Misbehaving Proteins

1. Front Matter

   Pages I-VIII

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2. Introduction

   1. Front Matter

      Pages I-VIII

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   2. Protein Folding, Misfolding, Stability, and Aggregation

      • Regina M. Murphy, Amos M. Tsai

      Pages 3-13

3. Mathematical Models and Computational Methods

   1. Front Matter

      Pages I-VIII

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   2. Nonnative Protein Aggregation

      • Christopher J. Roberts

      Pages 17-46

   3. Simulations of Protein Aggregation

      • Carol K. Hall, Hung D. Nguyen, Alexander J. Marchut, Victoria Wagoner

      Pages 47-77

4. Experimental Methods

   1. Front Matter

      Pages I-VIII

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   2. Elucidating Structure, Stability, and Conformational Distributions during Protein Aggregation with Hydrogen Exchange and Mass Spectrometry

      • Erik J. Fernandez, Scott A. Tobler

      Pages 81-98

   3. Application of Spectroscopic and Calorimetric Techniques in Protein Formulation Development

      • Angela Wilcox, Rajesh Krishnamurthy

      Pages 99-123

   4. Small-Angle Neutron Scattering as a Probe for Protein Aggregation at Many Length Scales

      • Susan Krueger, Derek Ho, Amos Tsai

      Pages 125-146

   5. Laser Light Scattering as an Indispensable Tool for Probing Protein Aggregation

      • Regina M. Murphy, Christine C. Lee

      Pages 147-165

   6. X-ray Diffraction for Characterizing Structure in Protein Aggregates

      • Hideyo Inouye, Deepak Sharma, Daniel A. Kirschner

      Pages 167-191

   7. Glass Dynamics and the Preservation of Proteins

      • Christopher L. Soles, Amos M. Tsai, Marcus T. Cicerone

      Pages 193-214

5. Fundamental Studies in Model Systems

   1. Front Matter

      Pages I-VIII

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   2. Folding and Misfolding as a Function of Polypeptide Chain Elongation

      • Silvia Cavagnero, Nese Kurt

      Pages 217-245

   3. Determinants of Protein Folding and Aggregation in P22 Tailspike Protein

      • Matthew J. Gage, Brian G. Lefebvre, Anne S. Robinson

      Pages 247-264

   4. Factors Affecting the Fibrillation of α-Synuclein, a Natively Unfolded Protein

      • Anthony L. Fink

      Pages 265-285

   5. Molten Globule-Lipid Bilayer Interactions and Their Implications for Protein Transport and Aggregation

      • Lisa A. Kueltzo, C. Russell Middaugh

      Pages 287-309

6. Protein Product Development

   1. Front Matter

      Pages I-VIII

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   2. Self-Association of Therapeutic Proteins

      • Mary E. M. Cromwell, Chantal Felten, Heather Flores, Jun Liu, Steven J. Shire

      Pages 313-330

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.

• Polypeptide
• mutation
• protein
• protein folding
• protein sequence
• proteins
• transport
• Proteomics
• biochemical engineering

• Department of Chemical and Biological Engineering, University of Wisconsin, Madison, USA

  Regina M. Murphy

• Human Genome Sciences, Rockville, USA

  Amos M. Tsai

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