Edward P. O'Brien, Jr., PhD - Penn State Cancer Institute
Researcher Profile
Edward P. O'Brien, Jr., PhD
Professor, Chemistry
Scientific Program:Mechanisms of Carcinogenesis
Recent Publications
2025
Sitarik, I, Vu, QV, Petucci, J, Frutos, P, Song, H & O’Brien, EP 2025, 'A widespread protein misfolding mechanism is differentially rescued in vitro by chaperones based on gene essentiality', Nature communications, vol. 16, no. 1, 10870. https://doi.org/10.1038/s41467-025-66236-3
Lentzsch, AM, Fan, Z, Irshad, IU, O’Brien, EP, Sharma, AK, Green, R & Shan, SO 2025, 'HYPK promotes N-terminal protein acetylation through rapid ribosome exchange of NatA', Molecular cell, vol. 85, no. 24, pp. 4562-4574.e6. https://doi.org/10.1016/j.molcel.2025.11.017
Vu, QV, Sitarik, I, Jiang, Y, Xia, Y, Sharma, P, Yadav, D, Song, H, Li, MS, Fried, SD & O'Brien, EP 2025, 'Non-native entanglement protein misfolding observed in all-atom simulations and supported by experimental structural ensembles', Science Advances, vol. 11, no. 32, eadt8974, pp. 1-11. https://doi.org/10.1126/sciadv.adt8974
Vu, QV, Sitarik, I, Li, MS & O’Brien, EP 2025, 'Noncovalent Lasso Entanglements are Common in Experimentally Derived Intrinsically Disordered Protein Ensembles and Strongly Influenced by Protein Length and Charge', Journal of Physical Chemistry B, vol. 129, no. 19, pp. 4682-4691. https://doi.org/10.1021/acs.jpcb.5c01260
Petucci, J, Sitarik, I, Jiang, Y, Rana, V, Song, H & O'Brien, EP 2025, 'Properties Governing Native State Entanglements and Relationships to Protein Function', Journal of Molecular Biology, vol. 437, no. 19, 169342. https://doi.org/10.1016/j.jmb.2025.169342
Jiang, Y, Xia, Y, Sitarik, I, Sharma, P, Song, H, Fried, SD & O’Brien, EP 2025, 'Protein misfolding involving entanglements provides a structural explanation for the origin of stretched-exponential refolding kinetics', Science Advances, vol. 11, no. 11, eads7379. https://doi.org/10.1126/sciadv.ads7379
Galmozzi, CV, Tippmann, F, Wruck, F, Auburger, JJ, Kats, I, Guennigmann, M, Till, K, O´brien, EP, Tans, SJ, Kramer, G & Bukau, B 2025, 'Proteome-wide determinants of co-translational chaperone binding in bacteria', Nature communications, vol. 16, no. 1, 4361. https://doi.org/10.1038/S41467-025-59067-9
2024
Lan, PD, Nissley, DA, O’Brien, EP, Nguyen, TT & Li, MS 2024, 'Deciphering the free energy landscapes of SARS-CoV-2 wild type and Omicron variant interacting with human ACE2', Journal of Chemical Physics, vol. 160, no. 5, 055101. https://doi.org/10.1063/5.0188053
Jiang, Y, Deane, CM, Morris, GM & O’Brien, EP 2024, 'It is theoretically possible to avoid misfolding into non-covalent lasso entanglements using small molecule drugs', PLoS computational biology, vol. 20, no. 3 March, e1011901. https://doi.org/10.1371/journal.pcbi.1011901
Rana, V, Sitarik, I, Petucci, J, Jiang, Y, Song, H & O'Brien, EP 2024, 'Non-covalent Lasso Entanglements in Folded Proteins: Prevalence, Functional Implications, and Evolutionary Significance', Journal of Molecular Biology, vol. 436, no. 6, 168459. https://doi.org/10.1016/j.jmb.2024.168459
Lan, PD, O’Brien, EP & Li, MS 2024, 'Pulling Forces Differentially Affect Refolding Pathways Due to Entangled Misfolded States in SARS-CoV-1 and SARS-CoV-2 Receptor Binding Domain', Biomolecules, vol. 14, no. 10, 1327. https://doi.org/10.3390/biom14101327
Lan, PD, Nissley, DA, Sitarik, I, Vu, QV, Jiang, Y, To, P, Xia, Y, Fried, SD, Li, MS & O'Brien, EP 2024, 'Synonymous Mutations Can Alter Protein Dimerization Through Localized Interface Misfolding Involving Self-entanglements', Journal of Molecular Biology, vol. 436, no. 6, 168487. https://doi.org/10.1016/j.jmb.2024.168487
2023
Halder, R, Nissley, DA, Sitarik, I, Jiang, Y, Rao, Y, Vu, QV, Li, MS, Pritchard, J & O’Brien, EP 2023, 'How soluble misfolded proteins bypass chaperones at the molecular level', Nature communications, vol. 14, no. 1, 3689. https://doi.org/10.1038/s41467-023-38962-z
Rao, Y, Ahmed, N, Pritchard, J & O’Brien, EP 2023, 'Incorporating mutational heterogeneity to identify genes that are enriched for synonymous mutations in cancer', BMC bioinformatics, vol. 24, no. 1, 462. https://doi.org/10.1186/s12859-023-05521-8
Vu, QV, Nissley, DA, Jiang, Y, O’Brien, EP & Li, MS 2023, 'Is Posttranslational Folding More Efficient Than Refolding from a Denatured State: A Computational Study', Journal of Physical Chemistry B, vol. 127, no. 21, pp. 4761-4774. https://doi.org/10.1021/acs.jpcb.3c01694
2022
Zhao, B, Rao, Y, Leighow, S, O’Brien, EP, Gilbert, L & Pritchard, JR 2022, 'A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments', Nature communications, vol. 13, no. 1, 625. https://doi.org/10.1038/s41467-022-28045-w
Nguyen, H, Lan, PD, Nissley, DA, O'Brien, EP & Li, MS 2022, 'Cocktail of REGN Antibodies Binds More Strongly to SARS-CoV-2 Than Its Components, but the Omicron Variant Reduces Its Neutralizing Ability', Journal of Physical Chemistry B, vol. 126, no. 15, pp. 2812-2823. https://doi.org/10.1021/acs.jpcb.2c00708
Jiang, Y, Neti, SS, Sitarik, I, Pradhan, P, To, P, Xia, Y, Fried, SD, Booker, SJ & O’Brien, EP 2023, 'How synonymous mutations alter enzyme structure and function over long timescales', Nature Chemistry, vol. 15, no. 3, pp. 308-318. https://doi.org/10.1038/s41557-022-01091-z
Persichetti, JR, Jiang, Y, Hudson, PS & O'Brien, EP 2022, 'Modeling Ensembles of Enzyme Reaction Pathways with Hi-MSM Reveals the Importance of Accounting for Pathway Diversity', Journal of Physical Chemistry B, vol. 126, no. 47, pp. 9748-9758. https://doi.org/10.1021/acs.jpcb.2c04496
Zhu, M, Kuechler, ER, Wong, RWK, Calabrese, G, Sitarik, IM, Rana, V, Stoynov, N, O'Brien, EP, Gsponer, J & Mayor, T 2022, 'Pulse labeling reveals the tail end of protein folding by proteome profiling', Cell Reports, vol. 40, no. 3, 111096. https://doi.org/10.1016/j.celrep.2022.111096
Nissley, DA, Jiang, Y, Trovato, F, Sitarik, I, Narayan, KB, To, P, Xia, Y, Fried, SD & O’Brien, EP 2022, 'Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and less functional', Nature communications, vol. 13, no. 1, 3081. https://doi.org/10.1038/s41467-022-30548-5