Physics Of Protein Folding Misfolding And Intrinsic Disorder

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Physics of Protein Folding, Misfolding, and Intrinsic Disorder

Author : Prakash Kulkarni
Publisher : Mdpi AG
ISBN 13 : 9783036591124
Total Pages : 0 pages
Book Rating : 4.5/5 (911 download)

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Book Synopsis Physics of Protein Folding, Misfolding, and Intrinsic Disorder by : Prakash Kulkarni

Download or read book Physics of Protein Folding, Misfolding, and Intrinsic Disorder written by Prakash Kulkarni and published by Mdpi AG. This book was released on 2023-10-18 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Special Issue of Biomolecules, "Physics of Protein Folding, Misfolding, and Intrinsic Disorder: A Themed Issue in Honour of Professor Vladimir Uversky on the Occasion of His 60th Birthday", is a dedication to one of the discoverers of IDPs. This collection is a small token of the respect, admiration, and affection the contributors have for Prof. Vladimir (Volodya) Uversky. It is also a celebration of his illustrious career, and his accomplishments, and contributions to the IDP field that have inspired so many minds worldwide. This Special Issue presents the state of the art as it emerges from the contribution of the community of IDP researchers (IDPers), who have responded to the invitation to give credit to the pioneering work of Prof. Vladimir Uversky aimed at defining the class of disordered proteins and at promoting the attention of scientists toward the existence of "non-globular proteins". The papers in this collection show the advancement of our knowledge through the application of an integrative structural approach and witnesses at the same time the interest of the IDPer community toward new concepts (i.e., liquid-liquid phase separation) and new methodological frontiers (i.e., the application of machine learning and artificial intelligence to disorder prediction and modelling).

Intrinsically Disordered Proteins

Author : Vladimir N. Uversky
Publisher : Springer
ISBN 13 : 3319089218
Total Pages : 73 pages
Book Rating : 4.3/5 (19 download)

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Book Synopsis Intrinsically Disordered Proteins by : Vladimir N. Uversky

Download or read book Intrinsically Disordered Proteins written by Vladimir N. Uversky and published by Springer. This book was released on 2014-08-05 with total page 73 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this brief, Vladimir Uversky discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). Beginning with an introduction to the concept of protein intrinsic disorder, Uversky then goes on to describe the peculiar amino acid sequences of IDPs, their structural heterogeneity, typical functions and disorder-based binding modes. In the final sections, Uversky discusses IDPs in human diseases and as potential drug targets. This volume provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

Dancing protein clouds: Intrinsically disordered proteins in health and disease, Part A

Author :
Publisher : Academic Press
ISBN 13 : 0128168528
Total Pages : 424 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Dancing protein clouds: Intrinsically disordered proteins in health and disease, Part A by :

Download or read book Dancing protein clouds: Intrinsically disordered proteins in health and disease, Part A written by and published by Academic Press. This book was released on 2019-09-11 with total page 424 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Dancing protein clouds: Intrinsically disordered proteins in the norm and pathology" represents a set of selected studies on a variety of research topics related to intrinsically disordered proteins. Topics in this update include structural and functional characterization of several important intrinsically disordered proteins, such as 14-3-3 proteins and their partners, as well as proteins from muscle sarcomere; representation of intrinsic disorder-related concept of protein structure-function continuum; discussion of the role of intrinsic disorder in phenotypic switching; consideration of the role of intrinsically disordered proteins in the pathogenesis of neurodegenerative diseases and cancer; discussion of the roles of intrinsic disorder in functional amyloids; demonstration of the usefulness of the analysis of translational diffusion of unfolded and intrinsically disordered proteins; consideration of various computational tools for evaluation of functions of intrinsically disordered regions; and discussion of the role of shear stress in the amyloid formation of intrinsically disordered regions in the brain. Provides some recent studies on the intrinsically disordered proteins and their functions, as well as on the involvement of intrinsically disordered proteins in pthogenesis of various diseases Contains numerous illustrative materials (color figures, diagrams, and tables) to help the readers to delve in the information provided Includes contributions from recognized experts in the field

The Physics of Protein Structure and Dynamics

Author : Reinhard Schweitzer-Stenner
Publisher : Academic Press
ISBN 13 : 9780443159640
Total Pages : 0 pages
Book Rating : 4.1/5 (596 download)

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Book Synopsis The Physics of Protein Structure and Dynamics by : Reinhard Schweitzer-Stenner

Download or read book The Physics of Protein Structure and Dynamics written by Reinhard Schweitzer-Stenner and published by Academic Press. This book was released on 2024-09-01 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Physics of Protein Structure and Dynamics: When and Why Proteins Fold or Don’t Fold addresses an overlooked issue in current books in the field - folding, misfolding, and intrinsically disordered proteins (vide infra). The book looks at protein folding and intrinsically disordered proteins, which must be seen as heavily interrelated topics that need to be viewed together. The book also looks at the physics of protein/peptide aggregation. Since intrinsically disordered peptides and proteins play a major role particularly in aggregation and self-assembly processes that lead to various diseases (Alzheimer, Parkinson, Huntington, Mad-Cow), IDPs and protein self-assembly must be considered together. Moreover, protein aggregation cannot be separated from protein folding since it is frequently the product of misfolding. The proposed book will demonstrate the relationships between protein folding, non-folding and aggregation and emphasize the underlying physics.

Dancing Protein Clouds: Intrinsically Disordered Proteins in Health and Disease, Part B

Author :
Publisher : Academic Press
ISBN 13 : 0128226048
Total Pages : 402 pages
Book Rating : 4.1/5 (282 download)

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Book Synopsis Dancing Protein Clouds: Intrinsically Disordered Proteins in Health and Disease, Part B by :

Download or read book Dancing Protein Clouds: Intrinsically Disordered Proteins in Health and Disease, Part B written by and published by Academic Press. This book was released on 2020-08-19 with total page 402 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dancing Protein Clouds: Intrinsically Disordered Proteins in Health and Disease, Part B, represents a set of selected studies on a variety of research topics related to intrinsically disordered proteins. Topics in this update include structural and functional characterization of several important intrinsically disordered proteins, such as 14-3-3 proteins and their partners, as well as proteins from muscle sarcomere; representation of intrinsic disorder-related concept of protein structure-function continuum; discussion of the role of intrinsic disorder in phenotypic switching; consideration of the role of intrinsically disordered proteins in the pathogenesis of neurodegenerative diseases and cancer; discussion of the roles of intrinsic disorder in functional amyloids; demonstration of the usefulness of the analysis of translational diffusion of unfolded and intrinsically disordered proteins; consideration of various computational tools for evaluation of functions of intrinsically disordered regions; and discussion of the role of shear stress in the amyloid formation of intrinsically disordered regions in the brain. Provides some recent studies on the intrinsically disordered proteins and their functions, as well as on the involvement of intrinsically disordered proteins in pthogenesis of various diseases Contains numerous illustrative materials (color figures, diagrams, and tables) to help the readers to delve in the information provided Includes contributions from recognized experts in the field

Dancing Protein Clouds: Intrinsically Disordered Proteins in the Norm and Pathology, Part C

Author :
Publisher : Academic Press
ISBN 13 : 0323853005
Total Pages : 438 pages
Book Rating : 4.3/5 (238 download)

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Book Synopsis Dancing Protein Clouds: Intrinsically Disordered Proteins in the Norm and Pathology, Part C by :

Download or read book Dancing Protein Clouds: Intrinsically Disordered Proteins in the Norm and Pathology, Part C written by and published by Academic Press. This book was released on 2021-10-14 with total page 438 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dancing Protein Clouds: Intrinsically Disordered Proteins in the Norm and Pathology, Part C, Volume 183 represents a set of selected studies on a variety of research topics related to intrinsically disordered proteins. Topics in this volume include discussions on the evolution of disorder, consideration of the peculiarities of phase separation of the prion protein, a general discussion of the relationships between intrinsic disorder and protein functions, coverage of the structural and functional characterization of several important intrinsically disordered proteins, such as transcription factors, outer membrane porins, trans-membrane and membrane associated proteins with ID regions, discussion of molecular simulations of IDPs, and much more. Provides recent studies on the intrinsically disordered proteins and their functions, along with the involvement of intrinsically disordered proteins in the pathogenesis of various diseases Contains numerous illustrative materials (color figures, diagrams and tables) to help readers delve into the information provided Includes contributions from recognized experts in the field

Structure and Intrinsic Disorder in Enzymology

Author : Munishwar Nath Gupta
Publisher : Elsevier
ISBN 13 : 0323995349
Total Pages : 529 pages
Book Rating : 4.3/5 (239 download)

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Book Synopsis Structure and Intrinsic Disorder in Enzymology by : Munishwar Nath Gupta

Download or read book Structure and Intrinsic Disorder in Enzymology written by Munishwar Nath Gupta and published by Elsevier. This book was released on 2022-11-17 with total page 529 pages. Available in PDF, EPUB and Kindle. Book excerpt: Structure and Intrinsic Disorder in Enzymology offers a direct, yet comprehensive presentation of the fundamental concepts, characteristics and functions of intrinsically disordered enzymes, along with valuable notes and technical insights powering new research in this emerging field. Here, more than twenty international experts examine protein flexibility and cryo-enzymology, hierarchies of intrinsic disorder, methods for measurement of disorder in proteins, bioinformatics tools for predictions of structure, disorder and function, protein promiscuity, protein moonlighting, globular enzymes, intrinsic disorder and allosteric regulation, protein crowding, intrinsic disorder in post-translational, and much more. Chapters also review methods for study, as well as evolving technology to support new research across academic, industrial and pharmaceutical labs. Unifies the roles of intrinsic disorder and structure in the functioning of enzymes and proteins Examines a range of enzyme and protein characteristics, their relationship to intrinsic disorder, and methods for study Features chapter contributions from international leaders in the field

Structure and Function of Intrinsically Disordered Proteins

Author : Peter Tompa
Publisher : CRC Press
ISBN 13 : 1420078933
Total Pages : 362 pages
Book Rating : 4.4/5 (2 download)

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Book Synopsis Structure and Function of Intrinsically Disordered Proteins by : Peter Tompa

Download or read book Structure and Function of Intrinsically Disordered Proteins written by Peter Tompa and published by CRC Press. This book was released on 2009-11-18 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: The existence and functioning of intrinsically disordered proteins (IDPs) challenge the classical structure-function paradigm that equates function with a well-defined 3D structure. Uncovering the disordered complement of proteomes and understanding their functioning can extend the structure-function paradigm to herald new breakthroughs in drug dev

Protein and Peptide Folding, Misfolding, and Non-Folding

Author : Reinhard Schweitzer-Stenner
Publisher : John Wiley & Sons
ISBN 13 : 1118183355
Total Pages : 484 pages
Book Rating : 4.1/5 (181 download)

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Book Synopsis Protein and Peptide Folding, Misfolding, and Non-Folding by : Reinhard Schweitzer-Stenner

Download or read book Protein and Peptide Folding, Misfolding, and Non-Folding written by Reinhard Schweitzer-Stenner and published by John Wiley & Sons. This book was released on 2012-02-08 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sheds new light on intrinsically disordered proteins and peptides, including their role in neurodegenerative diseases With the discovery of intrinsically disordered proteins and peptides (IDPs), researchers realized that proteins do not necessarily adopt a well defined secondary and tertiary structure in order to perform biological functions. In fact, IDPs play biologically relevant roles, acting as inhibitors, scavengers, and even facilitating DNA/RNA-protein interactions. Due to their propensity for self-aggregation and fibril formation, some IDPs are involved in neurodegenerative diseases such as Parkinson's and Alzheimer's. With contributions from leading researchers, this text reviews the most recent studies, encapsulating our understanding of IDPs. The authors explain how the growing body of IDP research is building our knowledge of the folding process, the binding of ligands to receptor molecules, and peptide self-aggregation. Readers will discover a variety of experimental, theoretical, and computational approaches used to better understand the properties and function of IDPs. Moreover, they'll discover the role of IDPs in human disease and as drug targets. Protein and Peptide Folding, Misfolding, and Non-Folding begins with an introduction that explains why research on IDPs has significantly expanded in the past few years. Next, the book is divided into three sections: Conformational Analysis of Unfolded States Disordered Peptides and Molecular Recognition Aggregation of Disordered Peptides Throughout the book, detailed figures help readers understand the structure, properties, and function of IDPs. References at the end of each chapter serve as a gateway to the growing body of literature in the field. With the publication of Protein and Peptide Folding, Misfolding, and Non-Folding, researchers now have a single place to discover IDPs, their diverse biological functions, and the many disciplines that have contributed to our evolving understanding of them.

Protein Misfolding

Author : Rossen Donev
Publisher : Academic Press
ISBN 13 : 0128177500
Total Pages : 450 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Protein Misfolding by : Rossen Donev

Download or read book Protein Misfolding written by Rossen Donev and published by Academic Press. This book was released on 2020-01-17 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Misfolding, Volume 118, covers the wide spectrum of diseases and disorders that are attributed to protein misfolding, including degenerative and neurodegenerative, cardiovascular, renal, glaucoma, cancer, cystic fibrosis, Gaucher's disease, and many others. Specific chapters cover Mass spectrometric approaches for profiling protein folding and stability, Biomembranes, a key player in protein misfolding, how Genetic and environmental factors interact to disrupt proteostasis and trigger protein misfolding diseases, Formation of oligomers and large amorphous aggregates by intrinsically disordered proteins, Protein misfolding in ER stress with applications to cardiovascular and renal disease, and much more. Integrates methods for studying protein misfolding, factors that trigger this process and its role in a wide spectrum of diseases and disorders Contains timely chapters written by well-renowned authorities in their field Provides data that is well supported by a number of high quality illustrations, figures and tables, and targets a very wide audience of specialists, researchers and students

Intrinsically Disordered Proteins Studied by NMR Spectroscopy

Author : Isabella C. Felli
Publisher : Springer
ISBN 13 : 3319201646
Total Pages : 421 pages
Book Rating : 4.3/5 (192 download)

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Book Synopsis Intrinsically Disordered Proteins Studied by NMR Spectroscopy by : Isabella C. Felli

Download or read book Intrinsically Disordered Proteins Studied by NMR Spectroscopy written by Isabella C. Felli and published by Springer. This book was released on 2015-09-19 with total page 421 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). The properties of IDPs and IDPRs are highly complementary to those deriving from the presence of a unique and well-defined three-dimensional fold. Ignored for a long time in high-resolution studies of proteins, intrinsic protein disorder is now recognized as one of the key features for a large variety of cellular functions, where structural flexibility presents a functional advantage in terms of binding plasticity and promiscuity and this volume explores this exciting new research. Recent progress in the field has radically changed our perspective to study IDPs through NMR: increasingly complex IDPs can now be characterized, a wide range of observables can be determined reporting on the structural and dynamic properties, computational methods to describe the structure and dynamics are in continuous development and IDPs can be studied in environments as complex as whole cells. This volume communicates the new exciting possibilities offered by NMR and presents open questions to foster further developments. Intrinsically Disordered Proteins Studied by NMR Spectroscopy provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

Protein Folding, Misfolding, and Disease

Author : Andrew F. Hill
Publisher : Humana Press
ISBN 13 : 9781603272216
Total Pages : 0 pages
Book Rating : 4.2/5 (722 download)

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Book Synopsis Protein Folding, Misfolding, and Disease by : Andrew F. Hill

Download or read book Protein Folding, Misfolding, and Disease written by Andrew F. Hill and published by Humana Press. This book was released on 2011-07-01 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein misfolding is a key feature of many disorders in humans, given that over twenty proteins are known to misfold and cause disease. In Protein Folding, Misfolding, and Disease: Methods and Protocols, experts in the field present a collection of current methods for studying the analysis of protein folding and misfolding, featuring strategies for expressing and refolding recombinant proteins which can then be utilized in subsequent experiments. This detailed volume also covers methods for analyzing the formation of amyloid, protocols for determining the size and structure of native and misfolded proteins, as well as specific examples of where misfolded proteins can be examined using state-of –the-art technologies. Written in the highly successful Methods in Molecular BiologyTM series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Up to date and authoritative, Protein Folding, Misfolding, and Disease: Methods and Protocols offers researchers the tools necessary to move ahead in this vital field.

Protein Physics

Author : Alexei V. Finkelstein
Publisher : Elsevier
ISBN 13 : 0081012365
Total Pages : 528 pages
Book Rating : 4.0/5 (81 download)

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Book Synopsis Protein Physics by : Alexei V. Finkelstein

Download or read book Protein Physics written by Alexei V. Finkelstein and published by Elsevier. This book was released on 2016-06-22 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein Physics: A Course of Lectures covers the most general problems of protein structure, folding and function. It describes key experimental facts and introduces concepts and theories, dealing with fibrous, membrane, and water-soluble globular proteins, in both their native and denatured states. The book systematically summarizes and presents the results of several decades of worldwide fundamental research on protein physics, structure, and folding, describing many physical models that help readers make estimates and predictions of physical processes that occur in proteins. New to this revised edition is the inclusion of novel information on amyloid aggregation, natively disordered proteins, protein folding in vivo, protein motors, misfolding, chameleon proteins, advances in protein engineering & design, and advances in the modeling of protein folding. Further, the book provides problems with solutions, many new and updated references, and physical and mathematical appendices. In addition, new figures (including stereo drawings, with a special appendix showing how to use them) are added, making this an ideal resource for graduate and advanced undergraduate students and researchers in academia in the fields of biophysics, physics, biochemistry, biologists, biotechnology, and chemistry. Fully revised and expanded new edition based on the latest research developments in protein physics Written by the world's top expert in the field Deals with fibrous, membrane, and water-soluble globular proteins, in both their native and denatured states Summarizes, in a systematic form, the results of several decades of worldwide fundamental research on protein physics and their structure and folding Examines experimental data on protein structure in the post-genome era

Protein Misfolding and Disease

Author : Peter Bross
Publisher : Springer Science & Business Media
ISBN 13 : 1592593941
Total Pages : 317 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Protein Misfolding and Disease by : Peter Bross

Download or read book Protein Misfolding and Disease written by Peter Bross and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: For decades it has been known that structured conformations are important for the proper functioning of most cellular proteins. However, appreciation that protein folding to the functional conformations as well as the structural maintenance of protein molecules are very complex processes has only emerged during the last ten years. The intimate interplay uncovered by this scientific development led us to realize that perturbations of the protein folding process and disturbances of conformational maintenance are major disease mechanisms. This development has given rise to the concept of conformational diseases and the broader signature of protein folding diseases, comprising diseases in which mutations or environmental stresses may result in a partial misfolding that leads then to alternative conformations capable of disturbing cellular processes. This may happen by self-association (aggregation), as in prion and Alzheimer’s diseases, or by incorporation of alternatively folded subunits into structural entities, as in collagen diseases. Another possibility is that folding to the native structure is impaired or abolished, resulting in decreased stea- state levels of the correctly folded protein, as is observed in cystic fibrosis and 1-antitrypsin deficiency, as well as in many enzyme deficiencies. In addition, deficiencies of proteins that are engaged in assisting and supervising protein folding (protein quality control) may impair the folding of many other proteins, resulting in pathological phenotypes. Examples of this are the spastic paraplegia attributable to mutations in mitochondrial protease/chaperone complexes.

Protein Folding

Author : Grace E. Orellana
Publisher : American Chemical Society
ISBN 13 : 0841296383
Total Pages : 170 pages
Book Rating : 4.8/5 (412 download)

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Book Synopsis Protein Folding by : Grace E. Orellana

Download or read book Protein Folding written by Grace E. Orellana and published by American Chemical Society. This book was released on 2024-05-08 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt: Life as we know it would not exist if proteins did not fold into functional three-dimensional structures, where α-helices, loops, and β-sheets act together to form active sites that drive a myriad of biochemical reactions in the cell. The failure of this process is linked to the pathology of various diseases, such as neurodegenerative disorders like Alzheimer’s, genetic conditions (like cystic fibrosis), and cancer. It is no wonder that close to $2 billion in worldwide research funding has been devoted over the last five years (2019–2025) to helping scientists understand the molecular details of protein folding, how it can fail in ways that promote disease in humans, and clinical paths to treat or prevent diseases linked to protein misfolding. This primer is prerequisite reading to the literature on this important topic for readers new to the field. Chapter one provides exposure to the three-dimensional structure of proteins; readers will learn how to identify secondary structures, protein motifs, and domains involved in biological function. Chapter two introduces methodologies to determine the three-dimensional structure of proteins; readers will learn modern techniques to determine the secondary structure composition and the orientation of atoms in three-dimensional space. By providing exposure to how the physical environment (i.e., chemical denaturants, pH, pressure, and temperature) controls protein denaturation, readers will learn how such information can be used to study the biophysical characteristics of proteins through various probes and methodologies.

Protein Folding and Misfolding

Author : Heinz Fabian
Publisher : Springer Science & Business Media
ISBN 13 : 3642222307
Total Pages : 257 pages
Book Rating : 4.6/5 (422 download)

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Book Synopsis Protein Folding and Misfolding by : Heinz Fabian

Download or read book Protein Folding and Misfolding written by Heinz Fabian and published by Springer Science & Business Media. This book was released on 2011-09-18 with total page 257 pages. Available in PDF, EPUB and Kindle. Book excerpt: Infrared spectroscopy is a new and innovative technology to study protein folding/misfolding events in the broad arsenal of techniques conventionally used in this field. The progress in understanding protein folding and misfolding is primarily due to the development of biophysical methods which permit to probe conformational changes with high kinetic and structural resolution. The most commonly used approaches rely on rapid mixing methods to initiate the folding event via a sudden change in solvent conditions. Traditionally, techniques such as fluorescence, circular dichroism or visible absorption are applied to probe the process. In contrast to these techniques, infrared spectroscopy came into play only very recently, and the progress made in this field up to date which now permits to probe folding events over the time scale from picoseconds to minutes has not yet been discussed in a book. The aim of this book is to provide an overview of the developments as seen by some of the main contributors to the field. The chapters are not intended to give exhaustive reviews of the literature but, instead to illustrate examples demonstrating the sort of information, which infrared techniques can provide and how this information can be extracted from the experimental data. By discussing the strengths and limitations of the infrared approaches for the investigation of folding and misfolding mechanisms this book helps the reader to evaluate whether a particular system is appropriate for studies by infrared spectroscopy and which specific advantages the techniques offer to solve specific problems.

Protein Folding

Author : Cláudio M. Gomes
Publisher : Springer
ISBN 13 : 331900882X
Total Pages : 63 pages
Book Rating : 4.3/5 (19 download)

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Book Synopsis Protein Folding by : Cláudio M. Gomes

Download or read book Protein Folding written by Cláudio M. Gomes and published by Springer. This book was released on 2019-02-25 with total page 63 pages. Available in PDF, EPUB and Kindle. Book excerpt: This snapshot volume is designed to provide a smooth entry into the field of protein folding. Presented in a concise manner, each section introduces key concepts while providing a brief overview of the relevant literature. Outlook subsections will pinpoint specific aspects related to emerging methodologies, concepts and trends.