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: Amyloid-β Oligomers: Multiple Moving Targets
Experimental Studies of Designed α-Sheet Peptides

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

Paranjapye, N., Daggett, V. a-sheet peptides inhibit functional amyloid formation of Streptococcus mutans biofilms. J. Mol. Biol., 430, 3764-3773, 2018. De Novo Designed α-Sheet Peptides Inhibit Functional Amyloid Formation of Streptococcus mutans Biofilms – ScienceDirect

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. Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms – ScienceDirect

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. Focus: Medical Technology: The Role of α-sheet in Amyloid Oligomer Aggregation and Toxicity – PMC (nih.gov)

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. Chemical and Physical Variability in Structural Isomers of an L/D α-Sheet Peptide Designed To Inhibit Amyloidogenesis – PMC (nih.gov)

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 Designed α-sheet peptides suppress amyloid formation in Staphylococcus aureus biofilms – PubMed (nih.gov)

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. Peptides Composed of Alternating L- and D-Amino Acids Inhibit Amyloidogenesis in Three Distinct Amyloid Systems Independent of Sequence – ScienceDirect

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 Designed α-sheet peptides inhibit amyloid formation by targeting toxic oligomers | eLife (elifesciences.org)

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. Designed Trpzip-3 β-Hairpin Inhibits Amyloid Formation in Two Different Amyloid Systems – PMC (nih.gov)

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

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. Simulations of membrane‐bound diglycosylated human prion protein reveal potential protective mechanisms against misfolding – Cheng – 2017 – Journal of Neurochemistry – Wiley Online Library

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. Different misfolding mechanisms converge on common conformational changes – PMC (nih.gov)

Chen, W., van der Kamp, M.W., Daggett, V. Structural and dynamic properties of the human prion protein. Biophysical Journal 106: 1152-1163, 2014. Structural and Dynamic Properties of the Human Prion Protein – PMC (nih.gov)

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

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. 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 | Oxford Academic (oup.com)

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) Disruption of the X-loop turn of the prion protein linked to scrapie resistance – PMC (nih.gov)

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. Molecular dynamics as an approach to study prion protein misfolding and the effect of pathogenic mutations – PubMed (nih.gov)

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. Diverse Effects on the Native β-Sheet of the Human Prion Protein due to Disease-Associated Mutations – PMC (nih.gov)

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. Pathogenic Mutations in the Hydrophobic Core of the Human Prion Protein Can Promote Structural Instability and Misfolding – ScienceDirect

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. Influence of pH on the Human Prion Protein: Insights into the Early Steps of Misfolding (cell.com)

Daggett V. Shedding light on amyloidosis with protein engineering. Protein Engineering Design & Selection 22:445, 2009. Shedding light on amyloidosis with protein engineering – PubMed (nih.gov)

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. consequences of pathogenic mutations to the human prion protein | Protein Engineering, Design and Selection | Oxford Academic (oup.com)

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. Structural Changes to Monomeric CuZn Superoxide Dismutase Caused by the Familial Amyotrophic Lateral Sclerosis-Associated Mutation A4V – ScienceDirect

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. Characterization of cell-surface prion protein relative to its recombinant analogue: insights from molecular dynamics simulations of diglycosylated, membrane-bound human prion protein – PubMed (nih.gov)

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. Molecular Basis for the Structural Instability of Human DJ-1 Induced by the L166P Mutation Associated with Parkinson’s Disease | Biochemistry (acs.org)

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. Species variation in PrPSc protofibril models (fao.org)

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. Different disease-causing mutations in transthyretin trigger the same conformational conversion | Protein Engineering, Design and Selection | Oxford Academic (oup.com)

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) Molecular Mechanism for Low pH Triggered Misfolding of the Human Prion Protein | Biochemistry (acs.org)

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. Structural Properties of Prion Protein Protofibrils and Fibrils:  An Experimental Assessment of Atomic Models | Biochemistry (acs.org)

Daggett, V. α-sheet: The toxic conformer in amyloid diseases? Acc. Chem. Res., 39, 594-602, 2006. Alpha-sheet: The toxic conformer in amyloid diseases? – PubMed (nih.gov)

Armen, R.S. and V. Daggett, 2-microglobulin may form amyloid through an α-pleated sheet intermediate, Biochem., 44, 16098-16107, 2005. Characterization of Two Distinct β2-Microglobulin Unfolding Intermediates that May Lead to Amyloid Fibrils of Different Morphology | Biochemistry (acs.org)

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. Characterization of a possible amyloidogenic precursor in glutamine-repeat neurodegenerative diseases – PMC (nih.gov)

DeMarco, M.L. and V. Daggett, Local Environmental Effects on the Structure of the Prion Protein, Comptes Rendus Biologies 328, 847-862, 2005. Local environmental effects on the structure of the prion protein – ScienceDirect

Bennion, B.J., DeMarco, M. and V. Daggett, Preventing misfolding of the prion protein by Trimethylamine N-oxide, Biochemistry, 43, 12955-12963, 2004. Preventing Misfolding of the Prion Protein by Trimethylamine N-Oxide | Biochemistry (acs.org)

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. Anatomy of an Amyloidogenic Intermediate: Conversion of β-Sheet to α-Sheet Structure in Transthyretin at Acidic pH – ScienceDirect

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 Pauling and Corey’s α-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease – PMC (nih.gov)

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. From conversion to aggregation: Protofibril formation of the prion protein – PMC (nih.gov)

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. The complete folding pathway of a protein from nanoseconds to microseconds – PubMed (nih.gov)

Bennion, B.J. and Daggett, V. Protein Conformation and Diagnostic Tests: The Prion Protein, Clinical Chemistry, 48, 2105-2114, 2002. Protein Conformation and Diagnostic Tests: The Prion Protein | Clinical Chemistry | Oxford Academic (oup.com)

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. Loss of a metal-binding site in gelsolin leads to familial amyloidosis-Finnish type – PubMed (nih.gov)

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. Mapping the early steps in the pH-induced conformational conversion of the prion protein – PMC (nih.gov)

  1. 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. Selective neuronal targeting in prion disease – PubMed (nih.gov)

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. Theoretical studies of sequence effects on the conformational properties of a fragment of the prion protein: implications for scrapie formation – ScienceDirect

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. Sequence effects on the conformational properties of the amyloid beta (1-28) peptide: testing a proposed mechanism for the alpha–>beta transition – PubMed (nih.gov)

Kirshenbaum, K. and V. Daggett, pH Dependent Conformations of the Amyloid (1-28) Peptide Fragment Explored Using Molecular Dynamics, Biochemistry, 34: 7629-7639, 1995. pH-dependent conformations of the amyloid beta(1-28) peptide fragment explored using molecular dynamics – PubMed (nih.gov)

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. DIVE: a data intensive visualization engine – PMC (nih.gov)

Simms, A.M. and V. Daggett, Protein simulation data in the relational model, J. of Supercomp., 62, 150-173, 2012. Protein Simulation Data in the Relational Model – PMC (nih.gov)

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. Dynameomics: a multi-dimensional analysis-optimized database for dynamic protein data – PubMed (nih.gov)

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. Dynameomics: design of a computational lab workflow and scientific data repository for protein simulations – PubMed (nih.gov)

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. Dynameomics: mass annotation of protein dynamics and unfolding in water by high-throughput atomistic molecular dynamics simulations – PubMed (nih.gov)

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. Simulations of Macromolecules in Protective and Denaturing Osmolytes: Properties of Mixed Solvent Systems and Their Effects on Water and Protein Structure and Dynamics – ScienceDirect

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. Methods for molecular dynamics simulations of protein folding/unfolding in solution – ScienceDirect

Beck, D.A.C. and V. Daggett, Methods for Molecular Dynamics Simulations of Protein Folding I Unfolding in Solution, Methods, 34, 112-120, 2004. Methods for molecular dynamics simulations of protein folding/unfolding in solution – ScienceDirect

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. Calibration and Testing of a Water Model for Simulation of the Molecular Dynamics of Proteins and Nucleic Acids in Solution | The Journal of Physical Chemistry B (acs.org)

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. Potential energy function and parameters for simulations of the molecular dynamics of proteins and nucleic acids in solution – ScienceDirect

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. Potential energy function and parameters for simulations of the molecular dynamics of proteins and nucleic acids in solution – ScienceDirect