small molecule drugs, biologics and biosimilars. This fascinating compendium of scientific presentations and in-depth discussions affords a unique perspective on today's protein chemistry and biology as well as on the challenges for tomorrow. Contents:New Chemistry in the Expanding Protein Universe:Novel Chemistry Still to be Found in Nature (C T Walsh)Natural Product Biosynthesis in the Genomic Age (W A van der Donk)Peptide Dendrimers and Polycyclic Peptides (J-L Reymond)What can Comparative Genomics Reveal about the Mechanisms of Protein Function Evolution? (N L Dawson, R Studer, N Furnham, D Lees, S Das, J Thornton and C Orengo)Exploring Chromatin Biology Using Protein Chemistry (T W Muir)Our Expanding Protein Universe (A Godzik)The Scientific Impact of Freely Available Chemical Probes (A M Edwards)Discussions of Session 1Exploring Enzyme Families and Enzyme Catalysis:Mechanistic Enzymology and Catalyst Design (D Hilvert)Looking in New Directions for the Origins of Enzymatic Rate Accelerations (J P Klinman)Computational Enzyme Design and Methods to Predict the Role of Remote Mutations (K N Houk)Discovering Novel Enzymes, Metabolites and Pathways (J A Gerlt)Programming New Chemistry into the Genetic Code of Cells and Animals (J W Chin)Expanding the Enzyme Universe through a Marriage of Chemistry and Evolution (F H Arnold)Controlled Radical Reactions in Biology and the Importance of Metallo-Cofactor Biosynthesis (J Stubbe)Discussions of Session 2Microbiomes and Carbohydrate Chemistry:Structural Basis for Host/Commensal-Microbe Interactions in the Human Distal Gut Microbiome (I A Wilson)Carbohydrate Chemistry and Biology (C-H Wong)Chemical Biological Proteomics of Bacterial Protein Functionalities in the Human Distal Gut Microbiome (D W Wolan)Automated Oligosaccharide Synthesis: From Insights into Fundamental Glycobiology to Vaccines and Diagnostics (P H Seeberger)Carbohydrate-Active Enzymes in Microbiomes (B Henrissat)The Microbiome(s): Microbiota, Families, Functions (A Godzik)N-Linked Protein Glycosylation (M Aebi)Discussions of Session 3GPCRs and Transporters: Ligands, Cofactors, Drug Development:GPCRs and Transporters: Ligands, Cofactors, Drug Development (G von Heijne)Studies of GPCR Conformations in Non-Crystalline Milieus (K Wüthrich)The Seven Transmembrane Superfamily (R C Stevens)Nanobodies for the Structural and Functional Investigation of GPCR Transmembrane Signaling (E Pardon and J Steyaert)The Hidden Pharmacology of the Human GPCR-ome (B L Roth)Structures and Reaction Mechanisms of ABC Transporters (K Locher)Discussions of Session 4Biologicals and Biosimilars:Biologicals and Biosimilars (S Ghose and M G Grütter)Platform Technologies for the Artificial Pseudo-Natural Product Discovery (H Suga)Anticalins® & Pasylation®: New Concepts for Biopharmaceutical Drug Development from Protein Design (A Skerra)From Natural Antibodies to Synthetic Proteins (S S Sidhu)From Intact Antibodies to Armed Antibodies (D Neri)Regulating Cellular Life Death and Development Using Intracellular Combinatorial Antibody Libraries (R Lerner, J Xie, H Zhang, K Yea, J Blanchard and K Baldwin)Nanobodies: A Universe of Variable Domains and a Toolbox for Many Trades (L Wyns)Discussions of Session 5Proteins in Supramolecular Machines:Assembly of Filamentous Type 1 Pili from Uropathogenic Escherichia Coli Strains (R Glockshuber)HIV Envelope and Influenza Hemagglutinin Fusion Glycoproteins and the Quest for a Universal Vaccine (I A Wilson)Deconstruction of Iterative Polyketide Synthases (C A Townsend)Regulating Ribosome Pausing During Translation (M V Rodnina)The Molecular Mechanics of the Ribosome (J Zhou, L Lancaster, Z Guo, J P Donohue and H F Noller)Exploring the Dynamics of Supramolecular Machines with Cryo-Electron Microscopy (J Frank)Crystallographic Studies of Eukaryotic Ribosomes and Functional Insights (N Ban)Discussions of Session 6 Readership: Graduates and researchers in protein structure, structural biology and genomics. Key Features:Unique approach to the topic, an outstanding group of contributors, extensive inclusion of otherwise unpublished materialKeywords:Proteins;Structural Biology;Structural Genomics;GPCRs;Drug Development

In the years since the publication of Susumu Ohno's 1970 landmark book Evolution by gene duplication tremendous advances have been made in molecular biology and especially in genomics. Studies of genome structure and function prerequisite to testing hypotheses of genome evolution were all but impossible until recent methodological advances. This book evaluates newly generated empirical evidence as it pertains to theories of genomic evolutionary patterns and processes. Tests of hypotheses using analyses of complete genomes, interpreted in a phylogenetic context, provide evidence regarding the relative importance of gene duplication. The alternative explanation is that the evolution of regulatory elements that control the expression of and interactions among genes has been a more important force in shaping evolutionary innovation. This collection of papers will be of interest to all academic and industry researchers working in the fields of molecular biology, biotechnology, genomics and genome centers.

In this volume, a detailed description of cutting-edge computational methods applied to protein modeling as well as specific applications are presented. Chapters include: the application of Car-Parrinello techniques to enzyme mechanisms, the outline and application of QM/MM methods, polarizable force fields, recent methods of ligand docking, molecular dynamics related to NMR spectroscopy, computer optimization of absorption, distribution, metabolism and excretion extended by toxicity for drugs, enzyme design and bioinformatics applied to protein structure prediction. A keen emphasis is laid on the clear presentation of complex concepts, since the book is primarily aimed at Ph.D. students, who need an insight in up-to-date protein modeling. The inclusion of descriptive, color figures will allow the reader to get a pictorial representation of complicated structural issues.

This book describes more than 60 web-accessible computational tools for protein analysis and is totally practical, with detailed explanations on how to use these tools and interpret their results and minimal mentions to their theoretical basis (only when that is required for making a better use of them). It covers a wide range of tools for dealing with different aspects of proteins, from their sequences, to their three-dimensional structures, and the biological networks they are immersed in. The selection of tools is based on the experience of the authors that lead a protein bioinformatics facility in a large research centre, with the additional constraint that the tools should be accessible through standard web browsers without requiring the local installation of specific software, command-line tools, etc. The web tools covered include those aimed to retrieve protein information, look for similar proteins, generate pair-wise and multiple sequence alignments of protein sequences, work with protein domains and motifs, study the phylogeny of a family of proteins, retrieve, manipulate and visualize protein three-dimensional structures, predict protein structural features as well as whole three-dimensional structures, extract biological information from protein structures, summarize large protein sets, study protein interaction and metabolic networks, etc. The book is associated to a dynamic web site that will reflect changes in the web addresses of the tools, updates of these, etc. It also contains QR codes that can be scanned with any device to direct its browser to the tool web site. This monograph will be most valuable for researchers in experimental labs without specific knowledge on bioinformatics or computing.

This book provides a comprehensive overview of the fundamental aspects of protein-protein interactions (PPI), including a detailed account of the energetics and thermodynamics involved in these interactions. It also discusses a number of computational and experimental approaches for the prediction of PPI interactions and reviews their principles, advantages, drawbacks, and the recent developments. Further, it offers structural and mechanistic insights into the formation of protein-protein complexes and maps different PPIs into networks to delineate various pathways that operate at the cellular level. Lastly, it describes computational protein-protein docking techniques and discusses their implications for further experimental research. Given its scope, this book is a valuable resource for students, researchers, scientists, entrepreneurs, and medical/healthcare professionals.