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? The links below provide more information.

Review Articles

Amyloid-β Oligomers: Multiple Moving Targets, Shea, D.; Daggett, V., Biophysica 20222(2), 91-110; https://doi.org/10.3390/biophysica2020010

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

 

Experimental Studies of Designed α-Sheet Peptides

 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.

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

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.

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.

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

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.

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.

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.

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

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

Characterizing the Detailed Conformational Changes during the Early Stages of Amyloidogenesis in Different Amyloid Systems leading to Discovery of α-Sheet

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

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.

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.

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.

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.

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

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.

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.

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

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.

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

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

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

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

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.

DeMarco, M.L. and V. Daggett, Molecular Mechanism for Low pH-Triggered Misfolding of the Human Prion Protein, Biochem., 46, 3045-3054, 2007. (Designated a ‘Hot Article’. The #17 most-accessed article in 2007)

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.

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.

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.

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.

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.

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.

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 influence of pH on the human prion protein: Insights into the early steps of misfolding. Biophys. J., 99, 2289-2298, 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.

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, 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.

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)

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.

Cheng, C.J., Daggett, V. Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH. Biomolecules 4: 181-201, 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. Different misfolding mechanisms converge on common conformational changes: Human prion protein pathogenic mutants Y218N and E196K. Prion 8: 1-11, 2014.

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.

Simulation Methodology, Design Libraries and Software Critical for 'Discovery' of α-Sheet and Design of α-Sheet Inhibitors

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.

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.

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

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., 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., 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.

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)

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.

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.

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.

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

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, 2000-2019.

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., 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.

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)

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