Protein Allostery in Drug Discovery


Book Description

The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery—as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc.




Allosterism in Drug Discovery


Book Description

Although the concept of allosterism has been known for over half a century, its application in drug discovery has exploded in recent years. The emergence of novel technologies that enable molecular-level ligand-receptor interactions to be studied in studied in unprecedented detail has driven this trend. This book, written by the leaders in this young research area, describes the latest developments in allosterism for drug discovery. Bringing together research in a diverse range of scientific disciplines, Allosterism in Drug Discovery is a key reference for academics and industrialists interested in understanding allosteric interactions. The book provides an in-depth review of research using small molecules as chemical probes and drug candidates that interact allosterically with proteins of relevance to life sciences and human disease. Knowledge of these interactions can then be applied in the discovery of the novel therapeutics of the future. This book will be useful for people working in all disciplines associated with drug discovery in academia or industry, as well as postgraduate students who may be working in the design of allosteric modulators.




Structural Biology in Drug Discovery


Book Description

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




Fuzziness


Book Description

Detailed characterization of fuzzy interactions will be of central importance for understanding the diverse biological functions of intrinsically disordered proteins in complex eukaryotic signaling networks. In this volume, Peter Tompa and Monika Fuxreiter have assembled a series of papers that address the issue of fuzziness in molecular interactions. These papers provide a broad overview of the phenomenon of fuzziness and provide compelling examples of the central role played by fuzzy interactions in regulation of cellular signaling processes and in viral infectivity. These contributions summarize the current state of knowledge in this new field and will undoubtedly stimulate future research that will further advance our understanding of fuzziness and its role in biomolecular interactions.







Biomolecular Simulations in Structure-Based Drug Discovery


Book Description

A guide to applying the power of modern simulation tools to better drug design Biomolecular Simulations in Structure-based Drug Discovery offers an up-to-date and comprehensive review of modern simulation tools and their applications in real-life drug discovery, for better and quicker results in structure-based drug design. The authors describe common tools used in the biomolecular simulation of drugs and their targets and offer an analysis of the accuracy of the predictions. They also show how to integrate modeling with other experimental data. Filled with numerous case studies from different therapeutic fields, the book helps professionals to quickly adopt these new methods for their current projects. Experts from the pharmaceutical industry and academic institutions present real-life examples for important target classes such as GPCRs, ion channels and amyloids as well as for common challenges in structure-based drug discovery. Biomolecular Simulations in Structure-based Drug Discovery is an important resource that: -Contains a review of the current generation of biomolecular simulation tools that have the robustness and speed that allows them to be used as routine tools by non-specialists -Includes information on the novel methods and strategies for the modeling of drug-target interactions within the framework of real-life drug discovery and development -Offers numerous illustrative case studies from a wide-range of therapeutic fields -Presents an application-oriented reference that is ideal for those working in the various fields Written for medicinal chemists, professionals in the pharmaceutical industry, and pharmaceutical chemists, Biomolecular Simulations in Structure-based Drug Discovery is a comprehensive resource to modern simulation tools that complement and have the potential to complement or replace laboratory assays for better results in drug design.




Allosteric Modulation of G Protein-Coupled Receptors


Book Description

Allosteric Modulation of G Protein-Coupled Receptors reviews fundamental information on G protein-coupled receptors (GPCRs) and allosteric modulation, presenting original research in the area and collectively providing a comprehensive description of key issues in GPCR allosteric modulation. The book provides background on core concepts of molecular pharmacology while also introducing the most important advances and studies in the area. It also discusses key methodologies. This is an essential book for researchers and advanced students engaged in pharmacology, toxicology and pharmaceutical sciences training and research. Many of the GPCR-targeted drugs released in the past decade have specifically worked via allosteric mechanisms. Unlike direct orthosteric-acting compounds that occupy a similar receptor site to that of endogenous ligands, allosteric modulators alter GPCR-dependent signaling at a site apart from the endogenous ligand. Recent methodological and analytical advances have greatly improved our ability to understand the signaling mechanisms of GPCRs. We now know that allostery is a common regulatory mechanism for all GPCRs and not – as we once believed – unique to a few receptor subfamilies. - Introduces background on core concepts of molecular pharmacology, including statistical analyses, non-linear regression, complex models and GPCR-dependent signal transduction as they relate to allosteric modulation - Discusses critical advances and landmark studies, including discoveries in the area of GPCR allosteric modulation, which are reviewed for their importance in positive and negative regulation, protein-protein interactions, and small molecule drug discovery - Includes key methodologies used to study allosteric modulation at the in silico, in vitro, and in vivo levels of drug discovery and characterization




Protein Actions: Principles and Modeling


Book Description

Protein Actions: Principles and Modeling is aimed at graduates, advanced undergraduates, and any professional who seeks an introduction to the biological, chemical, and physical properties of proteins. Broadly accessible to biophysicists and biochemists, it will be particularly useful to student and professional structural biologists and molecular biophysicists, bioinformaticians and computational biologists, biological chemists (particularly drug designers) and molecular bioengineers. The book begins by introducing the basic principles of protein structure and function. Some readers will be familiar with aspects of this, but the authors build up a more quantitative approach than their competitors. Emphasizing concepts and theory rather than experimental techniques, the book shows how proteins can be analyzed using the disciplines of elementary statistical mechanics, energetics, and kinetics. These chapters illuminate how proteins attain biologically active states and the properties of those states. The book ends with a synopsis the roles of computational biology and bioinformatics in protein science.




Applied Biophysics for Drug Discovery


Book Description

Applied Biophysics for Drug Discovery is a guide to new techniques and approaches to identifying and characterizing small molecules in early drug discovery. Biophysical methods are reasserting their utility in drug discovery and through a combination of the rise of fragment-based drug discovery and an increased focus on more nuanced characterisation of small molecule binding, these methods are playing an increasing role in discovery campaigns. This text emphasizes practical considerations for selecting and deploying core biophysical method, including but not limited to ITC, SPR, and both ligand-detected and protein-detected NMR. Topics covered include: • Design considerations in biophysical-based lead screening • Thermodynamic characterization of protein-compound interactions • Characterizing targets and screening reagents with HDX-MS • Microscale thermophoresis methods (MST) • Screening with Weak Affinity Chromatography • Methods to assess compound residence time • 1D-NMR methods for hit identification • Protein-based NMR methods for SAR development • Industry case studies integrating multiple biophysical methods This text is ideal for academic investigators and industry scientists planning hit characterization campaigns or designing and optimizing screening strategies.




Real World Drug Discovery


Book Description

Drug discovery increasingly requires a common understanding by researchers of the many and diverse factors that go into the making of new medicines. The scientist entering the field will immediately face important issues for which his education may not have prepared him: project teams, patent law, consultants, target product profiles, industry trends, Gantt charts, target validation, pharmacokinetics, proteomics, phenotype assays, biomarkers, and many other unfamiliar topics for which a basic understanding must somehow be obtained. Even the more experienced scientist can find it frustratingly difficult to get an overview of the many factors involved in modern drug discovery and often only after years of exploring does a whole and integrated picture emerge in the mind of the researcher.Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research presents this kind of map of the landscape of drug discovery. In a single, readable volume it outlines processes and explains essential concepts and terms for the recent science graduate wondering what to expect in pharma or biotech, the medicinal chemist seeking a broader and more timely understanding of the industry, or the contractor or collaborator whose understanding of the commercial drug discovery process could increase the value of his contribution to it. - Interviews with well-known experts in many of the fields involved, giving insightful comments from authorities on many of the sub-disciplines important to cutting edge drug discovery. - Helpful suggestions gleaned from years of experience in biotech and pharma, which represents a repository drug discovery "lore" not previously available in any book. - "Periodic Table of Drugs" listing current top-selling drugs arranged by target and laid out so that structural similarities and differences are plain and clear. - Extensive use of diagrams to illustrate concepts like biotech startup models, preteomic profiling for target identification, Gantt charts for project planning, etc.