Scientific Publications

Shea, D.; Daggett, V., Amyloid-β Oligomers: Multiple Moving Targets, Biophysica 2(2), 91-110, 2022; https://doi.org/10.3390/biophysica2020010

Prosswimmer T, Daggett V., The role of α-sheet structure in amyloidogenesis: characterization and implications, Open Biol.12: 220261, 2022; https://doi.org/10.1098/rsob.220261

Tallon, C., Gajera, C., Posakony, J., Block, G., Daggett, V., “Designed peptide targeting α-sheet Amyloid-β oligomers decreases toxic oligomer burden and improves behavior in AD mouse model.” CTAD 2023, Clinical Trials on Alzheimer’s Disease. Poster Presentation. Boston, Massachusetts.  – View Poster Here.

Chen, A., Shea, D. & Daggett, V. Performance of SOBA-AD blood test in discriminating Alzheimer’s disease patients from cognitively unimpaired controls in two independent cohorts. Sci Rep 14, 7946 (2024). https://doi.org/10.1038/s41598-024-57107-w

Prosswimmer, T., Heng, A., Daggett, V., Mechanistic insights into the role of amyloid-β in innate immunity, Scientific Reports, 14, Article number: 5376 (2024). https://doi.org/10.1038/s41598-024-55423-9

Hsu, C., Templin, A. Prosswimmer, T., Shea, D., Li, J., Brooks-Worrell, B., Kahn, S., Daggett, V., Human islet amyloid polypeptide-induced β-cell cytotoxicity is linked to formation of α-sheet structure, Protein Science, e4854 2023, https://doi.org/10.1002/pro.4854

Bleem, A., Prosswimmer, T., Chen, R., Hady, T., Li, J., Bryers, J., Daggett, V., Designed α-sheet peptides disrupt uropathogenic E. coli biofilms rendering bacteria susceptible to antibiotics and immune cells, Scientific Reports 13:9272, 2023. doi.org/10.1038/s41598-023-36343-6

Shea, D., Colasurado, E., Smith, A., Daggett, V., SOBA: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers, PNAS 119(50)e2213157119, 2022. https://doi.org/10.1073/pnas.2213157119

Shea, D., Hsu, C.-C., Bi, T., Paranjapye, N., Childers, M., Cochran, J., Tomberlin, C.P., Wang, L., Paris, D., Zonderman, J., Varani, G., Link, C., Mullan, M., Daggett, V., α-sheet secondary structure in amyloid ß-peptide drives aggregation and toxicity in Alzheimer’s Disease,  Proceedings of the National Academy of Sciences USA, 116, 8895-8900, 2019.

Paper showing α-sheet peptide inhibition (SOBIN) and detection (SOBA) of toxic oligomers AND demonstration that amyloid -peptide (A) contains α-sheet structure.

Paranjapye, N., Daggett, V. a-sheet peptides inhibit functional amyloid formation of Streptococcus mutans biofilms. J. Mol. Biol., 430, 3764-3773, 2018.

Bleem, A., Christiansen, G., Madsen, D.J. Maric, H. Stremgaard, K., Bryers, J.D., Daggett, V., Meyer, R.L. Otzen, D.E.  Protein engineering reveals mechanisms of functional amyloid formation in Pseudomonas aeruginosa biofilms. J. Mol. Biol., 430, 3751-3763, 2018.

Bi, T., Daggett, V. The role of α-sheet in amyloid oligomer aggregation and toxicity, Yale Journal of Biology and Medicine, 91, 247-255, 2018.

Maris, N.L., Shea, D., Bleem, A., Bryers, J.D., Daggett, V. Chemical and physical variability in structural isomers of an LID α-sheet peptide designed to inhibit amyloidogenesis. Biochemistry, 57: 507-510, 2018.

Bleem, A., Francisco, R., Bryers, J.D., Daggett, V. Designed α-sheet peptides suppress amyloid formation in Staphylococcus aureus biofilms, Nature Biofilms and Microbiomes, 3:16, 2017.

First example of α-sheet designs inhibiting amyloid formation in bacteria.

Bleem, A., Daggett, V. Structural and functional diversity among amyloid proteins: Agents of disease, building blocks of biology, and implications for molecular engineering. Biotechnology and Bioengineering, 114: 7-20, 2017.

Kellock, J., Hopping, G., Caughey, B., Daggett, V. Peptides composed of alternating L- and D- amino acids inhibit amyloidogenesis in three distinct amyloid systems independent of sequence. J. Mol. Biol., 428: 2317-2328, 2016.

Hopping, G., Kellock, J., Barnwal, R.P., Law, P., Bryers, J.D., Varani, G., Caughey, B., Daggett, V. Designed α-Sheet  Peptides Inhibit Amyloid Formation by Targeting Toxic Oligomers. eLIFE 3: e01681, 2014.

First experimental paper validating role of designed, synthetic α-sheet  peptides as inhibitors of amyloidogenesis through targeting of the toxic oligomers.

Hopping, G., Kellock, J., Caughey, B., Daggett, V. The designed trpzip-3 beta-hairpin inhibits amyloid formation in two different amyloid systems. ACS Medicinal Chemistry Letters, 4: 824-828, 2013.

Simulations of different amyloid systems mapping conformational changes during amyloidogenesis leading to discovery of α-sheet

Cheng, C.C., Koldse, H., Van der Kamp, M.W., Schiett, B., Daggett, V., Simulations of Membrane-bound Diglycosylated Human Prion Protein Reveal Potential Protective Mechanisms against Misfolding, Journal of Neurochemistry, 142: 171-182, 2017.

Cheng, C.J., Daggett, V. Different misfolding mechanisms converge on common conformational changes: Human prion protein pathogenic mutants Y218N and E196K. Prion 8: 1-11, 2014.

Chen, W., van der Kamp, M.W., Daggett, V. Structural and dynamic properties of the human prion protein. Biophysical Journal 106: 1152-1163, 2014.

Cheng, C.J., Daggett, V. Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH. Biomolecules 4: 181-201, 2014.

Schmidlin,  T.,  Ploeger,  K.,  Jonsson,  A.L.  Daggett,  V.  Early  steps  in  thermal  unfolding  of superoxide dismutase 1 are similar to the conformational changes associated with the ALS-associated A4V mutation. Protein Engineering, Design and Selection, 26: 503- 513, 2013.

Scouras, A.D. and V. Daggett, Disruption of the X-Loop Turn of the Prion Protein Linked to Scrapie Resistance, Prot. Eng. Design. Sel., 25, 243-249, 2012. (Journal Cover)

Van der Kamp, M.W. and V. Daggett, Molecular dynamics as an approach to study prion protein misfolding and the effect of pathogenic mutations, Topics in Current Chemistry, Special Prion Issue, J. Tatzelt, Editor, 1-29, 2011.

Chen, W., van der Kamp, M.W., and V. Daggett, Diverse Effects on the Native -Sheet of the Human Prion Protein due to Disease-Associated Mutations, Biochemistry, 49, 9874-9881, 2010.

van der Kamp, M.W. and V. Daggett. Pathogenic mutations in the hydrophobic core of the human prion protein can promote structural instability and misfolding. J. Mol. Biol., 404, 732-748, 2010.

Van der Kamp, M.W. and V. Daggett, The influence of pH on the human prion protein: Insights into the early steps of misfolding. Biophys. J., 99, 2289-2298, 2010.

Daggett V. Shedding light on amyloidosis with protein engineering. Protein Engineering Design & Selection 22:445, 2009.

Van der Kamp, M.W. and V. Daggett. The consequences of pathogenic mutations to the human prion protein. Protein Engineering, Design and Selection, 22: 461-468, 2009.

Schmidlin T., Kennedy B., and V. Daggett. Structural changes to monomeric CuZn Superoxide Dismutase caused by the familial Amyotrophic Lateral Sclerosis mutation A4V. Biophysical Journal, 97: 1709-1718, 2009.

DeMarco, M.L. and V. Daggett, Characterization of cell-surface prion protein relative to its recombinant analogue: Insights from molecular dynamics simulations of diglycosylated, membrane-bound human prion protein, J. Neuro. Chem., 109: 60-73, 2009.

Anderson, P.C. and V. Daggett. Molecular Basis for the Structural Instability of Human DJ-1 Induced by the L166P Mutation Associated with Parkinson’s Disease, Biochemistry, 47,9380-9393, 2008.

Scouras, A.D. and V. Daggett, Species Variation in PrPSc Protofibril Models, J. Materials Sci. Special volume on Nano- and micromechanical properties of hierarchical biological materials: Linking mechanics, chemistry and biology, edited by Markus Buehler, 43, 3625-3637, 2008.

Steward, R.E., Armen, R.S. and V. Daggett, Different disease-causing mutations in transthyretin accelerate the same conformational conversion, Protein Engineering Design and Selection, 21, 187-195, 2008.

DeMarco, M.L. and V. Daggett, Molecular Mechanism for Low pH-Triggered Misfolding of the Human Prion Protein, Biochem., 46, 3045-3054, 2007. 

DeMarco, M.L., Silveira, J., Caughey, B., and V. Daggett, Structural Properties of Prion Protein Protofibrils and Fibrils: An Experimental Assessment of Atomic Models, Biochem., 45, 15573-15582, 2006.

Daggett, V. α-sheet: The toxic conformer in amyloid diseases? Acc. Chem. Res., 39, 594-602, 2006.

Armen, R.S. and V. Daggett, 2-microglobulin may form amyloid through an α-pleated sheet intermediate, Biochem., 44, 16098-16107, 2005.

Armen, R.S., Bernard, B., Day, R., Alonso, D.O.V. and V. Daggett, Characterization of a possible amyloidogenic precursor in glutamine-repeat neurodegenerative diseases, Proc. Natl. Acad. Sci. USA, 102, 13433-13438, 2005.

DeMarco, M.L. and V. Daggett, Local Environmental Effects on the Structure of the Prion Protein, Comptes Rendus Biologies 328, 847-862, 2005.

Bennion, B.J., DeMarco, M. and V. Daggett, Preventing misfolding of the prion protein by Trimethylamine N-oxide, Biochemistry, 43, 12955-12963, 2004.

Armen, R.S., Alonso, D.O.V. and V. Daggett, Anatomy of an amyloidogenic intermediate: Conversion of -sheet to α-pleated sheet structure in transthyretin at acidic pH, Structure, 12, 1847-1863, 2004.

Armen, R.S., DeMarco, M.L., Alonso, D.O.V. and V. Daggett, Pauling and Corey’s  α-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease Proc. Natl. Acad. Sci. USA, 101, 11622-11627, 2004.

First paper introducing α-sheet and its role in amyloidogenesis

DeMarco, M.L. and V. Daggett, From Conversion to Aggregation: Protofibril Formation of the Prion Protein, Proc. Natl. Acad. Sci. USA, 101, 2293-2298, 2004.

Mayor, U., Johnson, C.M., Grossmann, J.G., Sato, S., Jas, G.S., Freund, S.M.V., Guydosh, N.R., Alonso, D.O.V., Daggett, V. and A.R. Fersht, The Complete Folding Pathway of a Protein from Nanoseconds to Microseconds, Nature, 421, 863-867, 2003.

Bennion, B.J. and Daggett, V. Protein Conformation and Diagnostic Tests: The Prion Protein, Clinical Chemistry, 48, 2105-2114, 2002.

Kazmirski, S.L., Isaacson, R.L., An, C., Buckle, A., Johnson, C.M., Daggett, V. and A.R. Fersht, Pinpointing the Cause of Familial Amyloidosis-Finnish Type (FAF): Identification of a Metal Binding Site in the Crystal Structure of Human Gelsolin Domain 2, Nat. Struct. Biol., 9 (2), 112-116, 2002.

Alonso, D.O.V., DeArmond, S., Cohen, F., and Daggett, V., Mapping the Early Steps in the Conversion of the Prion Protein, Proc. Natl. Acad. Sci. USA, 98, 2985-2989, 2001.

S. DeArmond, H. Sanchez, F. Yehiely, Y. Qiu, A. Ninchak-Casey, V. Daggett, A.N. Paminano- Camerino, J. Cayetano, M. Rogers, D. Groth, M. Torchia, P. Tremblay, M.R. Scott, F.E. Cohen and S. Prusiner. Selective Neuronal Targeting in Prion Disease, Neuron, 19: 1337-1348, 1997.

Kirshenbaum, K. and V. Daggett, pH Dependent Conformations of the Amyloid (1-28) Peptide Fragment Explored Using Molecular Dynamics, Biochemistry, 34: 7629-7639, 1995.

Kirshenbaum, K. and V. Daggett, Sequence Effects on the Conformational Properties of the (1-28) Amyloid Peptide Fragment: Testing a Proposed Mechanism for a Transitions, Biochemistry, 34: 7640-7647, 1995.

Kazmirski, S., D.O.V. Alonso, F.E. Cohen, S. Prusiner and V. Daggett. Theoretical Studies of Sequence Effects on the Conformational Properties of a Fragment of the Prion Protein: Implications for Scrapie Formation. Chemistry & Biology, 2: 305-315, 1995.

Bromley,  D.,  Rysavy,  S.J.,  Su,  R.,  Toofanny,  R.D.,  Daggett,  V.  DIVE:  A  data  intensive visualization engine. Bioinformatics  30: 593-595, 2014.

Simms, A.M. and V. Daggett, Protein simulation data in the relational model, J. of Supercomp., 62, 150-173, 2012.

Van der Kamp, M.W., Anderson, P.C., Beck, D.A.C., Benson, N.C., Jonsson, A.L., Merkley, E.D., Schaeffer, R.D., Scouras, A.D., Simms, A., Toofanny, R.D., and V. Daggett. Dynameomics: A comprehensive database of protein dynamics. Structure, 18, 423-435, 2010.  (Journal cover)

Beck, D.A.C., McCully, M., Alonso, D.O.V. and V. Daggett, in lucem molecular mechanics, ilmm, Molecular modeling package, Software, University of Washington, 2000-2021.

Beck, D.A.C., Jonsson, A.L., Schaeffer, D., Scott, K.A., Day, R., Toofanny, R.D., Alonso, D.O.V., and V. Daggett. Dynameomics: Mass annotation of protein dynamics and unfolding in water by high-throughput atomistic molecular dynamics simulations, Protein Engineering Design and Selection, 21, 353-368, 2008.

Simms, A.M, Toofanny, R.D., Kehl, C., Benson, N.C. and V. Daggett. Dynameomics: Design of a computational lab workflow and scientific data repository for protein simulations, Protein Engineering Design and Selection, 21, 369-377, 2008.

Kehl, C.E., Simms, A.M., Toofanny, R.D. and V. Daggett. Dynameomics: A multi-dimensional analysis-optimized database for dynamic protein data, Protein Engineering Design and Selection, 21, 379-386, 2008.

Beck, D.A.C., Bennion, B.J., Alonso, D.O.V. and V. Daggett, Simulations of Macromolecules in Protective and Denaturing Osmolytes: Properties of Mixed Solvent Systems and their Effects on Water and Protein Structure and Dynamics, Methods in Enzymology volume titled “Osmosensing and Osmosignaling,” edited by Dieter Haussinger and Helmut Sies, 428, 373-396, 2007.

Beck, D.A.C. and V. Daggett, Methods for Molecular Dynamics Simulations of Protein Folding I Unfolding in Solution, Methods, 34, 112-120, 2004.

Levitt, M. Hirshberg, R. Sharon, K.E. Laidig, and V. Daggett, Calibration and Testing of a Water Model for Simulation of the Molecular Dynamics of Proteins and Nucleic Acids in Solution, J. Phys. Chem., 101: 5051-5061, 1997.

Levitt, M. Hirshberg, R. Sharon, K.E. Laidig, and V. Daggett, Calibration and Testing of a Water Model for Simulation of the Molecular Dynamics of Proteins and Nucleic Acids in Solution, J. Phys. Chem., 101: 5051-5061, 1997.

Levitt, M. Hirshberg, R. Sharon, and V. Daggett, Potential Energy Function and Parameters for Simulations of the Molecular Dynamics of Proteins and Nucleic Acids in Solution, Computer Physics Commun. 91: 215-231, 1995.

Bromley,  D.,  Rysavy,  S.J.,  Su,  R.,  Toofanny,  R.D.,  Levitt, M. Hirshberg, R. Sharon, and V. Daggett, Potential Energy Function and Parameters for Simulations of the Molecular Dynamics of Proteins and Nucleic Acids in Solution, Computer Physics Commun. 91: 215-231, 1995.