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.

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.

Proteins are indispensable players in virtually all biological events. The functions of proteins are coordinated through intricate regulatory networks of transient protein-protein interactions (PPIs). To predict and/or study PPIs, a wide variety of techniques have been developed over the last several decades. Many in vitro and in vivo assays have been implemented to explore the mechanism of these ubiquitous interactions. However, despite significant advances in these experimental approaches, many limitations exist such as false-positives/false-negatives, difficulty in obtaining crystal structures of proteins, challenges in the detection of transient PPI, among others. To overcome these limitations, many computational approaches have been developed which are becoming increasingly widely used to facilitate the investigation of PPIs. This book has gathered an ensemble of experts in the field, in 22 chapters, which have been broadly categorized into Computational Approaches, Experimental Approaches, and Others.

As the mysteries stored in our DNA have been more completely revealed, scientists have begun to face the extraordinary challenge of unraveling the int- cate network of protein–protein interactions established by that DNA fra- work. It is increasingly clear that proteins continuously interact with one another in a highly regulated fashion to determine cell fate, such as proliferation, diff- entiation, or death. These protein–protein interactions enable and exert str- gent control over DNA replication, RNA transcription, protein translation, macromolecular assembly and degradation, and signal transduction; essentially all cellular functions involve protein–protein interactions. Thus, protein–p- tein interactions are fundamental for normal physiology in all organisms. Alt- ation of critical protein–protein interactions is thought to be involved in the development of many diseases, such as neurodegenerative disorders, cancers, and infectious diseases. Therefore, examination of when and how protein–p- tein interactions occur and how they are controlled is essential for understa- ing diverse biological processes as well as for elucidating the molecular basis of diseases and identifying potential targets for therapeutic interventions. Over the years, many innovative biochemical, biophysical, genetic, and computational approaches have been developed to detect and analyze p- tein–protein interactions. This multitude of techniques is mandated by the diversity of physical and chemical properties of proteins and the sensitivity of protein–protein interactions to cellular conditions.

Protein-protein interactions (PPI) are at the heart of the majority of cellular processes, and are frequently dysregulated or usurped in disease. Given this central role, the inhibition of PPIs has been of significant interest as a means of treating a wide variety of diseases. However, there are inherent challenges in developing molecules capable of disrupting the relatively featureless and large interfacial areas involved. Despite this, there have been a number of successes in this field in recent years using both traditional drug discovery approaches and innovative, interdisciplinary strategies using novel chemical scaffolds. This book comprehensively covers the various aspects of PPI inhibition, encompassing small molecules, peptidomimetics, cyclic peptides, stapled peptides and macrocycles. Illustrated throughout with successful case studies, this book provides a holistic, cutting-edge view of the subject area and is ideal for chemical biologists and medicinal chemists interested in developing PPI inhibitors.

With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins

This volume details protocols that cover the broad arsenal of techniques used to study a secretion system from A to Z. Chapters focus on identifying and localizing the different subunits, defining interactions within subunits, monitoring conformational changes, purifying and imaging of large complexes, defining the assembly pathway by fluorescence microscopy and the role of energy during assembly and/or secretion, identifying secreted effectors as well as reporters to follow effector transport. 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, Bacterial Protein Secretion Systems: Methods and Protocol aims to provide techniques that are not restricted to the study of secretion systems but are also of specific interest for any researcher interested on multi-protein complexes of the bacterial cell envelope.