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Researcher Profile

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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

Research Interests

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

Recent Publications


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.
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.
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.
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.


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.
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.
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.


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.
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.
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.
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.
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.
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.


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.
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.
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.
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.
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.
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.
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.


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.
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.
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.
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.
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.