Publications

We do research at the interface of biology and physics. Our current projects involve the molecular-genetic study of the evolution of multicellularity, protein misfolding in neurodegenerative disease, and more recently, viral evolution and molecular therapeutics to SARS-CoV-2. Publications are listed here. (For Patents please see below.)

Papers:

• McAlary L, Nan JR, Shyu, C, Mine Sher M, Plotkin SS, Cashman NR, “Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells” (submitted)
• Garg P, Hsueh SCC, Plotkin SS, “Predicting the feasibility of targeting a conserved region on the S2 domain of the SARS-CoV-2 spike protein” (in review)
• Hsueh SCC and Plotkin SS, “Reservoir-REMD facilitates kinetic rescue from metastable peptide conformations” (in review)
• Pokrishevsky E, DuVal MG, McAlary L, Louadi S, Pozzi S, Roman A, Plotkin SS, Dijkstra A, Julien JP, Allison WT, Cashman NR “Tryptophan Residues in TDP-43 and SOD1 Mediate the Cross-seeding and Toxicity of SOD1” (submitted)
• Hsueh SCC, Nijland M, Aina A; Plotkin SS, “Cyclization Scaffolding for Improved Vaccine Immunogen Stability: Application to Tau Protein in Alzheimer’s Disease” Journal of Chemical Information and Modeling (2024)
• Zhao B, Cowan CM, Coutts J, Christy DD, Saraph A, Hsueh SCC, Plotkin SS, Mackenzie IR, Kaplan JM, Cashman NR, “Targeting RACK1 to alleviate TDP-43 and FUS proteinopathy-mediated suppression of protein translation and neurodegeneration” Acta Neuropathologica Communications 11, Article number: 200 (2023)
• DuVal MG, McAlary L, Habibi M, Garg P, Sher M, Cashman NR, Allison WT, and Plotkin SS “Physical Properties of Novel Aggressive and Beneficial SOD1 Mutants Predict Phenotypes Consistent with ALS” (submitted on bioRxiv 474585)
• Aina A, Hsueh SCC, Gibbs E, Peng X, Cashman NR, Plotkin SS “De novo computational design of a β-helix tau protein scaffold: An oligomer-selective vaccine immunogen candidate for Alzheimer’s disease” ACS Chem. Neurosci. 14, 15, 2603–2617 (2023)
• Aina A, Hsueh,SCC, Plotkin SS “PROTHON: A local order parameter-based method for efficient comparison of protein ensembles” J. Chem. Inf. Model. 63, 11, 3453–3461 (2023)
• Hsueh SCC, Aina A, Plotkin SS, “Ensemble Generation for Linear and Cyclic Peptides Using a Reservoir Replica Exchange Molecular Dynamics Implementation in GROMACS” J Phys Chem B, 26, 49, 10384–10399(2022) Cover article
• McAlary L, Shephard, VK, Sher M, Rice LJ, Yerbury JJ, Cashman NR, Plotkin SS “Assessment of protein inclusions in cultured cells using automated image analysis” STAR Protocols 3 (4), 101748 (2022)
• Gibbs E, Zhao B, Roman A, Plotkin SS, Peng X, Hsueh SCC, Aina A, Wang A, Shyu C, Yip CK, Nam S, Kaplan JM, Cashman NR “Rational Generation of Monoclonal Antibodies Selective for Pathogenic Forms of Alpha-Synuclein” Biomedicines, 10, 2168 (2022)
• Garg P, Semmler S, Baudouin C, Vande Velde C, Plotkin SS “Misfolding-Associated Exposure of Natively Buried Residues in Mutant SOD1 Facilitates Binding to TRAF6” Journal of Molecular Biology, Vol 434, Issue 6 (2022)
• Hsueh SCC, Nijlad M, Peng X, Hilton B, Plotkin SS, “First Principles Calculation of Protein–Protein Dimer Affinities of ALS-Associated SOD1 Mutants” Front. Mol. Biosci. 9:845013 (2022)
• Hsueh SCC, Aina A, Roman AY, Cashman, NR, Peng X, Plotkin SS “Optimizing Epitope Conformational Ensembles Using α-Synuclein Cyclic Peptide “Glycindel” Scaffolds: A Customized Immunogen Method for Generating Oligomer-Selective Antibodies for Parkinson’s Disease” ACS Chem. Neurosci., 13, 2261−2280 (2022)
• Peng X, Gibbs, E, Silverman JM, Cashman NR, and Plotkin SS “A Method for Systematically Ranking Therapeutic Drug Candidates Using Multiple Uncertain Screening Criteria” Statistical Methods in Medical Research Vol 30, Issue 6, page(s): 1502-1522 (2021)
• Plotkin SS, Cashman NR “Passive Immunotherapies targeting Aβ and Tau in Alzheimer’s disease” Neurobiology of Disease, Special Issue: Antibody Therapies v144 105010 (2020)
• Wright G, Watanabe TF, Amporndanai K, Plotkin SS, Cashman NR, Antonyuk SV, Hasnain SS, “Purification and Structural Characterization of Aggregation-Prone Human TDP-43 Involved in Neurodegeneratie Diseases” iScience 23 101159 (2020)
• Semmler S, Gagné M, Garg P, Pickles SR, Baudouin C, Hamon-Keromen E, Destroismaisons L, Khalfallah Y, Chaineau M, Caron E, Bayne AN, Trempe JF, Cashman NR, Star AT, Haqqani AS, Durcan TM, Meiering E, Robertson J, Grandvaux N, Plotkin SS, McBride HM, and Vande Velde C “TNF receptor–associated Factor 6 Interacts with ALS-linked Misfolded Superoxide Dismutase 1 and Promotes Aggregation“ The Journal of Biological Chemistry 295 3808-3825 (2020)
• Pataer A, Ozpolat B, Shao R, Cashman NR, Plotkin SS, Samuel CE, Lin S, Kabil N, Wang J, Majidi M, Vaporciyan A, Wistuba I, Hung MC, Swisher S, Fang B, Roth JA “Therapeutic Targeting of the PI4K2A/PKR Lysosome Network is Critical for Misfolded Protein Clearance and Survival in Cancer Cells” Oncogene 39 801-813 (2020)
• McAlary L, Plotkin SS, Yerbury J, Cashman NR “Prion-like Propagation of Protein Misfolding and Aggregation in Amyotrophic Lateral Sclerosis” Frontiers in Molecular Neuroscience 12, Article 262 (2019)
• McAlary L, Plotkin SS, Cashman NR “Emerging developments in targeting proteotoxicity in neurodegenerative diseases” CNS Drugs 33 883-904, doi.org/10.1007/s40263-019-00657-9 (2019)
• Gibbs E, Silverman JM, Zhao B, Peng X, Wang J, Wellington, CL, Mackenzie IR, Plotkin SS, Kaplan J, Cashman NR “A Rationally Designed Humanized Antibody Selective for Amyloid Beta Oligomers in Alzheimer’s Disease” Scientific Reports 9, Article 9870 (2019)
• Farrawell N, Yerbury M, Plotkin SS, McAlary L, Yerbury J “CuATSM Protects Against the Toxicity of Wild Type-like SOD1 Mutants But Not Mutants That Disrupt Metal Binding” ACS Chemical Neuroscience, 10 (3), 1555-1564 (2019)
• Peng X, Cashman NR and Plotkin SS “Prediction of Misfolding-Specific Epitopes in SOD1 Using Collective Coordinates” J Phys Chem B, William A. Eaton Festschrift Special Issue (2018)
• Dupuis JH, Yu, H, Habibi M, Peng X, Plotkin SS, Wang S, Song C, Yada RY “pH Dependant Membrane Binding of the Solanum tuberosum Plant Specific Insert” BBA – Biomembranes 1860 pp 2608–2618 (2018)
• Silverman JM, Gibbs E, Martens KM, Balducci C, Peng X, Wang J, Yousefi M, Cowan CM, Lamour G, Louadi A, Ban Y, Robert J, Stukas S, Forloni G, Hsiung GR, Plotkin SS, Wellington CL and Cashman NR “A Rational Structured Epitope Defines a Distinct Subclass of Toxic Amyloid-beta Oligomers” ACS Chem. Neurosci 9 (7), 1591-1606 (2018)
• Habibi M, Plotkin SS and Rottler J “Soft Vibrational Modes Predict Force-induced Protein Unfolding Mechanisms” Biophysical Journal, 114 (3) pp 562-569 (2018)
• Habibi M, Rottler J and Plotkin SS “The Unfolding Mechanism of Monomeric Mutant SOD1 by Simulated Force Spectroscopy“, Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics, Volume 1865, Issue 11, Part B, (2017)
• Habibi M, Rottler J and Plotkin SS “As Simple as Possible but not Simpler: Exploring the Fidelity of Coarse-Grained Protein Models for Simulated Force Spectroscopy”, PLoS Comput Biol 12(11): e1005211 (2016)
• Mills EA, Plotkin SS “Protein Transfer Free Energy Obeys Entropy-Enthalpy Compensation“  J. Phys. Chem. B.119 (44), pp14130–14144 (2015).
• Grad LI, et al “Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms” Proc. Natl. Acad. Sci. USA 111, 3620-3625 (2014) http://www.pnas.org/content/111/9/3620.full.pdf+html?with-ds=yes
• Chen S, Witt DM, Plotkin SS “Quantizing models of (2+1)-dimensional gravity on non-orientable manifolds” Classical Quant. Grav. 31 (2014) 055008  CQG+ News & views
• Mills EA and Plotkin SS “Density Functional Theory for Protein Transfer Free Energies” J. Phys. Chem. B (2013) 117 (42) 13278–13290
• Das A, Sin BK, Mohazab AR, and Plotkin SS  “Unfolded protein ensembles, folding trajectories, and refolding rate prediction” J. Chem. Phys. 139, 121925 (2013)
• Mohazab AR, Plotkin SS “Polymer Uncrossing and Knotting in Protein Folding, and Their Role in Minimal Folding Pathways” PLoS ONE 8(1): e53642 (2013)
• Das A, Plotkin SS “Mechanical Probes of SOD1 Predict Systematic Trends in Metal and Dimer Affinity of ALS-Associated Mutants” J. Mol. Biol. 425, 850–874 (2013)
• Das A, Plotkin SS “SOD1 Exhibits Allosteric Frustration to Facilitate Metal Binding Affinity” Proc. Natl. Acad. Sci. USA 110, 3871 (2013)
• Chen S, Plotkin SS “Statistical Mechanics of Graph Models and their Implications for Emergent Spacetime Manifolds” Phys Rev D 87, 084011 (2013)
• Grad LI, Guest W, Yanai A, Pokrishevsky E, O’Neill MA, Gibbs E, Semenchenko V, Yousefi M, Wishart DS, Plotkin SS, Cashman NR, “Intermolecular Transmission of Superoxide Dismutase 1 Misfolding in Living Cells” Proc. Natl. Acad. Sci, 108, 16398–16403 (2011) (with supp mat)
• Hadizadeh S, Linhananta A, Plotkin SS, “Improved Measures for the Shape of a Disordered Polymer to Test a Mean-field Theory of Collapse” Macromolecules, 44, 6182–6197 (2011) (with supp mat)
• Guest W, Cashman NR, Plotkin SS, “A Theory for the Anisotropic and Inhomogeneous Dielectric Properties of Proteins” Phys. Chem. Chem. Phys., 13 (13), 6286 – 6295 (2011)
• Linhananta A, Hadizadeh S, Plotkin SS, “An Effective Solvent Theory Connecting the Underlying Mechanisms of Osmolytes and Denaturants for Protein Stability” Biophys J.100, 459–468 (2011) Supplemental material is here.
• Guest W, Plotkin SS, Cashman NR, “Toward A Mechanism of Prion Misfolding and Structural Models of PrPSc: Current Knowledge and Future Directions“, J Toxicol Env Health Part A, 74:154–160 (2011)
• Guest W, Cashman NR, Plotkin SS, “Electrostatics in the Stability and Misfolding of the Prion Protein: Salt Bridges, Self-Energy, and Solvation” Biochem. Cell Biol 88, 371–381 (2010) Supplementary material is here.
• Morriss-Andrews A, Rottler J, Plotkin SS, “A Systematically Coarse-grained Model for DNA, and its Predictions for Persistence Length, Stacking, Twist, and Chirality” J Chem Phys 132, 035105 (2010) Supplementary material is here.
• Abrahamsson E, Plotkin SS, ”BioVEC: A Program for Biomolecule Visualization with Ellipsoidal Coarse-graining” J. Mol. Graph. Mod. 28, 140-145 (2009) [Supplementary Video]
• Mohazab AR, Plotkin SS, “Structural Alignment using the Generalized Euclidean Distance Between Conformations” Int. J. Quant. Chem. 109, 3217–3228 (2009)
• Li L, Guest W, Huang A, Plotkin SS, Cashman N, “Immunological Mimicry of PrPc-PrPSc Interactions: Antibody-Induced PrP Misfolding” Protein Engineering, Design and Selection 22(8):523-529 (2009)
• Mohazab AR, Plotkin SS, “Minimal Folding Pathways for Coarse-grained Biopolymer Fragments” Biophys J, 95 (12) 5496 (2008)
• Mohazab AR, Plotkin SS, “Minimal Distance Transformations Between Links and Polymers: Principles and Applications” J. Phys Condens Mat 20 (24) 244133 (2008)
• Plotkin SS, “Generalization of Distance to Higher Dimensional Objects” Proc. Natl. Acad. Sci. 104, 14899 (2007)
• Plotkin SS, “Determination of Barrier Heights and Prefactors from Protein Folding Rate Data“ Biophys J. 88, (6) (2005)
• Oztop B, Ejtehadi MR, Plotkin SS, “Protein Folding Rates Correlate with Heterogeneity of Folding Mechanism” Phys. Rev. Lett. 93, 208105 (2004) (Experimental references)
• Ejtehadi MR, Avall SP, Plotkin SS, “Three-body Interactions Improve the Prediction of Rate and Mechanism in Protein Folding Models” Proc. Natl. Acad. Sci. 101, 15088-15093 (2004)
• Clementi C, Plotkin SS, “The Effects of Non-native Interactions on Protein Folding Rates: Theory and Simulation” Prot. Sci. 13, 1750-1765 (2004)The appendices to this paper were converted into electronic supplementary material for some reason. Unfortunately 2 figures were lost during this conversion. Here they are: figure 11 and figure 12
• Plotkin SS, Wolynes PG, “Buffed Energy Landscapes: Another Solution to the Kinetic Paradoxes of Protein Folding” Proc. Natl. Acad. Sci. 100, (8) 4417-4422 (2003)
• Plotkin SS, Onuchic JN, “Understanding Protein Folding with Energy Landscape Theory II: Quantitative Aspects” Quart. Rev. Biophys. 35, 205-286 (2002)
• Plotkin SS, Onuchic JN, “Understanding Protein Folding with Energy Landscape Theory, Part I: Basic Concepts” Quart. Rev. Biophys. 35, 111-167 (2002)
• Plotkin SS, Onuchic JN, “Structural and Energetic Heterogeneity in Protein Folding I: Theory” J. Chem. Phys. 116 (12), 5263-5283 (2002)
• Plotkin SS, “Speeding Protein Folding Beyond the Go Model: How a Little Frustration Sometimes Helps” Proteins: Structure, Function, Genetics 45 (4), 337-345 (2001)
• Plotkin SS, Onuchic JN, “Investigation of Routes and Funnels in Protein Folding by Free Energy Functional Methods” Proc Natl Acad Sci 97 (12): 6509-6514 (2000)
• Plotkin SS, Wolynes PG, “Non-Markovian Configurational Diffusion and Reaction Coordinates for Protein Folding” Phys Rev Lett 80 (22): 5015-5018 (1998)
• Plotkin SS, Wang J, Wolynes PG, “Statistical Mechanics of Correlated Energy Landscape Models for Random Heteropolymers and Proteins” Physica D 107 (2-4): 322-325 (1997)
• Wang J, Plotkin SS, Wolynes PG “Configurational Diffusion on a Locally Connected Correlated Energy Landscape; Application to Finite, Random Heteropolymers” Journal De Physique I 7 (3): 395-421 (1997)
• Plotkin SS, Wang J, Wolynes PG, “Statistical Mechanics of a Correlated Energy Landscape Model for Protein Folding Funnels” J Chem Phys 106 (7): 2932-2948 (1997)
• Plotkin SS, Wang J, Wolynes PG, “Correlated Energy Landscape Model for Finite, Random Heteropolymers” Phys Rev E 53 (6): 6271-6296 Part B (1996)

Patents:

• Conserved Epitopes in Coronaviruses and Vaccines and Antibodies Thereto. US Patent No.: PCT/CA2024/050214 Evolutionarily conserved epitopes in beta-coronaviruses and vaccines and antibodies thereto. Inventors: Steven S Plotkin, Pranav Garg, Ching-Chung Hsueh, Santanu Sasidharan. Filed February 21, 2024
• “Antibodies Targeting Rack1 and Methods of Use Thereof” US Provisional Patent Application No. 63/438,178, Inventors: Neil R Cashman, Steven S Plotkin, Ching-Chung Hsueh, Beibei Zhao, Filed Jan 2023
• “Immunogens Targeting Oligomeric Tau and Methods of Generation and Use Thereof” Provisional Patent P69765US00, Filed Dec 2022
• “Chimeric Antibodies and Uses Thereof for Treating Coronavirus Infections” US Provisional Patent Application No. 63/053,405, Inventors: Steven S Plotkin, Ching-Chung Hsueh, Filed July 2020
• “Conformation-specific Epitopes in Tau, Antibodies Thereto and Methods Related Thereof” Provision Patent Application No. 62/853,121, Inventors: Steven S Plotkin, Neil R Cashman, Johanne Kaplan, Filed May 2020
• “Assays and Compositions for Seriological Detection of Sars-Cov-2” US Provisional Patent #63/027,332, Inventors: Neil R Cashman, Steven S Plotkin, Ebrima Gibbs, Adekunle Aina, Ching-Chung Hsueh, Filed May 2020
• “Epitopes in the First RNA Recognition Motif 1 (RRM1) of TDP-43 and Misfolding-Selective Antibodies Thereto” US Patent Application: No. 16/616,832, National Phase Entry of PCT/CA2018/050634, Inventors: Steven S Plotkin, Neil R Cashman, Xubiao Peng, Filed: Nov 25, 2019
• “Conformation-specific Epitopes in Alpha-synuclein, Antibodies Thereto and Methods Related Thereof” US Provisional Patent #62/820,701, Inventors: Neil R Cashman, Steven S. Plotkin, Xubiao Peng, Johanne Kaplan, Filed Oct 16, 2019
• “Methods and Systems for Predicting Mifolded Protein Epitopes ” US Patent 10,475,525, Inventors: Neil R Cashman, Steven S Plotkin, Will C Guest, Status: Granted, Issue date: November 12, 2019
• “Antibodies for Alpha-Synuclein” US Provisional Application No. 62/864,060, Inventors: Neil R Cashman, Steven S Plotkin, Xubiao Peng, Status: Filed, Date: June 20, 2019
• “Epitopes in amyloid beta and conformationally-selective antibodies thereto” Inventors: Steven S Plotkin and Neil R Cashman, Provisional Patent 62/393,615 Filed Sept 14, 2016
• “Epitopes in Amyloid beta and conformationally-selective antibodies thereto” Inventors: Steven S Plotkin and Neil R Cashman, Provisional Patent 62/365,634. Filed July 22, 2016
• “C-terminal epitopes in Amyloid beta and conformationally-selective antibodies thereto” Inventors: Steven S Plotkin and Neil R Cashman, Provisional Patent 62/352,346. Filed June 20, 2016
• “N-terminal epitopes in Amyloid beta and conformationally-selective antibodies thereto” Inventors: Steven S Plotkin and Neil R Cashman, Provisional Patent # 62/331,925, Filed May 11, 2016
• “Epitopes in Amyloid beta and antibodies thereto” Inventors: Steven S Plotkin and Neil R Cashman, Provisional Patent # 62/309,765, Filed March 17, 2016
• “Amyloid beta epitopes and antibodies thereto” Inventors: Steven S Plotkin and Neil R Cashman, Provisional Patent # 62/289893, Filing date: Filed February 1, 2016
• “Systems and Methods for Predicting Misfolded Protein Epitopes by Collective Coordinate Biasing” Inventor: Steven S Plotkin, Provisional Patent Application # 62/253044, Filed November 9, 2015
• “Methods and Systems for Determining Localized Dielectric Properties of a Molecule” Inventors: William C Guest, Neil R Cashman, Steven S Plotkin, Application #: 12/952,140  Publication #: US 2011/0125478 A1, Patent Filing date: Nov 22, 2010, Pub. Date: May 26, 2011
• “Methods and Systems for Predicting Misfolded Protein Epitopes” Inventors: Neil R Cashman, Steven S Plotkin, William C Guest, Application #: 12/574,637, Publication #: US 2010/0233176 A1, Patent Filing date: Oct 6, 2009, Pub. Date: Sep. 16, 2010