Scientific
Publications
AltPep’s science is rooted in the large body of work produced by the Daggett Research Group at the University of Washington.
Interested in the basis of our science? Browse the links below:
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
Experimental Studies of Designed α-Sheet Peptides
Nick, S., Bryers, J., Daggett, V., Layer-By-Layer Functionalized Gauze With Designed α-Sheet Peptides Inhibits E. coli and S. aureus Biofilm Formation, J Biomed Mater Res A, e37879 2025. https://pubmed.ncbi.nlm.nih.
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. https://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-β peptide drives aggregation and toxicity in Alzheimer’s disease, Proceedings of the National Academy of Sciences USA, 116, 8895-8900, 2019. https://doi.org/10.1073/pnas.182058511
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., De novo designed α-sheet peptides inhibit functional amyloid formation of Streptococcus mutans biofilms, J. Mol. Biol., 430, 3764-3773, 2018. https://doi: 10.1016/j.jmb.2018.07.005
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. https://doi: 10.1016/j.jmb.2018.06.043
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. https://pmc.ncbi.nlm.nih.gov/articles/PMC6153628/
Maris, N.L., Shea, D., Bleem, A., Bryers, J.D., Daggett, V., Chemical and physical variability in structural isomers of an L/D α-sheet peptide designed to inhibit amyloidogenesis, Biochemistry, 57: 507-510, 2018. https://doi.org/10.1021/acs.biochem.7b00345
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. https://doi.org/10.1038/s41522-017-0025-2
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. https://doi.org/10.1002/bit.26059
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. https://doi.org/10.1016/j.jmb.2016.03.013
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. https://doi.org/10.7554/eLife.01681
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. https://doi.org/10.1021/ml300478w
Tallon C., Pradel S., Yakabi K., Breyak E., Pascualy C., Tran C., Gajera C., Posakony J., Block G., Daggett V., Targeting of Aβ toxic oligomers via a designed peptide reduces plaque formation in an AD mouse model. CTAD 2025, Poster Presentation. San Diego, California. – View Poster Here.
Tallon C., Pradel S., Yakabi K., Breyak E., Tran C., Gajera C., Posakony J., Block G., Daggett V., Designed peptide increases clearance of Aβ toxic oligomers and inhibits plaque formation. AAIC 2025, Poster Presentation. Toronto, Canada. – View Poster Here.
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.
Characterizing the detailed conformational changes during the early stages of amyloidogenesis in different amyloid systems 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. https://doi.org/10.1111/jnc.14044
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. https://doi.org/10.4161/pri.27807
Chen, W., Van der Kamp, M.W., Daggett, V., Structural and dynamic properties of the human prion protein, Biophysical Journal, 106: 1152-1163, 2014. https://doi.org/10.1016/j.bpj.2013.12.053
Cheng, C.J., Daggett, V., Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH, Biomolecules, 4: 181-201, 2014. https://doi.org/10.3390/biom4010181
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. https://doi.org/10.1093/protein/gzt030
Scouras, A.D., Daggett, V., Disruption of the X-loop turn of the prion protein linked to scrapie resistance, Prot. Eng. Design. Sel., 25, 243-249, 2012. (Journal Cover) https://doi.org/10.1093/protein/gzs009
Van der Kamp, M.W., Daggett, V., 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. https://doi.org/10.1007/128_2011_158
Chen, W., Van der Kamp, M.W., Daggett V., Diverse effects on the native-sheet of the human prion protein due to disease-associated mutations, Biochemistry, 49, 9874-9881, 2010. https://doi.org/10.1021/bi101449f
Van der Kamp, M.W., Daggett, V., Pathogenic mutations in the hydrophobic core of the human prion protein can promote structural instability and misfolding, J. Mol. Biol., 404, 732-748, 2010. https://doi.org/10.1016/j.jmb.2010.09.060
Van der Kamp, M.W., Daggett, V., The influence of pH on the human prion protein: insights into the early steps of misfolding, Biophys. J., 99, 2289-2298, 2010. https://doi.org/10.1016/j.bpj.2010.07.063
Daggett V., Shedding light on amyloidosis with protein engineering, Protein Engineering Design & Selection, 22:445, 2009. https://doi.org/10.1093/protein/gzp049
Van der Kamp, M.W., Daggett, V., The consequences of pathogenic mutations to the human prion protein, Protein Engineering, Design and Selection, 22: 461-468, 2009. https://doi.org/10.1093/protein/gzp039
Schmidlin, T., Kennedy, B., Daggett, V., Structural changes to monomeric CuZn superoxide dismutase caused by the familial amyotrophic lateral sclerosis mutation A4V, Biophysical Journal, 97: 1709-1718, 2009. https://doi.org/10.1016/j.bpj.2009.06.043
DeMarco, M.L., Daggett, V., 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. https://doi.org/10.1111/j.1471-4159.2009.05892.x
Anderson, P.C., Daggett, V., 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. https://doi.org/10.1021/bi800677k
Scouras, A.D., Daggett, V., 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. https://doi.org/10.1007/s10853-008-2578-1
Steward, R.E., Armen, R.S., Daggett, V., Different disease-causing mutations in transthyretin accelerate the same conformational conversion, Protein Engineering Design and Selection, 21, 187-195, 2008. https://doi.org/10.1093/protein/gzm086
DeMarco, M.L., Daggett, V., Molecular mechanism for low pH-triggered misfolding of the human prion protein, Biochem., 46, 3045-3054, 2007. https://doi.org/10.1021/bi0619066
DeMarco, M.L., Silveira, J., Caughey, B., Daggett, V., Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models, Biochem., 45, 15573-15582, 2006. https://pubs.acs.org/doi/10.1021/bi0612723
Daggett, V., α-sheet: the toxic conformer in amyloid diseases?, Acc. Chem. Res., 39, 594-602, 2006. https://doi.org/10.1021/ar0500719
Armen, R.S., Daggett V., Characterization of two distinct β2-microglobulin unfolding intermediates that may lead to amyloid fibrils of different morphology, Biochem., 44, 16098-16107, 2005. https://doi.org/10.1021/bi050731h
Armen, R.S., Bernard, B., Day, R., Alonso, D.O.V., Daggett, V., Characterization of a possible amyloidogenic precursor in glutamine-repeat neurodegenerative diseases, Proc. Natl. Acad. Sci. USA, 102, 13433-13438, 2005. https://doi.org/10.1073/pnas.0502068102
DeMarco, M.L., Daggett, V., Local environmental effects on the structure of the prion protein, Comptes Rendus Biologies, 328, 847-862, 2005. https://doi.org/10.1016/j.crvi.2005.05.001
Bennion, B.J., DeMarco, M., Daggett, V., Preventing misfolding of the prion protein by trimethylamine N-oxide, Biochemistry, 43, 12955-12963, 2004. https://doi.org/10.1021/bi0486379
Armen, R.S., Alonso, D.O.V., Daggett, V., Anatomy of an amyloidogenic intermediate: conversion of β-sheet to α-pleated sheet structure in transthyretin at acidic pH, Structure, 12, 1847-1863, 2004. https://doi.org/10.1016/j.str.2004.08.005
Armen, R.S., DeMarco, M.L., Alonso, D.O.V., Daggett, V., 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. https://doi.org/10.1073/pnas.0401781101
First paper introducing α-sheet and its role in amyloidogenesis.
DeMarco, M.L., Daggett, V., From conversion to aggregation: protofibril formation of the prion protein, Proc. Natl. Acad. Sci. USA, 101, 2293-2298, 2004. https://doi.org/10.1073/pnas.0307178101
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., A.R. Fersht, The complete folding pathway of a protein from nanoseconds to microseconds, Nature, 421, 863-867, 2003. https://doi.org/10.1038/nature01428
Bennion, B.J., Daggett, V., Protein conformation and diagnostic tests: the prion protein, Clinical Chemistry, 48, 2105-2114, 2002. https://pubmed.ncbi.nlm.nih.gov/12446465/
Kazmirski, S.L., Isaacson, R.L., An, C., Buckle, A., Johnson, C.M., Daggett, V., A.R. Fersht, Loss of a metal-binding site in gelsolin leads to familial amyloidosis-Finnish type, Nat. Struct. Biol., 9 (2), 112-116, 2002. https://doi.org/10.1038/nsb745
Alonso, D.O.V., DeArmond, S., Cohen, F., Daggett, V., Mapping the early steps in the pH-induced conformational conversion of the prion protein, Proc. Natl. Acad. Sci. USA, 98, 2985-2989, 2001. https://doi.org/10.1073/pnas.061555898
DeArmond, S., Sanchez, H., Yehiely, F., Qiu, Y., Ninchak-Casey, A., Daggett, V., Paminano-Camerino, A.N., Cayetano, J., Rogers, M., Groth, D., Torchia, M., Tremblay, P., Scott, M.R., Cohen, F.E., Prusiner, S., Selective neuronal targeting in prion disease, Neuron, 19: 1337-1348, 1997. https://doi.org/10.1016/s0896-6273(00)80424-9
Kirshenbaum, K., Daggett, V., pH dependent conformations of the amyloid (1-28) peptide fragment explored using molecular dynamics, Biochemistry, 34: 7629-7639, 1995. https://doi.org/10.1021/bi00023a009
Kirshenbaum, K., Daggett, V., Sequence effects on the conformational properties of the (1-28) amyloid peptide fragment: testing a proposed mechanism for the α to β transition, Biochemistry, 34: 7640-7647, 1995. https://doi.org/10.1021/bi00023a010
Kazmirski, S., Alonso, D.O.V., Cohen, F.E., Prusiner, S., Daggett, V., 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. https://doi.org/10.1016/1074-5521(95)90049-7
Simulation methodology, design libraries and software critical for ‘discovery’ of α-sheet and design of α-sheet inhibitors.
Bromley, D., Rysavy, S.J., Su, R., Toofanny, R.D., Daggett, V., DIVE: A data intensive visualization engine, Bioinformatics, 30: 593-595, 2014. https://doi.org/10.1093/bioinformatics/btt721
Simms, A.M., Daggett, V., Protein simulation data in the relational model, J. of Supercomp., 62, 150-173, 2012. https://doi.org/10.1007/s11227-011-0692-3
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., Daggett, V., Dynameomics: a comprehensive database of protein dynamics, Structure, 18, 423-435, 2010. (Journal cover) https://doi.org/10.1016/j.str.2010.01.012
Beck, D.A.C., McCully, M.E., Alonso, D.O.V., Daggett V., 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., Daggett, V., 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. https://doi.org/10.1093/protein/gzn011
Simms, A.M., Toofanny, R.D., Kehl, C., Benson, N.C., Daggett, V., Dynameomics: design of a computational lab workflow and scientific data repository for protein simulations, Protein Engineering Design and Selection, 21, 369-377, 2008. https://doi.org/10.1093/protein/gzn012
Kehl, C.E., Simms, A.M., Toofanny, R.D., Daggett V., Dynameomics: A multi-dimensional analysis-optimized database for dynamic protein data, Protein Engineering Design and Selection, 21, 379-386, 2008. https://doi.org/10.1093/protein/gzn015
Beck, D.A.C., Bennion, B.J., Alonso, D.O.V., Daggett, V., 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. https://doi.org/10.1016/s0076-6879(07)28022-x
Beck, D.A.C., Daggett, V., Methods for molecular dynamics simulations of protein folding/unfolding in solution, Methods, 34, 112-120, 2004. https://doi.org/10.1016/j.ymeth.2004.03.008
Levitt, M., Hirshberg, M., Sharon, R., Laidig, K.E., Daggett, V., 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. https://pubs.acs.org/doi/10.1021/jp964020s
Levitt, M., Hirshberg, M., Sharon, R., Daggett, V., 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. https://doi.org/10.1016/0010-4655(95)00049-L
