Edward P. O’Brien, Ph.D. Assistant Professor Department of 402 Chemistry Bldg. Pennsylvania State University Phone: 814-867-5100 University Park, PA. 16802 Email: [email protected]

Education 1/2009 – 12/2013 Postdoctoral Fellow, University of Cambridge Advisor, Prof. Christopher Dobson Co-advisor, Prof. Michele Vendruscolo

11/2013 Training, “Advanced Sequencing Technologies and Applications Course” Cold Spring Harbor Laboratory

9/2002 – 10/2008 Ph.D., Chemical University of Maryland College Park Advisor, Prof. Dave Thirumalai Co-advisor, PI Bernard Brooks (National Institutes of Health) Thesis: and formation in various environments

9/1998 – 5/2002 B.S., Biochemistry, minors in Mathematics and Physics University of the Sciences in Philadelphia Graduated with honors (Magna Cum Laude)

Research Experience 1/2014 – present Assistant Professor, Department of Chemistry, Pennsylvania State University, University Park.

1/2009 – 12/2013 NSF and EPSRC Postdoctoral Research Fellow, Department of Chemistry, University of Cambridge. Advisor, Prof. Christopher Dobson; Co-advisor, Prof. Michele Vendruscolo.

9/2002 – 10/2008 NIH Graduate Research Fellow in , University of Maryland College Park. Advisor, Dave Thirumalai; Co-advisor, Bernard Brooks (NIH).

6/2007 – 8/2007 NSF EAPSI Graduate Research Fellow, Department of Physics, Nagoya University, Japan. Advisor, Yuko Okamoto.

5/2002 – 9/2002 Schering-Plough Summer Research Fellow, University of the Sciences in Philadelphia. Advisor, Guillermo Moyna.

5/2001 – 9/2001 Summer Researcher, The Scripps Research Institute. Advisor, Gary Suizdak.

Grants and Fellowships 8/2016 – 7/2019 National Science Foundation - Deutsche Forschungsgemeinschaft CAREER Supplement. PI Ed O’Brien. 3 years, totaling $21,000. 6/2016 – 5/2021 National Science Foundation CAREER Grant. PI Ed O’Brien. 5 years, totaling $900,000. 5/2015 – 5/2018 Human Frontier’s Science Program Research Grant. PI Ed O’Brien; Co-PI, Bernd Bukau. 3 years, totaling $750,000 ($375k for PI). 5/2013 Biotechnology and Biology Sciences Research Council (UK) David Phillips Fellowship “A systems approach to understanding and manipulating In vivo

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nascent protein behavior at the molecular and cellular levels”. 5 years, totaling $1,700,000. Declined fellowship to start position at Penn State. 5/2013 The Royal Society (UK) University Research Fellowship “Model-based prediction of nascent protein behaviour in cells”. 5 years, totaling $1,000,000. Declined fellowship to start position at Penn State. 1/2012 – 1/2015 Engineering and Physical Sciences Research Council (UK) Research co- investigator on a grant that I wrote entitled “Tools for Understanding and Controlling the Non-Equilibrium Self-Assembly of Multi-Component Macromolecular Systems”. 3 years, totaling $473,000. 1/2009 – 1/2012 National Science Foundation Postdoctoral Research Fellowship in Bioinformatics. 3 years, totaling $187,000. 9/2002 – 10/2008 National Institutes of Health GPP Graduate Research Fellowship in Biophysics. 6/2007 – 8/2007 National Science Foundation East Asia and Pacific Summer Institutes Fellowship.

Awards 6/2008 Best Poster Award, Gordon Research Conference on Biopolymers, “Osmolyte and denaturant effects on proteins are accurately predicted with the Molecular Transfer Model”. 3/2008 Best Poster Award, National Institutes of Health NHLBI Fellows Retreat, “Thermodynamic basis for the Dock-Lock mechanism of amyloid formation”. 5/2002 Lewis A. Reber Award for Excellence in Research, University of the Sciences in Philadelphia. 2001 Scherling-Plough sponsored Summer Research Fellowship. 1999, 2000 Merck sponsored Summer Research Fellowships.

Professional Service and Outreach 6/2016 Upward Bound Math and Science Program. 6-week program in which four high- school students from underserved communities carried out research in the O’Brien Lab. Penn State, PA. 2/2016 NSF EAPSI Grant Review panel in Mathematical and Physical Sciences. 2 days long, Teleconference, Arlington, VA. 2/2016 Elected Program Chair, 60th Biophysical Society National Meeting, Biopolymers In Vivo Sub subgroup. Los Angeles, CA. 2/2015 NSF EAPSI Grant Review panel in Mathematical and Physical Sciences. 2 days long, NSF Headquarters, Arlington, VA. 4/2015 Poster Judge. Penn State Undergraduate Research Exhibition. University Park, PA. 1/2015 NSF EAPSI Grant Review panel in Mathematical and Physical Sciences. 2 days long, NSF Headquarters, Arlington, VA. 8/2014 Organizer of the CECAM conference “Modeling Cellular Life: From single molecules to cellular function.” 4 day conference held in Lausanne, Switzerland. 2/2014 Session Chair on RNA dynamics at the Biophysical Society National Meeting, San Francisco, CA. 1/2014 NSF EAPSI Grant Review panel in Mathematical and Physical Sciences. 2 days long, NSF Headquarters, Arlington, VA. 12/2012 Co-organizer for the 23rd Annual Molecular Chaperone Club Meeting, University of Cambridge, UK. 5/2012 Organizer of the 3-day CECAM workshop on “Ribosome-associated protein folding: Translation, auxiliary factors, and translocation,” Lausanne, Switzerland. 1/2012 Discussion leader at the Gordon Research Seminar in Protein Folding, Ventura, CA. Page 2 of 6

Teaching Experience Spring 2017 Lecturer, CHEM 110: “Introductory Chemistry” Fall 2016 Lecturer, CHEM 540: “Biophysical Chemistry” Spring 2016 Lecturer, CHEM 110: “Introductory Chemistry” Fall 2015 Lecturer, CHEM 540: “Biophysical Chemistry” Fall 2014 Lecturer, CHEM 540: “Biophysical Chemistry” Fall 2012 Senior undergraduate course: “Computer simulation methods in chemistry and physics,” University of Cambridge. Taught six lectures on molecular dynamics methods. Fall 2009 Teaching assistant in the Theoretical Chemistry Lab, University of Cambridge. Covered topics including Huckel theory, isomerization, and magnetic phase transitions.

Journal Reviewer Activity (past 3 years) Nature Communications Journal of the American Chemical Society Journal of Chemical Physics Journal of Physical Chemistry B Nucleic Acids Research FEBS Letters Proteins: Structure, Function, and Bioinformatics Protein Science Langmuir European Biophysics Journal Israel Journal of Chemistry Computational and Mathematical Methods in Medicine

Professional Society Affiliations American Physical Society American Chemical Society Biophysical Society

Publications under review (* indicates corresponding author) 31. F. Trovato and E. P. O’Brien*. “Fast-elongation rates promote nascent-protein folding by reducing the probability of pathways involving misfolded conformations” Under review. 30. A. Sharma and E. P. O’Brien*. “Increasing the rate of protein production can decrease the rate of functional protein production” Under review.

Publications (* indicates corresponding author) 29. F. Trovato and E. P. O’Brien*. “Insights into co-translational nascent protein behavior from computer simulations” Annu. Rev. Biophys., 2016. 45, 345-371. 28. D. A. Nissley and E. P. O’Brien. “Altered co-translational processing plays a role in Huntington’s pathogenesis - A hypothesis” Front. Mol. Neurosci., 2016. 9:54. 27. D. A. Nissley, A. K. Sharma, N. Ahmed, U. Friedrich, G. Kramer, B. Bukau and E. P. O’Brien*. “Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding” Nat. Commun., 2016. 7, 10341. 26. A. Sharma, B. Bukau and E. P. O’Brien*. “The physical origins of codon positions that strongly influence co-translational folding: A method for controlling nascent-protein folding” J. Am. Chem. Soc., 2016. 138(4), 1180-1195.

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25. O. B. Nilsson, R. Hedman, J. Marino, S. Wickles, L. Bischoff, M. Johansson, A. Muller-Lucks, F. Trovato, J. D. Puglisi, E. P. O’Brien*, R. Beckmann and G. von Heijne. “Co-translational protein folding inside the ribosome exit tunnel” Cell Rep., 2015. 12, 1533-1540. 24. L. Caniparolli and E. P. O’Brien*. “Modeling the effect of codon translation rates on co-translational protein folding mechanisms of arbitrary complexity” J. Chem. Phys., 2015. 142, 145102. 23. D. A. Nissley and E. P. O’Brien*. “Timing is everything: Unifying codon translation rates and nascent proteome behavior” J. Am. Chem. Soc., 2014. 136, 17892-17898. 22. E. P. O’Brien*, P. Ciryam, M. Vendruscolo and C. M. Dobson. “Understanding the influence of codon translation rates on cotranslational protein folding” Acc. Chem. Res., 2014. 47, 1536-1544. 21. E. P. O’Brien*, M. Vendruscolo and C. M. Dobson. “Kinetic modeling indicates that fast translating codons can coordinate cotranslational folding by helping avoid misfolded intermediates” Nature Communications, 2014. 5, 2988. 20. P. Ciryam, R. I. Morimoto, M. Vendruscolo, C. M. Dobson and E. P. O’Brien*. “In vivo translation rates can substantially delay the cotranslational folding of the E. coli cytosolic proteome” Proc. Natl. Acad. Sci. U.S.A., 2013. 110, E132-E140.  Highlighted in the journal Biopolymers 99(4):v.  Highlighted on the NSF’s SEE Innovation website. 19. D. Thirumalai, Z. Liu, E. P. O’Brien and G. Reddy. “Protein folding: From theory to practice” Curr. Opin. Struc. Biol., 2013. 23, 22-29. 18. E. P. O’Brien, J. Christodoulou, M. Vendruscolo and C. M. Dobson. “Trigger factor slows co- translational folding through kinetic trapping while sterically protecting the nascent chain from aberrant cytosolic interactions” J. Am. Chem. Soc., 2012. 134, 10920-10932.  Highlighted in JACS Spotlights 134:12321. 17. E. P. O’Brien, M. Vendruscolo and C. M. Dobson. “Prediction of variable translation rate effects on co-translational folding” Nature Communications, 2012. 3, 868.  Highlighted on the NSF’s SEE Innovation website. 16. E. P. O’Brien, B. R. Brooks and D. Thirumalai. “Effects of pH on proteins: Predictions for ensemble and single molecule pulling experiments” J. Am. Chem. Soc., 2012. 134, 979-987. 15. E. P. O’Brien, J. Christodoulou, M. Vendruscolo and C. M. Dobson. “New scenarios of protein folding can occur on the ribosome” J. Am. Chem. Soc., 2011. 133, 513-526.  Recommended on the Faculty of 1000 website. 14. Z. Liu, G. Reddy, E. P. O’Brien and D. Thirumalai. “Denaturant dependent folding of globular proteins: Collapse kinetics and chevron plots” Proc. Natl. Acad. Sci. U.S.A., 2011. 108, 7787-7792. 13. E. P. O’Brien, J. E. Straub, B. R. Brooks and D. Thirumalai. “Influence of nanoparticle size and shape on oligomer formation of an amyloidogenic peptide” J. Phys. Chem. Letters, 2011. 10, 1171- 1177. 12. E. P. O’Brien, S. T. D. Hsu, J. Christodoulou, M. Vendruscolo and C. M. Dobson. “Transient tertiary structure formation within the ribosome exit port” J. Am. Chem. Soc., 2010. 132, 16928-16937. 11. D. Thirumalai, E. P. O’Brien, G. Morrison and C. H. Hyeon. “Theoretical perspectives on protein folding” Annu. Rev. Biophys., 2010. 39, 159-183. 10. E. P. O’Brien, Y. Okamoto, J. E. Straub, B. R. Brooks and D. Thirumalai. “Thermodynamic perspective on the dock-lock growth mechanism of amyloid fibrils” J. Phys. Chem. B, 2009. 113, 14421-14430. 9. E. P. O’Brien, B. R. Brooks and D. Thirumalai. “Molecular origin of constant m-values, denatured state collapse, and residue-dependent transition midpoints in globular proteins” Biochem., 2009. 48, 3743–3754. 8. E. P. O’Brien, G. Morrison, B. R. Brooks and D. Thirumalai. “How accurate are polymer models in the analysis of Forster resonance energy transfer experiments on proteins?” J. Chem. Phys., 2009. 130, 124903. 7. E. P. O’Brien, G. Stan, D. Thirumalai and B. R. Brooks. “Factors governing helix formation in peptides confined to carbon nanotubes” Nano Letters, 2008. 8, 3702–3708.

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6. E. P. O’Brien, G. Ziv, G. Haran, B. R. Brooks and D. Thirumalai. “Effects of denaturants and osmolytes on proteins are accurately predicted by the molecular transfer model” Proc. Natl. Acad. Sci. U.S.A., 2008. 105, 13403–13408. 5. E. P. O’Brien, R. I. Dima, B. R. Brooks and D. Thirumalai. “Interactions between hydrophobic and ionic solutes in aqueous guanidinium chloride and urea solutions: Lessons for protein denaturation mechanism” J. Am. Chem. Soc., 2007. 129, 7346–7353. 4. K. Maksim, L. Mai Suan, E. P. O’Brien, H. Chin-Kun and D. Thirumalai. “Effect of finite size on cooperativity and rates of protein folding” J. Phys. Chem. A, 2006. 110, 671–676. 3. E. P. O’Brien and G. Moyna. “Use of 13C chemical shift surfaces in the study of carbohydrate conformation. Application to cyclodextrins in the solid state and in solution” Carbohydr. Res., 2004. 339, 87–96. 2. C. W. Swalina, E. P. O’Brien and G. Moyna. “Study of the temperature dependent conformational averaging of 1H NMR resonances in vinylcyclopropane through the use of ab initio methodology and Boltzmann statistics” Magn. Reson. Chem., 2002. 40, 195–201. 1. D. Davis, E. P. O’Brien and C. Bentzley. “Analysis of the degradation of DNA strands during the freezing/thawing process using MALDI-MS” Analy. Chem., 2000. 72, 5092–5096.

Talks (over 40 invited and contributed talks) 05/2017 “From Computational Biophysics to Systems Biology” Meeting, Cincinnati, OH. 04/2017 “Spotlight talk” at the ASBMB National Meeting, Chicago, IL. 11/2016 Third International Conference on Computational Science and Engineering, Saigon, Vietnam. 05/2016 Queen Mary College, London, UK. 02/2016 Biophysical Society 60th National Meeting, Los Angeles, CA. 01/2016 Gordon Research Conference: Protein Folding Dynamics, Galveston, TX. 10/2015 CECAM workshop, Tel Aviv University, Tel Aviv, Israel. 10/2015 North East Structure Symposium, University of Connecticut, Mansfield, CN. 08/2015 Symposium, Institute for Computational Science and Technology, Saigon, Vietnam. 08/2015 International Workshop on Theoretical and Computational Physics, Da Lat, Vietnam. 07/2015 Mini-symposium at 10th European Biophysics Congress, Dresden, Germany. 06/2014 Colloquium Talk, University of the Sciences, Philadelphia, PA. 02/2014 Biophysical Society 58th National Meeting, San Francisco, CA. 10/2013 ZMBH Colloquium, University of Heidelberg, Germany. 02/2013 Bioinformatics Program, Boston University, MA. 02/2013 Department of Chemistry, Massachusetts Institute of Technology, MA. 02/2013 Department of Biochemistry and Biophysics, University of Minnesota, MN. 01/2013 Department of Chemistry, Pennsylvania State University, PA. 12/2012 Department of Bioengineering, Rice University, TX. 12/2012 Department of Chemistry, Yale University, CN. 12/2012 Earl Statdman Lecture in Biophysics, National Institutes of Health, MD. 08/2012 American Chemical Society 244th National Meeting, Philadelphia, PA. 05/2012 CECAM conference on Ribosome Associated Protein Folding, Lausanne, Switzerland. 02/2012 Department of Biophysics, Johns Hopkins University, Baltimore, MD. 01/2012 Gordon Research Conference on Protein Folding Dynamics, Ventura, CA. 01/2012 Department of Biophysics, University of Michigan, Ann Arbor, MI. 12/2011 22nd Molecular Chaperone Club Meeting, University College London, UK. 12/2011 Systems and Computational Biology Colloquium, Albert Einstein College of Medicine, New York, NY. 11/2011 Theory Colloquium, Department of Chemistry, University of Cambridge, UK. 09/2011 Department of Biochemistry, University of Potsdam, Germany. 08/2011 American Chemical Society 242nd National Meeting, Denver, CO. 03/2011 Biophysical Society 55th National Meeting, Baltimore, MD. 06/2010 Molecular and Nanophysics Group Colloquium, University of Leeds, UK. 05/2010 Ribosomes 2010 Meeting, Orvieto, Italy. Page 5 of 6

03/2010 ZMBH Colloquium, University of Heidelberg, Germany. 03/2010 American Chemical Society 239th National Meeting, San Francisco, CA. 03/2010 American Physical Society March Meeting, Portland, OR. 01/2010 Department of Physiology, University of Pennsylvania, Philadelphia, PA. 01/2010 Gordon Research Seminar on Protein Folding Dynamics, Ventura, CA. 12/2009 20th Molecular Chaperone Club Meeting, University of Warwick, UK. 07/2009 Centre de Biochimie Structurale symposium. University of Montpellier, France. 02/2009 Biophysics Colloquium. Department of Chemistry, University of Cambridge, UK. 05/2008 Laboratory of Physical and Structural Biology, NIHHD. National Institutes of Health, Bethesda, MD. 02/2008 Biophysics Colloquium. Department of Physics, University of the Sciences in Philadelphia, PA. 01/2008 Structural Biology and Molecular Biophysics Journal Club, University of Texas Medical Branch, Galveston, TX. 03/2008 6th Annual NIH-NHLBI Fellows Retreat, Annapolis, MD. 10/2007 Department of Bioinformatics and Computational Biology Seminar Series, George Mason University, VA. 09/2006 American Chemical Society 232nd National Meeting, San Francisco, CA. 04/2006 3rd Annual G.P.P. Research Symposium, National Institutes of Health, Bethesda, MD.

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