Zachary Levine, PhD
Assistant Professor AdjunctCards
About
Titles
Assistant Professor Adjunct
Biography
Zachary Levine is an Assistant Professor Adjunct of Pathology at Yale School of Medicine. While trained in computational biophysics with special emphasis in protein folding, his interests have recently expanded into solution biophysics measurements of soluble amyloid oligomers. Many of his projects combine atomistic molecular dynamics (MD) simulations with single-molecule fluorescence techniques (smFRET, FCS, and anisotropy) in order to deduce the physical and thermodynamic determinants of age-related diseases.
Appointments
Pathology
Assistant Professor AdjunctPrimary
Other Departments & Organizations
Education & Training
- Postdoctoral Training
- University of California Santa Barbara (2017)
- PhD
- University of Southern California, Physics (2013)
- MSc
- University of Southern California, Computer Science (2012)
- MA
- University of Southern California, Physics (2008)
- BS
- San Francisco State University, Physics (2006)
Research
Publications
2025
Drugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention
Bogin B, Levine Z. Drugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention. Journal Of Chemical Theory And Computation 2025, 21: 3204-3215. PMID: 40029731, DOI: 10.1021/acs.jctc.4c01160.Peer-Reviewed Original ResearchConceptsIslet amyloid polypeptideIntrinsically disordered proteinsConformational selectionDisordered proteinsHuman islet amyloid polypeptideMolecular dynamics simulationsStable binding sitesSelf-assembling sequencesIAPP sequenceFixed conformationAmyloid polypeptideUmbrella samplingBinding preferencesConformational specificityTwo-state modelDynamics simulationsConformational heterogeneityNew conformationsBinding sitesMolecular binding mechanismsConformationBinding mechanismFoldamersStructural conformationProteinBPS2025 - Decoupling the role of DNA on mutant p53 aggregation
Steinsaltz M, Levine Z. BPS2025 - Decoupling the role of DNA on mutant p53 aggregation. Biophysical Journal 2025, 124: 410a. DOI: 10.1016/j.bpj.2024.11.2206.Peer-Reviewed Original ResearchBPS2025 - Decoupling the role of DNA on mutant p53 aggregation
Steinsaltz M, Levine Z. BPS2025 - Decoupling the role of DNA on mutant p53 aggregation. Biophysical Journal 2025, 124: 512a. DOI: 10.1016/j.bpj.2024.11.2691.Peer-Reviewed Original ResearchBPS2025 - Concentration-dependent role of apolipoprotein E in amyloid beta clearance by human astrocytes
Nurmakova K, Levine Z. BPS2025 - Concentration-dependent role of apolipoprotein E in amyloid beta clearance by human astrocytes. Biophysical Journal 2025, 124: 407a-408a. DOI: 10.1016/j.bpj.2024.11.2193.Peer-Reviewed Original Research
2024
Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology
Miller B, Kim S, Cao K, Mehta H, Thumaty N, Kumagai H, Iida T, McGill C, Pike C, Nurmakova K, Levine Z, Sullivan P, Yen K, Ertekin‐Taner N, Atzmon G, Barzilai N, Cohen P. Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology. Aging Cell 2024, 23: e14153. PMID: 38520065, PMCID: PMC11258485, DOI: 10.1111/acel.14153.Peer-Reviewed Original ResearchAPOE4 carriersAPOE4 alleleAmyloid beta clearanceMouse model of amyloidosisAlzheimer's diseaseAmyloid-beta pathologyIn silico analysisAmyloid-beta accumulationMitochondrial-derived peptideGenes associated with phagocytosisResistance to ADModel of amyloidosisAmyloid-betaBeta pathologyAssociated with longevitySilico analysisHumaninFactors to Alzheimer's diseaseApoE4Transcriptomic assessmentAmino acidsInfluence longevityAllelesPhagocytosisAshkenazi descentDecoupling sequence and conformational determinants of strong IDP binders to inform therapeutic intervention
Bogin B, Levine Z. Decoupling sequence and conformational determinants of strong IDP binders to inform therapeutic intervention. Biophysical Journal 2024, 123: 74a. DOI: 10.1016/j.bpj.2023.11.520.Peer-Reviewed Original Research
2023
Apolipoprotein E polymorphism‐dependent effects on cellular function
Beyer B, Levine Z. Apolipoprotein E polymorphism‐dependent effects on cellular function. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.077424.Peer-Reviewed Original ResearchApolipoprotein EStructure:function relationshipsCombination of cell-basedIsogenic hiPSC linesTransport of lipidsSubcellular localizationE4 isoformCellular functionsFunction of apolipoprotein EBiophysical approachesLiving cellsTransport of E2Cell typesCo-localizationCentral nervous systemLipoprotein particlesIsoformsHuman astrocytesRelationship of apolipoprotein EHiPSC linesCell-basedInvestigate mechanismsApolipoproteinCellsOrganellesComparing the structure and stability of diverse amyloid beta oligomers using fluorescence correlation spectroscopy
Nurmakova K, Levine Z. Comparing the structure and stability of diverse amyloid beta oligomers using fluorescence correlation spectroscopy. Biophysical Journal 2023, 122: 350a. DOI: 10.1016/j.bpj.2022.11.1944.Peer-Reviewed Original Research
2019
The Mitochondrial Peptide Humanin Targets but Does Not Denature Amyloid Oligomers in Type II Diabetes
Levine ZA, Teranishi K, Okada AK, Langen R, Shea JE. The Mitochondrial Peptide Humanin Targets but Does Not Denature Amyloid Oligomers in Type II Diabetes. Journal Of The American Chemical Society 2019, 141: 14168-14179. PMID: 31456396, DOI: 10.1021/jacs.9b04995.Peer-Reviewed Original Research
2018
A threonine zipper that mediates protein–protein interactions: Structure and prediction
Oi C, Treado JD, Levine ZA, Lim CS, Knecht KM, Xiong Y, O'Hern CS, Regan L. A threonine zipper that mediates protein–protein interactions: Structure and prediction. Protein Science 2018, 27: 1969-1977. PMID: 30198622, PMCID: PMC6201716, DOI: 10.1002/pro.3505.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsProtein-protein interfacesZipper structureBeta-barrel proteinsIntermonomer hydrogen bondsBarrel proteinsThr residueSide-chain dihedral anglesBiotechnological applicationsProtein interfacesMolecular dynamics simulationsDihedral angleSide-chain conformationsThrH-bondingHydrogen bondsChain conformationMD simulationsSteric constraintsDrug discoveryDynamics simulationsResidues
Academic Achievements & Community Involvement
News & Links
Media
- Cover art from our lab was featured in the Sept. 11th, 2019 issue of the Journal of the American Chemical Society (JACS). "The small, mitochondrial peptide humanin binds to amyloid oligomers in Type II Diabetes, acting as an endogenous amyloid chaperone that regulates fibril growth. Outside of their native environments, mitochondrial peptides exhibit a remarkable potential for targeting intermediate protein oligomers in the cytosol and inhibiting cytotoxicity across multiple amyloid diseases."
News
Get In Touch
Contacts
Mailing Address
Yale University
266 Whitney Ave., Bass Center, Rm. 320
New Haven, CT 06520-8114
United States
Locations
Bass Center
Lab
266 Whitney Avenue, Rm 320
New Haven, CT 06511