Misfoldedaggregatedproteinoncewasconsideredasinterestingasyesterday’strash—a bothersome by-product of important and productive activities, to be disposed of and forgotten as quickly as possible. Yesterday’s trash has become today’s focus of cons- erable scienti?c interest for at least two reasons: (1) protein aggregates are at the core of a number of chronic degenerative diseases such as Alzheimer’s disease, and (2) – gregation poses signi?cant obstacles to the manufacture of safe, ef?cacious, and stable protein products. As interest in protein misfolding, aggregation, and stability has soared beyond the core group of traditional protein-folding scientists, and as substantial scienti?c progress in understanding and controlling protein misfolding has been achieved, the need to summarize the state of the art became manifest. Although there are many excellent texts and edited collections on protein structure and folding, these volumes tend to relegate protein misfolding and aggregation to a minor role. Review articles and books focused on the biological role of protein aggregates in diseases have been published recently. Misbehaving Proteins: Protein (Mis)folding, Aggregation, and Stability differs from theseotherrecenteffortsinitsemphasisonfundamentalcomputationalandexperimental studies and in its linkage of disparate consequences of protein misfolding (e.g., from clinical manifestations to manufacturing headaches) to their common causes.
Innehållsförteckning
Protein Folding, Misfolding, Stability, and Aggregation.- Mathematical Models and Computational Methods.- Nonnative Protein Aggregation.- Simulations of Protein Aggregation.- Experimental Methods.- Elucidating Structure, Stability, and Conformational Distributions during Protein Aggregation with Hydrogen Exchange and Mass Spectrometry.- Application of Spectroscopic and Calorimetric Techniques in Protein Formulation Development.- Small-Angle Neutron Scattering as a Probe for Protein Aggregation at Many Length Scales.- Laser Light Scattering as an Indispensable Tool for Probing Protein Aggregation.- X-ray Diffraction for Characterizing Structure in Protein Aggregates.- Glass Dynamics and the Preservation of Proteins.- Fundamental Studies in Model Systems.- Folding and Misfolding as a Function of Polypeptide Chain Elongation.- Determinants of Protein Folding and Aggregation in P22 Tailspike Protein.- Factors Affecting the Fibrillation of ?-Synuclein, a Natively Unfolded Protein.- Molten Globule-Lipid Bilayer Interactions and Their Implications for Protein Transport and Aggregation.- Protein Product Development.- Self-Association of Therapeutic Proteins.- Mutational Approach to Improve Physical Stability of Protein Therapeutics Susceptible to Aggregation.
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