Edward O’Brien

Professor of Chemistry

Edward O’Brien

Research Summary

Developing and applying Physical Bioinformatic techniques to measure rates of translation transcriptome-wide and their molecular origins as relates to fundamental biology and disease.

Huck Graduate Students

Huck Affiliations

Most Recent Publications

Protein misfolding involving entanglements provides a structural explanation for the origin of stretched-exponential refolding kinetics

Yang Jiang, Yingzi Xia, Ian Sitarik, Piyoosh Sharma, Hyebin Song, Stephen D. Fried, Edward P. O’Brien, 2025, Science advances

Pulling Forces Differentially Affect Refolding Pathways Due to Entangled Misfolded States in SARS-CoV-1 and SARS-CoV-2 Receptor Binding Domain

Pham Dang Lan, Edward P. O’Brien, Mai Suan Li, 2024, Biomolecules

Non-covalent Lasso Entanglements in Folded Proteins: Prevalence, Functional Implications, and Evolutionary Significance

Viraj Rana, Ian Sitarik, Justin Petucci, Yang Jiang, Hyebin Song, Edward P. O'Brien, 2024, Journal of Molecular Biology on p. 168459

Synonymous Mutations Can Alter Protein Dimerization Through Localized Interface Misfolding Involving Self-entanglements

Pham Lan, Daniel Nissley, Ian Sitarik, Quyen Vu, Yang Jiang, Philip To, Yingzi Xia, Stephen Fried, Mai Li, Edward P. O'Brien, 2024, Journal of Molecular Biology on p. 168487

It is theoretically possible to avoid misfolding into non-covalent lasso entanglements using small molecule drugs

Yang Jiang, Charlotte M. Deane, Garrett M. Morris, Edward P. O’Brien, 2024, PLoS Computational Biology

Deciphering the free energy landscapes of SARS-CoV-2 wild type and Omicron variant interacting with human ACE2

Pham Dang Lan, Daniel A. Nissley, Edward P. O’Brien, Toan T. Nguyen, Mai Suan Li, 2024, Journal of Chemical Physics

Incorporating mutational heterogeneity to identify genes that are enriched for synonymous mutations in cancer

Yiyun Rao, Nabeel Ahmed, Justin Pritchard, Edward P. O’Brien, 2023, BMC Bioinformatics

How soluble misfolded proteins bypass chaperones at the molecular level

Ritaban Halder, Daniel Nissley, Ian Sitarik, Yang Jiang, Yiyun Rao, Quyen Vu, Mai Li, Justin Pritchard, Edward P. O’Brien, 2023, Nature Communications on p. 3689

Is Posttranslational Folding More Efficient Than Refolding from a Denatured State: A Computational Study

Quyen Vu, Daniel Nissley, Yang Jiang, Edward P. O’Brien, Mai Li, 2023, Journal of Physical Chemistry B on p. 4761-4774

Modeling Ensembles of Enzyme Reaction Pathways with Hi-MSM Reveals the Importance of Accounting for Pathway Diversity

Joseph Persichetti, Yang Jiang, Phillip Hudson, Edward O’Brien, Edward P. O'Brien, 2022, Journal of Physical Chemistry B on p. 9748-9758

Most-Cited Papers

Cotranslational Protein Folding inside the Ribosome Exit Tunnel

Ola B. Nilsson, Rickard Hedman, Jacopo Marino, Stephan Wickles, Lukas Bischoff, Magnus Johansson, Annika Müller-Lucks, Fabio Trovato, Joseph D. Puglisi, Edward P. O'Brien, Roland Beckmann, Gunnar von Heijne, 2015, Cell Reports on p. 1533-1540

Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding

Kristina Döring, Nabeel Ahmed, Trine Riemer, Harsha Garadi Suresh, Yevhen Vainshtein, Markus Habich, Jan Riemer, Matthias P. Mayer, Edward P. O'Brien, Günter Kramer, Bernd Bukau, 2017, Cell on p. 298-311.e20

Does SARS-CoV-2 bind to human ACE2 more strongly than does SARS-CoV?

Hoang Linh Nguyen, Pham Dang Lan, Nguyen Quoc Thai, Daniel A. Nissley, Edward P. O'Brien, Mai Suan Li, 2020, Journal of Physical Chemistry B on p. 7336-7347

How synonymous mutations alter enzyme structure and function over long timescales

Yang Jiang, Syam Neti, Ian Sitarik, P Pradhan, Philip To, Yingzi Xia, Stephen Fried, Squire J. Booker, Edward P. O’Brien, 2022, Nature Chemistry on p. 308-318

A chemical kinetic basis for measuring translation initiation and elongation rates from ribosome profiling data

Ajeet K. Sharma, Pietro Sormanni, Nabeel Ahmed, Prajwal Ciryam, Ulrike A. Friedrich, Günter Kramer, Edward P. O'Brien, 2019, PLoS Computational Biology

Kinetic and structural comparison of a protein’s cotranslational folding and refolding pathways

Avi J. Samelson, Eric Bolin, Shawn M. Costello, Ajeet K. Sharma, Edward P. O’Brien, Susan Marqusee, 2018, Science advances

Non-equilibrium coupling of protein structure and function to translation–elongation kinetics

Ajeet K. Sharma, Edward P. O'Brien, 2018, Current Opinion in Structural Biology on p. 94-103

Domain topology, stability, and translation speed determine mechanical force generation on the ribosome

Sarah E. Leininger, Fabio Trovato, Daniel A. Nissley, Edward P. O’Brien, 2019, Proceedings of the National Academy of Sciences of the United States of America on p. 5523-5532

Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding

Daniel A. Nissley, Ajeet K. Sharma, Nabeel Ahmed, Ulrike A. Friedrich, Günter Kramer, Bernd Bukau, Edward P. O'Brien, 2016, Nature Communications

Electrostatic Interactions Govern Extreme Nascent Protein Ejection Times from Ribosomes and Can Delay Ribosome Recycling

Daniel Nissley, Quyen Vu, Fabio Trovato, Nabeel Ahmed, Yang Jiang, Mai Li, Edward O’Brien, Edward P. O'Brien, 2020, Journal of the American Chemical Society on p. 6103-6110

News Articles Featuring Edward O’Brien

Apr 09, 2025

NCEMS working groups to answer molecular and cellular bioscience questions

The U.S. National Science Foundation National Synthesis Center for Emergence in the Molecular and Cellular Sciences at Penn State aims to drive multidisciplinary collaboration utilizing publicly available research data.

Full Article

Mar 14, 2025

Protein accidentally lassos itself, helping explain unusual refolding behavior

New study demonstrates a potential protein misfolding mechanism that could solve a decades-old mystery of why some proteins refold in a different pattern than expected.

Full Article

Nov 27, 2024

Heard on Campus: Launch of new center in molecular and cellular sciences, NCEMS

Reception celebrates new NSF-funded National Synthesis Center for Emergence in the Molecular and Cellular Sciences at Penn State.

Full Article

Oct 03, 2024

ICDS Day seeks to amplify synergy for interdisciplinary research opportunities

Oct. 23 event aims to bring together faculty, students and industry professionals to foster innovation and interdisciplinary collaboration.

Full Article

Sep 30, 2024

From vision to victory: Penn State's journey to a $20M NSF grant

The establishment of the National Synthesis Center for Emergence in the Molecular and Cellular Sciences (NCEMS) offers valuable lessons for future large-scale, multi-institutional proposals.

Full Article

Aug 13, 2024

NCEMS aims to ‘build a nationwide community' and address research barriers

The U.S. National Science Foundation (NSF) National Synthesis Center for Emergence in the Molecular and Cellular Sciences (NCEMS) at Penn State “will “bring scientists together from different disciplines to integrate diverse data sets to answer transformative scientific questions,” according to Justin Petucci, associate director of NCEMS and Research Innovations with Scientists and Engineers' (RISE) artificial intelligence and machine learning team lead.

Full Article

Apr 25, 2024

$20M NSF grant to support center to study how complex biological processes arise

A $20 million grant from the U.S. National Science Foundation (NSF) will support the establishment and operation of the National Synthesis Center for Emergence in the Molecular and Cellular Sciences (NCEMS) at Penn State.

Full Article

Jul 28, 2025

A 25-Year Mystery Solved: Scientists Discover Why Some Proteins Fold the “Wrong” Way

A new study reveals a possible protein misfolding mechanism that may resolve a long-standing mystery of why certain proteins refold into unexpected patterns.

Full Article