Steven S. Plotkin
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View article: Protein misfolding‐specific epitope identification for passive and active immunotherapy of neurodegenerative diseases
Protein misfolding‐specific epitope identification for passive and active immunotherapy of neurodegenerative diseases Open
Background Toxic misfolded proteins underlie the pathogenesis of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease (AD&PD), and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). Generation of therapeutic…
View article: Relationship between efficacy and preferential targeting of soluble Aβ aggregates
Relationship between efficacy and preferential targeting of soluble Aβ aggregates Open
INTRODUCTION Amyloid beta (Aβ)‐directed antibodies have shown varying degrees of efficacy against Alzheimer's disease (AD). This study explored the relationship between targeting of Aβ molecular species and therapeutic efficacy/adverse eff…
View article: Reproductive success of inbred strain MV31 of the ctenophore<i>Mnemiopsis leidyi</i>in a self-sustaining inland laboratory culture system
Reproductive success of inbred strain MV31 of the ctenophore<i>Mnemiopsis leidyi</i>in a self-sustaining inland laboratory culture system Open
Ctenophores are an attractive lineage for studying animal evolution due to their early divergence from other metazoans. Among Ctenophora, Mnemiopsis leidyi is a model system for developmental, cellular, molecular genetic, and evolutionary …
View article: Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells
Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells Open
Mutations in the protein superoxide dismutase-1 (SOD1) promote its misfolding and aggregation, ultimately causing familial forms of the debilitating neurodegenerative disease amyotrophic lateral sclerosis (ALS). Currently, over 220 (mostly…
View article: Selective targeting and protection against toxic amyloid‐beta oligomers by PMN310, a monoclonal antibody rationally designed for greater therapeutic potency in Alzheimer’s disease
Selective targeting and protection against toxic amyloid‐beta oligomers by PMN310, a monoclonal antibody rationally designed for greater therapeutic potency in Alzheimer’s disease Open
Background A large body of evidence indicates that the most pathogenic species of amyloid‐beta (Aß) in Alzheimer’s disease (AD) consists of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Clinical results to dat…
View article: Rational design of a vaccine for Alzheimer’s disease using a computationally‐derived conformational epitope to selectively target toxic amyloid‐beta oligomers
Rational design of a vaccine for Alzheimer’s disease using a computationally‐derived conformational epitope to selectively target toxic amyloid‐beta oligomers Open
Background Amyloid‐beta (Aß) vaccines have the potential to protect against disease but also carry the risk of eliciting proinflammatory T cell responses causing meningoencephalitis, and plaque‐reactive antibodies that can increase the ris…
View article: Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells
Amyloidogenic regions in beta-strands II and III modulate the aggregation and toxicity of SOD1 in living cells Open
Mutations in the protein superoxide dismutase-1 (SOD1) promote its misfolding and aggregation, ultimately causing familial forms of the debilitating neurodegenerative disease amyotrophic lateral sclerosis (ALS). Currently, over 220 (mostly…
View article: Molecular dynamics trajectories for "Reservoir-REMD facilitates kinetic rescue from metastable peptide conformations
Molecular dynamics trajectories for "Reservoir-REMD facilitates kinetic rescue from metastable peptide conformations Open
The molecular dynamics-generated ensemble dataset for cyclo-(cGHHQKLV), used in the manuscript "Reservoir-REMD facilitates kinetic rescue from metastable peptide conformations". The dataset consists of 14 + 6 =20 .dcd files, and one .pdb f…
View article: Molecular dynamics trajectories for "Reservoir-REMD facilitates kinetic rescue from metastable peptide conformations
Molecular dynamics trajectories for "Reservoir-REMD facilitates kinetic rescue from metastable peptide conformations Open
The molecular dynamics-generated ensemble dataset for cyclo-(cGHHQKLV), used in the manuscript "Reservoir-REMD facilitates kinetic rescue from metastable peptide conformations". The dataset consists of 14 + 6 =20 .dcd files, and one .pdb f…
View article: De novo design of a<i>β</i>-helix tau protein scaffold: An oligomer-selective vaccine immunogen candidate for Alzheimer’s disease
De novo design of a<i>β</i>-helix tau protein scaffold: An oligomer-selective vaccine immunogen candidate for Alzheimer’s disease Open
Tau pathology is associated with many neurodegenetive disorders, including Alzheimer’s disease (AD), where the spatio-temporal pattern of tau neurofibrillary tangles strongly correlates with disease progression, which motivates therapeutic…
View article: PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles
PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles Open
The comparison of protein conformational ensembles is of central importance in structural biology. However, there are few computational methods for ensemble comparison, and those that are readily available, such as ENCORE, utilize methods …
View article: Molecular dynamics-generated ensemble dataset of ubiquitin; for "PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles"
Molecular dynamics-generated ensemble dataset of ubiquitin; for "PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles" Open
The molecular dynamics-generated ensemble dataset (229Mb zip file) for ubiquitin, used in the manuscript "PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles", submitted to the Journal of Chemical In…
View article: Molecular dynamics-generated ensemble dataset of ubiquitin; for "PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles"
Molecular dynamics-generated ensemble dataset of ubiquitin; for "PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles" Open
The molecular dynamics-generated ensemble dataset (229Mb zip file) for ubiquitin, used in the manuscript "PROTHON: A Local Order Parameter-Based Method for Efficient Comparison of Protein Ensembles", submitted to the Journal of Chemical In…
View article: Predicting the feasibility of targeting a conserved region on the S2 domain of the SARS-CoV-2 spike protein
Predicting the feasibility of targeting a conserved region on the S2 domain of the SARS-CoV-2 spike protein Open
The efficacy of vaccines against the SARS-CoV-2 virus significantly declines with the emergence of mutant strains, prompting investigation into the feasibility of targeting highly conserved but often cryptic regions on the S2 domain of spi…
View article: Accelerated ensemble generation for cyclic peptides using a Reservoir-REMD implementation in GROMACS
Accelerated ensemble generation for cyclic peptides using a Reservoir-REMD implementation in GROMACS Open
Cyclic peptides naturally occur as antibiotics, fungicides, and immunosuppressants, and have been adapted for use as potential therapeutics. Scaffolded cyclic peptide antigens have many protein characteristics such as reduced toxicity, inc…
View article: Rational Generation of Monoclonal Antibodies Selective for Pathogenic Forms of Alpha-Synuclein
Rational Generation of Monoclonal Antibodies Selective for Pathogenic Forms of Alpha-Synuclein Open
Misfolded toxic forms of alpha-synuclein (α-Syn) have been implicated in the pathogenesis of synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). The α-Syn oligomers and…
View article: Optimizing Epitope Conformational Ensembles Using α-Synuclein Cyclic Peptide “Glycindel” Scaffolds: A Customized Immunogen Method for Generating Oligomer-Selective Antibodies for Parkinson’s Disease
Optimizing Epitope Conformational Ensembles Using α-Synuclein Cyclic Peptide “Glycindel” Scaffolds: A Customized Immunogen Method for Generating Oligomer-Selective Antibodies for Parkinson’s Disease Open
Effectively presenting epitopes on immunogens, in order to raise conformationally selective antibodies through active immunization, is a central problem in treating protein misfolding diseases, particularly neurodegenerative diseases such …
View article: First Principles Calculation of Protein–Protein Dimer Affinities of ALS-Associated SOD1 Mutants
First Principles Calculation of Protein–Protein Dimer Affinities of ALS-Associated SOD1 Mutants Open
Cu,Zn superoxide dismutase (SOD1) is a 32 kDa homodimer that converts toxic oxygen radicals in neurons to less harmful species. The dimerization of SOD1 is essential to the stability of the protein. Monomerization increases the likelihood …
View article: Optimizing epitope conformational ensembles using<i>α</i>-synuclein cyclic peptide “glycindel” scaffolds: A customized immunogen method for generating oligomer-selective antibodies for Parkinson’s disease
Optimizing epitope conformational ensembles using<i>α</i>-synuclein cyclic peptide “glycindel” scaffolds: A customized immunogen method for generating oligomer-selective antibodies for Parkinson’s disease Open
Effectively presenting epitopes on immunogens, in order to raise conformationally selective antibodies through active immunization, is a central problem in treating protein misfolding diseases, particularly neurodegenerative diseases such …
View article: A method for systematically ranking therapeutic drug candidates using multiple uncertain screening criteria
A method for systematically ranking therapeutic drug candidates using multiple uncertain screening criteria Open
Multiple different screening tests for candidate leads in drug development may often yield conflicting or ambiguous results, sometimes making the selection of leads a nontrivial maximum-likelihood ranking problem. Here, we employ methods f…
View article: Epitope prediction for oligomer‐selective antibodies in tau and Aβ
Epitope prediction for oligomer‐selective antibodies in tau and Aβ Open
Background Previous studies of Alzheimer’s disease (AD) pathology point to cytotoxic tau as a cause of neuronal cell death, which is induced or exacerbated by soluble misfolded Aβ oligomers. Soluble misfolded species of both tau and Aβ are…
View article: Rationally designed antibodies selective for pathogenic tau aggregates
Rationally designed antibodies selective for pathogenic tau aggregates Open
Background Tauopathies are neurodegenerative disorders characterized by the abnormal aggregation of tau protein in the brain. Soluble toxic tau aggregates have the ability to transfer from cell‐to‐cell and to induce newly formed aggregates…
View article: Tryptophan residues in TDP-43 and SOD1 mediate the cross-seeding and toxicity of SOD1
Tryptophan residues in TDP-43 and SOD1 mediate the cross-seeding and toxicity of SOD1 Open
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons. Neuronal superoxide dismutase-1 (SOD1) inclusion bodies are characteristic of familial ALS with SOD1 mutations, while a hallmark of sporadic ALS is …