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 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.

The book will discuss classes of proteins and their folding, as well as the involvement of bioinformatics in solving the protein folding problem. In vivo and in vitro folding mechanisms are examined, as well as the failures of in vitro folding, a mechanism helpful in understanding disease caused by misfolding. The role of energy landscapes is also discussed and the computational approaches to these landscapes.

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.

The Physics of Protein Structure and Dynamics looks at various aspects of protein structure and dynamics from a physico-chemical point of view. It goes into some depth regarding the description of non-covalent forces that determine the relative stability of folded and unfolded proteins. Anharmonic protein dynamics involving motions between different minima of a rugged Gibbs energy landscape is described in great detail. The book combines various aspects of the protein folding/unfolding processes with an overview of intrinsically disordered proteins, which have attracted considerable interest of the protein community over the last 25 years but are thus far underrepresented in classroom-oriented textbooks. The book looks at protein folding and intrinsically disordered proteins as heavily interrelated topics that need to be viewed together. Furthermore, it presents some basic physico-chemical aspects of protein/peptide self-assembly into nanoscale fibrils. 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). Therefore, the relevance of protein disorder for protein self-assembly deserves a closer look. Protein self-assembly cannot be separated from protein folding since it is frequently the product of misfolding. With regard to modern theories, the folding processes are linked to insights on protein dynamics and the discovered relationship between proteins and spin glasses. - The readers will benefit from being provided with an in-depth overview of the physical concepts that govern different aspects of protein folding, disorder and self-assembly. By emphasizing the relationship between these issues, the approach adds a holistic character to the book - The book is to a major extent mathematically based. Mathematics is part of the language of physicists and physical chemists which cannot be properly substituted by words - For instructors, the book will offer a unique source for her/his teaching of current protein physics issues - The way how the book will be constructed (multiple references to primary literature with DOI links, literature-based problem sets and topics for discussion) will facilitate a learning process suitable for research-oriented students - Problem solving frequently requires the writing of short computer programs, something that is underemphasized in chemistry and biochemistry education (with the exception of computationally trained students, of course)

Protein folding and aggregation is the process by which newly synthesized proteins fold into the specific three-dimensional structures defining their biologically active states. It has always been a major focus of research in biochemistry and has often been seen as the unsolved second part of the genetic code. In the last 10 years we have witnessed a quantum leap in the research in this exciting area. Computational methods have improved to the extent of making possible to simulate the complete folding process of small proteins and the early stages of protein aggregation. Experimental methods have evolved to permit resolving fast processes of folding reactions and visualizing single molecules during folding. The findings from these novel experiments and detailed computer simulations have confirmed the main predictions of analytical theory of protein folding. In summary, protein folding research has finally acquired the status of a truly quantitative science, paving the way for more exciting developments in the near future. This unique book covers all the modern approaches and the many advances experienced in the field during the last 10 years. There is also much emphasis on computational methods and studies of protein aggregation which have really flourished in the last decade. It includes chapters in the areas that have witnessed major developments and are written by top experts including:computer simulations of folding, fast folding, single molecule spectroscopy, protein design, aggregation studies (both computational and experimental). Readers will obtain a unique perspective of the problems faced in the biophysical study of protein conformational behaviour in aqueous solution and how these problems are being solved with a multidisciplinary approach that combines theory, experiment and computer simulations. Protein Folding, Misfolding and Aggregation Classical Themes and Novel Approaches is essential reading for graduate students actively involved in protein folding research, other scientists interested in the recent progress of the field and instructors revamping the protein folding section of their biochemistry and biophysics courses.

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.