Valerie Daggett

About

Valerie Daggett is a Professor of Bioengineering at the University of Washington. Her research focuses on performing realistic molecular modeling studies related to protein stability, function, and folding. She aims to understand the fundamental processes of protein folding, which is a critical and largely unsolved problem in molecular biology. Her work emphasizes the importance of protein conformation in biological function and explores the structural details of native folded proteins as well as the folding process itself. Her research has significant implications for biological processes such as protein degradation, translocation, aging, and human diseases including cancer and amyloid diseases. She employs computer simulation methods to delineate the forces involved in protein folding, given the limitations of experimental approaches in capturing structural transitions and interactions during folding. Additionally, her research extends to biomaterial and biosensor design, utilizing insights gained from structural, dynamics, and folding studies of globular proteins. Her interests also include the structural and dynamical consequences of amino acid mutations, hydrophobic hydration, force field and software development, and dynameomics.

Research topics

• Biology
• Biochemistry
• Chemistry
• Medicine
• Biophysics
• Pathology
• Organic chemistry
• Neuroscience
• Endocrinology
• Cell biology

Selected publications

• α-Sheet secondary structure in amyloid β-peptide drives aggregation and toxicity in Alzheimer’s disease

  Proceedings of the National Academy of Sciences · 2019-04-19 · 148 citations

  articleOpen accessSenior authorCorresponding

  Alzheimer’s disease (AD) is characterized by the deposition of β-sheet–rich, insoluble amyloid β-peptide (Aβ) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aβ oligomers adopt a nonstandard secondary structure, termed “α-sheet.” These oligomers form in the lag phase of aggregation, when Aβ-associated cytotoxicity peak…

  PublisherOA PDFDOI

• SOBA: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers

  Proceedings of the National Academy of Sciences · 2022 · 67 citations

  Senior authorCorresponding

  The formation of toxic Amyloid β-peptide (Aβ) oligomers is one of the earliest events in the molecular pathology of Alzheimer's Disease (AD). These oligomers lead to a variety of downstream effects, including impaired neuronal signaling, neuroinflammation, tau phosphorylation, and neurodegeneration, and it is estimated that these events begin 10 to 20 y before the presentation of symptoms. Toxic Aβ oligomers contain a nonstandard protein structure, termed α-sheet, and designed α-sheet peptides t…

  PublisherOA PDFDOI

• Visualizing Protein Folding and Unfolding

  Journal of Molecular Biology · 2019-03-03 · 53 citations

  reviewSenior authorCorresponding
  PublisherDOI

• Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin

  Proceedings of the National Academy of Sciences · 2019-05-20 · 46 citations

  articleOpen access

  The naturally occurring nucleotide 2-deoxy-adenosine 5'-triphosphate (dATP) can be used by cardiac muscle as an alternative energy substrate for myosin chemomechanical activity. We and others have previously shown that dATP increases contractile force in normal hearts and models of depressed systolic function, but the structural basis of these effects has remained unresolved. In this work, we combine multiple techniques to provide structural and functional information at the angstrom-nanometer a…

  PublisherOA PDFDOI

• Amyloid-β Oligomers: Multiple Moving Targets

  Biophysica · 2022 · 40 citations

  Senior authorCorresponding

  Alzheimer’s Disease (AD) is a neurodegenerative disorder that is characterized clinically by progressive cognitive decline and pathologically by the β-sheet rich fibril plaque deposition of the amyloid-β (Aβ) peptide in the brain. While plaques are a hallmark of AD, plaque burden is not correlated with cognitive impairment. Instead, Aβ oligomers formed during the aggregation process represent the main agents of neurotoxicity, which occurs 10–20 years before patients begin to show symptoms. These…

  PublisherOA PDFDOI

Recent grants

• NIH Grant R29GM050789

  NIH · $495k · 2000

• NIH Grant R01GM081407

  NIH · $1.1M · 2012

• Molecular Dynamics Simulations of Protein Unfolding

  NIH · $3.9M · 1995–2015

Frequent coauthors

• Alan R. Fersht

  University of Cambridge

  71 shared

• Darwin O. V. Alonso

  43 shared

• C. Mark Johnson

  University of Nottingham

  31 shared

• Hartmut Oschkinat

  Leibniz-Forschungsinstitut für Molekulare Pharmakologie

  20 shared

• José R. Pires

  Universidade Federal do Rio de Janeiro

  20 shared

• Matthew C. Childers

  20 shared

• Neil Ferguson

  18 shared

• Mari L. DeMarco

  Providence Health Care

  18 shared

Similar researchers at University of Washington

• Jesse Bloomh-117
• John Aitchisonh-81
• Frank DiMaioh-76