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Edward P. O'Brien, Jr., PhD

Edward P. O'Brien, Jr., PhD

Professor, Chemistry
Scientific Program:Mechanisms of Carcinogenesis
Disease Teams:
Institute for CyberScience (ICS) - Co-hire
EPO2@psu.edu

Research Interests

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  • Proteins
  • Ribosomes
  • Protein Folding
  • Kinetics
  • Codon
  • Peptides
  • Messenger RNA
  • Amino Acids
  • Static Electricity
  • Proteome
  • Molecular Models
  • Temperature
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Recent Publications

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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, 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

2021

Sharma, AK, Venezian, J, Shiber, A, Kramer, G, Bukau, B & O’Brien, EP 2021, 'Combinations of slow-translating codon clusters can increase mRNA half-life in Saccharomyces cerevisiae', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 51, e2026362118. https://doi.org/10.1073/pnas.2026362118
Nguyen, H, Lan, PD, Nissley, DA, O'Brien, EP & Li, MS 2021, 'Electrostatic Interactions Explain the Higher Binding Affinity of the CR3022 Antibody for SARS-CoV-2 than the 4A8 Antibody', Journal of Physical Chemistry B, vol. 125, no. 27, pp. 7368-7379. https://doi.org/10.1021/acs.jpcb.1c03639
Inam, H, Sokirniy, I, Rao, Y, Shah, A, Naeemikia, F, O'Brien, E, Dong, C, McCandlish, DM & Pritchard, JR 2021, 'Genomic and experimental evidence that ALKATI does not predict single agent sensitivity to ALK inhibitors', iScience, vol. 24, no. 11, 103343. https://doi.org/10.1016/j.isci.2021.103343
Jiang, Y & O’Brien, EP 2021, 'Mechanical Forces Have a Range of Effects on the Rate of Ribosome Catalyzed Peptidyl Transfer Depending on Direction', Journal of Physical Chemistry B, vol. 125, no. 26, pp. 7128-7136. https://doi.org/10.1021/acs.jpcb.1c02263
Shao, D, Ahmed, N, Soni, N & O’Brien, EP 2021, 'RiboA: a web application to identify ribosome A-site locations in ribosome profiling data', BMC bioinformatics, vol. 22, no. 1, 156. https://doi.org/10.1186/s12859-021-04068-w
Leininger, SE, Rodriguez, J, Vu, QV, Jiang, Y, Li, MS, Deutsch, C & O'Brien, EP 2021, 'Ribosome Elongation Kinetics of Consecutively Charged Residues Are Coupled to Electrostatic Force', Biochemistry, vol. 60, no. 43, pp. 3223-3235. https://doi.org/10.1021/acs.biochem.1c00507
Vu, QV, Jiang, Y, Li, MS & O'Brien, EP 2021, 'The driving force for co-translational protein folding is weaker in the ribosome vestibule due to greater water ordering', Chemical Science, vol. 12, no. 35, pp. 11851-11857. https://doi.org/10.1039/d1sc01008e

2020

Nguyen, HL, Lan, PD, Thai, NQ, Nissley, DA, O'Brien, EP & Li, MS 2020, 'Does SARS-CoV-2 bind to human ACE2 more strongly than does SARS-CoV?', Journal of Physical Chemistry B, vol. 124, no. 34, pp. 7336-7347. https://doi.org/10.1021/acs.jpcb.0c04511
Nissley, DA, Vu, QV, Trovato, F, Ahmed, N, Jiang, Y, Li, MS & O'Brien, EP 2020, 'Electrostatic Interactions Govern Extreme Nascent Protein Ejection Times from Ribosomes and Can Delay Ribosome Recycling', Journal of the American Chemical Society, vol. 142, no. 13, pp. 6103-6110. https://doi.org/10.1021/jacs.9b12264
Leininger, SE, Deutsch, C & O’Brien, EP 2020, 'Forcing the ribosome to change its message', Journal of Biological Chemistry, vol. 295, no. 20, pp. 6809-6810. https://doi.org/10.1074/jbc.H120.013747
Wolfe, DK, Persichetti, JR, Sharma, AK, Hudson, PS, Woodcock, HL & O'brien, EP 2020, 'Hierarchical Markov State Model Building to Describe Molecular Processes', Journal of Chemical Theory and Computation, vol. 16, no. 3, pp. 1816-1826. https://doi.org/10.1021/acs.jctc.9b00955
Ahmed, N, Friedrich, UA, Sormanni, P, Ciryam, P, Altman, NS, Bukau, B, Kramer, G & O'Brien, EP 2020, 'Pairs of amino acids at the P- and A-sites of the ribosome predictably and causally modulate translation-elongation rates: Amino acid pairs module translation-elongation rates', Journal of Molecular Biology, vol. 432, no. 24, 166696. https://doi.org/10.1016/j.jmb.2020.10.030
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