Gabriel Waksman Institute of Structural Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, United Kingdom Address for correspondence: Professor Gabriel Waksman Institute of Structural Molecular Biology Birkbeck and University College London Malet Street London WC1E 7H United Kingdom Email: g. waksman@bbk. ac. uk and g. waksman@ucl. ac. uk Phone: (+44) (0) 207 631 6833 Fax: (+44) (0) 207 631 6833 URL: http://people. cryst. bbk. ac. uk/?ubcg54a Gabriel Waksman is Professor of Structural Molecular Biology at the Institute of Structural Molecular Biology at UCL/Birkbeck, of which he is also the director. Before joining the faculty of UCL and Birkbeck, he was the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics at the Washington University School of Medicine in St Louis (USA). The rapidly evolving ?eld of protein science has now come to realize the ubiquity and importance of protein–protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of hi- throughput proteomics to monitor protein–protein interactions at an organism level, we can now safely state that protein–protein interactions are the norm and not the exception.
The rapidly evolving field of protein science has now come to realize the ubiquity and importance of protein-protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of high throughput proteomics to monitor protein-protein interactions at an organism level, we can now safely state that protein-protein interactions are the norm and not the exception. Thus, protein function must be understood in the larger context of the various binding complexes that each protein may form with interacting partners at a given time in the life cycle of a cell. Proteins are now seen as forming sophisticated interaction networks subject to remarkable regulation. The study of these interaction networks and regulatory mechanism, which I would like to term "systems proteomics," is one of the thriving fields of proteomics. The bird-eye view that systems proteomics offers should not however mask the fact that proteins are each characterized by a unique set of physical and chemical properties. In other words, no protein looks and behaves like another. This complicates enormously the design of high-throughput proteomics methods. Unlike genes, which, by and large, display similar physico-chemical behaviors and thus can be easily used in a high throughput mode, proteins are not easily amenable to the same treatment. It is thus important to remind researchers active in the proteomics field the fundamental basis of protein chemistry. This book attempts to bridge the two extreme ends of protein science: on one end, systems proteomics, which describes, at a system level, the intricate connection network that proteins form in a cell, and on the other end, protein chemistry and biophysics, which describe the molecular properties of individual proteins and the structural and thermodynamic basis of their interactions within the network. Bridging the two ends of the spectrum is bioinformatics and computational chemistry. Large data sets created by systems proteomics need to be mined for meaningful information, methods need to be designed and implemented to improve experimental designs, extract signal over noise, and reject artifacts, and predictive methods need to be worked out and put to the test. Computational chemistry faces similar challenges. The prediction of binding thermodynamics of protein-protein interaction is still in its infancy. Proteins are large objects, and simplifying assumptions and shortcuts still need to be applied to make simulations manageable, and this despite exponential progress in computer technology. Finally, the study of proteins impacts directly on human health. It is an obvious statement to say that, for decades, enzymes, receptors, and key regulator proteins have been targeted for drug discovery. However, a recent and exciting development is the exploitation of our knowledge of protein-protein interaction for the design of new pharmaceuticals. This presents particular challenges because protein-protein interfaces are generally shallow and interactions are weak. However, progress is clearly being made and the book seeks to provide examples of successes in this area.
This detailed volume provides a comprehensive collection of classic and cutting-edge methods and techniques in mapping protein-protein interactions. The chapters include a variety of in vitro and in vivo experimental methods covering cell biology, biochemistry, and biophysics. In addition, the book also explores in silico methods including sequence-, structure-, and phylogenetic profile-based approaches as well as gene expression and machine learning methods. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, as well as tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Protein-Protein Interactions: Methods and Protocols serves as an ideal guide for researchers working in protein science and beyond.
Proteomics is an introduction to the exciting new field of proteomics, an interdisciplinary science that includes biology, bioinformatics, and protein chemistry. The purpose of this book is to provide the active researcher with an overview of the types of questions being addressed in proteomics studies and the technologies used to address those questions. Key subjects covered in this book include: an assessment of the limitations of this approach and outlines new developments in mass spectrometry that will advance future research high-throughput recombinant DNA cloning methods used to systematically clone all of the open reading frames of an organism into plasmid vectors for large scale protein expression and functional studies such as protein-protein interactions with the two-hybrid system protein structure an overview of large-scale experimental attempts to determine the three-dimensional structures of representative sets of proteins computational approaches to determining the three-dimensional structure of proteins. Proteomics provides a starting point for researchers who would like a theoretical understanding of the new technologies in the field, and obtain a solid grasp of the fundamentals before integrating new tools into their experiments. Written with attention to detail, but without being overwhelmingly technical, Proteomics is a user-friendly guide needed by most biologists today.
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.
This volume explores techniques that study interactions between proteins in different species, and combines them with context-specific data, analysis of omics datasets, and assembles individual interactions into higher-order semantic units, i.e., protein complexes and functional modules. The chapters in this book cover computational methods that solve diverse tasks such as the prediction of functional protein-protein interactions; the alignment-based comparison of interaction networks by SANA; using the RaptorX-ComplexContact webserver to predict inter-protein residue-residue contacts; the docking of alternative confirmations of proteins participating in binary interactions and the visually-guided selection of a docking model using COZOID; the detection of novel functional units by KeyPathwayMiner and how PathClass can use such de novo pathways to classify breast cancer subtypes. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary hardware- and software, step-by-step, readily reproducible computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Protein-Protein Interaction Networks: Methods and Protocols is a valuable resource for both novice and expert researchers who are interested in learning more about this evolving field.
The chapters in this book are written by a team of well-reputed international researchers. The objective is to provide advanced and updated information related to protein-protein interactions. I hope the methods, resources and approaches described here will enhance the available knowledge of the reader significantly.
Protein-Protein Interactions in Human Disease, Part A, Volume 110 aims to promote further research and development in the protein interaction network as a means to not only identify the critical proteins involved in the etiology of human diseases, but also identify new protein targets for drug development. Sections cover such topics as protein-protein interaction modulators for epigenetic therapies, intrinsic disorder, protein-protein interactions and disease, targeting protein-protein interactions in the ubiquitin-proteasome pathway, the proteomics of occupational diseases, and computational methods in predicting the impact of SNPs in protein-protein network, amongst other topics. Describes advances in the application of powerful techniques in studying and analyzing protein-protein interactions Targeted to a wide audience of researchers, specialists and students Written by authorities in their field Includes information that is well supported by a number of high quality illustrations, figures and tables
Following the succesful publication of "Proteome and Protein Analysis" in 2000, which was based on a former MPSA (Methods in Protein Structure Analysis) conference, Methods in Proteome and Protein Analysis presents the most interesting papers from the 14th MPSA meeting. Major topics include: protein and peptide sample preparation and separation; new reagent for protein sequence analysis; mass spectrometry in protein research; analysis of posttranslational modification; protein-protein interaction using MALDI-MS; manipulation of genome or functional compositon trap; structure-function correlation study using optical biosensors of microcolorimetrical techniques; structural proteomics as NMR or fluorescence polarization study; the classification and prediction of structure or functional sites; in silico analysis of proteins and proteomes; increasing throughput and data quality for proteomics.
