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This book discusses a broad range of basic and advanced topics in the field of protein structure, function, folding, flexibility, and dynamics. Starting with a basic introduction to protein purification, estimation, storage, and its effect on the protein structure, function, and dynamics, it also discusses various experimental and computational structure determination approaches; the importance of molecular interactions and water in protein stability, folding and dynamics; kinetic and thermodynamic parameters associated with protein-ligand binding; single molecule techniques and their applications in studying protein folding and aggregation; protein quality control; the role of amino acid sequence in protein aggregation; muscarinic acetylcholine receptors, antimuscarinic drugs, and their clinical significances. Further, the book explains the current understanding on the therapeutic importance of the enzyme dopamine beta hydroxylase; structural dynamics and motions in molecular motors; role of cathepsins in controlling degradation of extracellular matrix during disease states; and the important structure-function relationship of iron-binding proteins, ferritins. Overall, the book is an important guide and a comprehensive resource for understanding protein structure, function, dynamics, and interaction.
Proteins lie at the heart of almost all biological processes and have an incredibly wide range of activities. Central to the function of all proteins is their ability to adopt, stably or sometimes transiently, structures that allow for interaction with other molecules. An understanding of the structure of a protein can therefore lead us to a much improved picture of its molecular function. This realisation has been a prime motivation of recent Structural Genomics projects, involving large-scale experimental determination of protein structures, often those of proteins about which little is known of function. These initiatives have, in turn, stimulated the massive development of novel methods for prediction of protein function from structure. Since model structures may also take advantage of new function prediction algorithms, the first part of the book deals with the various ways in which protein structures may be predicted or inferred, including specific treatment of membrane and intrinsically disordered proteins. A detailed consideration of current structure-based function prediction methodologies forms the second part of this book, which concludes with two chapters, focusing specifically on case studies, designed to illustrate the real-world application of these methods. With bang up-to-date texts from world experts, and abundant links to publicly available resources, this book will be invaluable to anyone who studies proteins and the endlessly fascinating relationship between their structure and function.
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.
ATPases Associated with diverse cellular Activities (AAA+) comprise a superfamily of proteins that are defined by the presence of the AAA+ domain containing canonical Walker A and B motifs required for ATP binding and hydrolysis. Members of this superfamily act on other proteins, DNA, RNA, or multicomponent complexes to affect their conformation or their assembly. There have been substantial advances in understanding the structure and mechanism of function of a large number of AAA+ proteins. In this Research Topic, review articles and original research papers discuss new aspects as well as provide a detailed overview of several AAA+ proteins, namely: ClpXP, Lon, ClpB, Hsp104, p97, AAA+ proteins of the proteasome, Rubisco activases, Torsin, Pontin, and Reptin.
This book is a self-contained introduction to the theory of atomic motion in proteins and nucleic acids. An understanding of such motion is essential because it plays a crucially important role in biological activity. The authors, both of whom are well known for their work in this field, describe in detail the major theoretical methods that are likely to be useful in the computer-aided design of drugs, enzymes and other molecules. A variety of theoretical and experimental studies is described and these are critically analyzed to provide a comprehensive picture of dynamic aspects of biomolecular structure and function. The book will be of interest to graduate students and research workers in structural biochemistry (X-ray diffraction and NMR), theoretical chemistry (liquids and polymers), biophysics, enzymology, molecular biology, pharmaceutical chemistry, genetic engineering and biotechnology.
This book provides an overview of the essential characteristics and clinical applications of therapeutic proteins against human diseases, including cancers, immune disorders, infections, and other diseases. It presents the latest advancements in protein engineering techniques for producing desirable therapeutic proteins. The book also covers the strategies used to formulate and deliver systemic therapeutic proteins, approved protein therapeutics and their targets, and pharmacogenetic biomarkers. Further, it discusses challenges associated with the clinical implications of therapeutic proteins, including safety, immunogenicity, protein stability, degradation, and efficacy. It illustrates the development of biosimilar antibodies, optimization strategies for producing biobetter antibodies, and presents fundamental concepts about biosuperior therapeutics. Lastly, it includes a discussion about protein-based vaccines against bacterial and viral infections.
This book discusses how biological molecules exert their function and regulate biological processes, with a clear focus on how conformational dynamics of proteins are critical in this respect. In the last decade, the advancements in computational biology, nuclear magnetic resonance including paramagnetic relaxation enhancement, and fluorescence-based ensemble/single-molecule techniques have shown that biological molecules (proteins, DNAs and RNAs) fluctuate under equilibrium conditions. The conformational and energetic spaces that these fluctuations explore likely contain active conformations that are critical for their function. More interestingly, these fluctuations can respond actively to external cues, which introduces layers of tight regulation on the biological processes that they dictate. A growing number of studies have suggested that conformational dynamics of proteins govern their role in regulating biological functions, examples of this regulation can be found in signal transduction, molecular recognition, apoptosis, protein / ion / other molecules translocation and gene expression. On the experimental side, the technical advances have offered deep insights into the conformational motions of a number of proteins. These studies greatly enrich our knowledge of the interplay between structure and function. On the theoretical side, novel approaches and detailed computational simulations have provided powerful tools in the study of enzyme catalysis, protein / drug design, protein / ion / other molecule translocation and protein folding/aggregation, to name but a few. This work contains detailed information, not only on the conformational motions of biological systems, but also on the potential governing forces of conformational dynamics (transient interactions, chemical and physical origins, thermodynamic properties). New developments in computational simulations will greatly enhance our understanding of how these molecules function in various biological events.
Advances in Protein Molecular and Structural Biology Methods offers a complete overview of the latest tools and methods applicable to the study of proteins at the molecular and structural level. The book begins with sections exploring tools to optimize recombinant protein expression and biophysical techniques such as fluorescence spectroscopy, NMR, mass spectrometry, cryo-electron microscopy, and X-ray crystallography. It then moves towards computational approaches, considering structural bioinformatics, molecular dynamics simulations, and deep machine learning technologies. The book also covers methods applied to intrinsically disordered proteins (IDPs)followed by chapters on protein interaction networks, protein function, and protein design and engineering. It provides researchers with an extensive toolkit of methods and techniques to draw from when conducting their own experimental work, taking them from foundational concepts to practical application. - Presents a thorough overview of the latest and emerging methods and technologies for protein study - Explores biophysical techniques, including nuclear magnetic resonance, X-ray crystallography, and cryo-electron microscopy - Includes computational and machine learning methods - Features a section dedicated to tools and techniques specific to studying intrinsically disordered proteins
Theranostics and Precision Medicine for the Management of Hepatocellular Carcinoma: Translational and Clinical Outcomes, Volume Three provides comprehensive information about ongoing research and clinical data on liver cancer. The book presents detailed descriptions about diagnostics and therapeutic options for easy understanding, with a focus on precision medicine approaches to improve treatment outcomes. This updated volume discusses topics such as clinical and safety assessment of HCC patients, liver transplantation as a therapeutic option, immunotherapy interventions, and image-based surveillance. In addition, it discusses immunohistology of HCC-enabled precision medicine and artificial intelligence for hepatocellular carcinomas. This is a valuable resource for cancer researchers, oncologists, graduate students, hepathologists and members of biomedical research who need to understand more about liver cancer to apply in their research work or clinical setting. - Provides best practices for the management of hepatocellular carcinoma in the clinical setting - Discusses emerging treatment approaches based on artificial intelligence and precision medicine tools and techniques - Brings updated information on international clinical trials for the treatment of HCC