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Patricia Clark

Patricia Clark

The Rev. John Cardinal O'Hara, C.S.C. Professor of Chemistry and Biochemistry

Department of Chemical and Biomolecular Engineering

The Rev. John Cardinal O'Hara, C.S.C. Professor of Chemistry and Biochemistry
College of Engineering

Email: pclark1@nd.edu

Phone: 574-631-8353

Office: 445 Stepan Chemistry


B.S., Georgia Tech

PhD., UT Southwestern Medical Center

PostDoc Fellow, MIT


Professor Clark received her B.S. (chemistry, 1991) from Georgia Tech, Ph.D. (molecular biophysics, 1997) from UT Southwestern Medical Center and was an NIH NRSA postdoctoral fellow at MIT. She joined Notre Dame in 2001 as the Clare Boothe Luce Assistant Professor of Biochemistry.  Professor Clark has received a CAREER Award from NSF and a National Research Development Award from the American Heart Association. She has served on the Biophysical Society's Council, and is a member of the Editorial Board of Biophysical Journal.  She is the 2013 recipient of the Michael & Kate Bárány Award from the Biophysical Society.


Braselmann E., Chaney J.L. & Clark P.L. (2013) Folding the proteome. Trends in Biochemical Sciences 38, 336-343.

Braselmann E. & Clark P.L. (2012) Autotransporters: The cellular environment reshapes a folding mechanism to promote protein transport. Journal of Physical Chemistry Letters 3, 1063-1071.

Renn J.P., Junker M., Besingi R.N., Braselmann E. & Clark P.L. (2012) ATP-independent control of autotransporter virulence protein transport via the folding properties of the secreted protein. Chemistry & Biology 19, 287-296.

Bryan A.W., Starner-Kreinbrink J., Hosur R., Clark P.L. & Berger B. (2011) Structure-based prediction reveals capping motifs inhibit β-helix aggregation. Proceedings of the National Academy of Sciences USA 108, 11099-11104.

Ugrinov K.G. & Clark P.L. (2010) Co-translational folding increases GFP folding yield. Biophysical Journal 98, 1312-1320.

Clarke T.F. IV & Clark P.L. (2010) Increased incidence of rare codon clusters at 5’ and 3’ gene termini: Implications for function. BMC Genomics 11, 118.

Summary of Activities/Interests

Proteins are long flexible polymers of amino acids, yet each must fold into a complex 3D shape in order to carry out a specific catalytic, binding, or structural activity. Experiments with purified proteins have demonstrated that the information needed for a given protein to obtain its final folded structure is contained within the sequence of its amino acid residues. However, the rules that dictate how a given sequence will fold into a given structure are still unclear. Understanding the rules of protein folding is of utmost importance for predicting protein structure from genomic sequence data, designing novel proteins, and understanding how and why protein folding mechanisms can fail. Failure of protein folding mechanisms, often due to genetic mutations or adverse conditions such as thermal or chemical stress, is the cause of numerous human diseases including cystic fibrosis, Alzheimer's disease, juvenile cataracts, and many forms of cancer.

Research in the Clark laboratory is focused on two related topics. First, how are the rules for protein folding affected by their native environment, the cell? In the cell, proteins are synthesized in a vectorial fashion. The energy landscape for folding during chain synthesis (or secretion across a membrane) is hence quite different from the energy landscape for the folding of a full-length polypeptide chain. As a result, folding intermediates populated during refolding in vitro might be populated quite differently during vectorial folding. A particular interest in the Clark laboratory is the role of co-translational protein folding in suppressing chain misfolding and aggregation in vivo. A related interest is the display of virulence factors on the outer surface of pathogenic gram-negative bacteria. For example, these virulence proteins must fold only after secretion across two membranes; what prevents them from folding prematurely in the periplasm.

Second, what are the protein folding rules that govern the formation of β-sheet structure? β-sheets represent a type of regular, repeating protein structure, characterized by an extensive hydrogen bonding network between strands of amino acid residues. Contacts between individual amino acid residues in β-sheets often represent contacts quite distant in sequence. As a result, it has been extremely difficult to define simple rules for β-sheet formation, and we expect that high contact order will make many β-sheet topologies difficult (if not impossible) to form co-translationally. We are using an extremely simple β-sheet architecture, the parallel β-helix, as a model system for developing rules for β-sheet formation.