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
Disease Teams:
Institute for CyberScience (ICS) - Co-hire
Research Interests
- Proteins
- Ribosomes
- Protein Folding
- Kinetics
- Codon
- Peptides
- Messenger RNA
- Amino Acids
- Static Electricity
- Proteome
- Molecular Models
- Temperature
Recent Publications
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
2019
Sharma, AK, Sormanni, P, Ahmed, N, Ciryam, P, Friedrich, UA, Kramer, G & O'Brien, EP 2019, 'A chemical kinetic basis for measuring translation initiation and elongation rates from ribosome profiling data', PLoS computational biology, vol. 15, no. 5, e1007070. https://doi.org/10.1371/journal.pcbi.1007070
Leininger, SE, Trovato, F, Nissley, DA & O’Brien, EP 2019, 'Domain topology, stability, and translation speed determine mechanical force generation on the ribosome', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 12, pp. 5523-5532. https://doi.org/10.1073/pnas.1813003116
Ahmed, N, Sormanni, P, Ciryam, P, Vendruscolo, M, Dobson, CM & O’Brien, EP 2019, 'Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming', Scientific reports, vol. 9, no. 1, 6256. https://doi.org/10.1038/s41598-019-42348-x
Leininger, SE, Narayan, K, Deutsch, C & O'Brien, EP 2019, 'Mechanochemistry in Translation', Biochemistry, vol. 58, no. 47, pp. 4657-4666. https://doi.org/10.1021/acs.biochem.9b00260