Edward O'Brien

Professional Appointments and Affiliations

Professor of Chemistry and of the Institute for Computational and Data Sciences

Director of the NSF National Synthesis Center for Emergence in the Molecular and Cellular Sciences

Education

Post-doc, University of Cambridge, 2013

Ph.D. Chemical Physics, University of Maryland College Park, 2008

B.S. Biochemistry, University of the Sciences, 2002

Honors and Awards

Inaugural Discovery Cohort - Awarded by the National Academy of Science. (2026) 

Elected Co-Chair of Gordon Research Conference “Protein Folding Dynamics” 

Kavli Fellow – Awarded by the National Academy of Science. (2023) 

Presidential Early Career Award in Science and Engineering (2019)

American Chemical Society OpenEye Outstanding Junior Faculty Award in Computational Chemistry (2018)

Priestly Undergraduate Teaching Award (2016)

National Science Foundation - Deutsche Forschungsgemeinschaft CAREER Supplement (2016-2019)

National Science Foundation CAREER Award (2016-2021)

Elected Program Chair, 60th Biophysical Society National Meeting, "Biopolymers In Vivo" subgroup (2016)

Human Frontier's Science Program Grant Recipient (2015-2018)

Biotechnology and Biology Sciences Research Council (UK) David Phillips Fellowship (2013) – Declined

The Royal Society (UK) University Research Fellowship (2013) – Declined

Engineering and Physical Sciences Research Council (UK) Grant recipient (2012-2013)

National Science Foundation Postdoctoral Fellow (2009-2012)

National Science Foundation EAPSI Fellow (2007)

National Institutes of Health GPP Biophysics Fellow (2003-2008)

Selected Publications

Y. Jiang, A. Jain, S. Ghaemmaghami, and E. P. O’Brien* “Protein entanglement misfolding determines divergent fates: proteasomal degradation or persistence in near-native misfolded states” 2026.  bioRxiv https://doi.org/10.64898/2026.04.15.718748

Q. V. Vu, I. Sitarik, D. A. Nissley, and E. P. O’Brien* “Native entanglement misfolding contributes to age-associated structural changes across the Saccharomyces cerevisiae proteome” 2026. bioRxiv https://doi.org/10.64898/2026.04.15.717356

M. F. Anglero Mendez, I. Sitarik, Q. V. Vu, P. Totoo, J. D. Stephenson, H. Song, and E. P. O’Brien* “Natively entangled proteins are linked to human disease and pathogenic mutations likely due to a greater misfolding propensity” 2026. bioRxiv https://doi.org/10.64898/2026.04.15.718104

I. Sitarik, Y. Jiang, H. Song, and E. P. O’Brien* “Detecting misfolded non-covalent lasso entanglements in protein structures, simulation trajectories, and mass spectrometry data” 2026. bioRxiv https://doi.org/10.64898/2026.04.15.718775

Y. Jiang, Y. Xia, I. Sitarik, P. Sharma, H. Song, S. D. Fried and E. P. O’Brien* “Protein misfolding involving entanglements provides a structural explanation for the origin of stretched-exponential refolding kinetics” Sci. Adv. 2025, 11. eads7379

Q. V. Vu, I. Sitarik, Y. Jiang, Y. Xia, P. Sharma, D. Yadav, H. Song, M. S. Li and E. P. O’Brien* “Non-native entanglement protein misfolding observed in all-atom simulations and supported by experimental structural ensembles” Sci. Adv. 2025, 11. eadt8974

I. Sitarik, Q. Vu, J. Petucci, P. Frutos, H. Song and E. P. O’Brien* “A widespread protein misfolding mechanism is differentially rescued in vitro by chaperones based on gene essentiality” Nat. Commun. 2025, 16. 10870

Q. V. Vu, I. Sitarik, M. S. Li and E. P. O’Brien* “Noncovalent lasso entanglements are common in experimentally derived intrinsically disordered protein ensembles and strongly influenced by protein length and charge” J. Phys. Chem. B 2025, 129. 4682-4691

R. Halder, D. Nissley, I. Sitarik, Y. Jiang, Y. Rao, Q. Vu, M. S. Li, J. Pritchard and E. P. O’Brien* “How soluble misfolded proteins bypass chaperones at the molecular level” Nat. Commun., 2023, 14. 3689. 

Y. Jiang, S. Neti, I. Sitarik, P. Pradhyan, P. To, Y. Xia, S.D. Fried, S. Booker and E. P. O’Brien* “How synonymous mutations alter enzyme structure and function over long time scales” Nat. Chem. 2023, 15. 308-318. 
Highlighted in Nature Reviews Microbiology Altmetric score of 271: top 1% of papers of similar age from all journals.

D. Nissley, I. Sitarik, F. Travato, Q. Vu, M. S. Li and E. P. O’Brien* “Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and non-functional” Nat. Commun. 2022, 13. 3081.

Q. Vu, Y. Jiang, M. S. Li and E. P. O’Brien* “The driving force for co-translational protein folding is weaker near the ribosome surface due to greater water ordering.” Chem. Sci., 2021, 12. 11851-11857.

A. K. Sharma, A. Schiber, B. Bukau, G. Kramer and E. P. O’Brien* “Combinations of slow translating codon clusters can increase mRNA half-life in S. cerevisiae.” Proc. Natl. Acad. Sci., 2021. 118, e2026362118.

S. Leininger, J. Rodriguez; Q. Vu, Y. Jiang. M. S. Li, Ma, C. Deutsch and E. P. O’Brien* “Ribosome elongation kinetics are coupled to electrostatic force generation” Biochem., 2021, 60. 3223-3235.