Interdisciplinary Life Science - PULSe Great research is a matter of choice

Chiwook Park

Chiwook Park Profile Picture

Associate Professor in MCMP
Postdoc., University of California, Berkeley (Dr. Susan Marqusee), 2001-2005
Ph.D., University of Wisconsin-Madison (Dr. Ronald T. Raines), 2000
M.S., Seoul National University, 1993
B.S., Seoul National University, 1991


Contact Info:

park6@purdue.edu
765-496-7513


Training Group(s):
Computational and Systems Biology
Biomolecular Structure and Biophysics


Current Research Interests:

Proteins are dynamic molecules. Even under native conditions, they do not adopt a single static conformation. Rather, they access many different conformations in their native state ensemble. This native state ensemble includes small fluctuations around the native conformation, partially unfolded forms, and even globally unfolded forms. The distribution of these conformations and the kinetic barriers between the conformational states define the conformational energy landscapes of proteins. My research interest is investigating conformational energy landscapes of proteins and deciphering the relationship between the energetics of proteins and their biochemical functions, such as catalysis, signal transduction, and ligand binding. We use proteolysis as a major tool to probe protein structures and dynamics as well as conventional spectroscopic methods. We also use proteomics extensively for investigating energy landscapes of proteins on a system level.

Investigation of conformational energy landscape of proteins on a proteomic scale

With the advent of the postgenomic and proteomic era, we face new challenges and new opportunities in protein folding studies. Can we obtain information on the energetics and dynamics of proteins on a proteomic scale? Can we study the relationship between the energetics and function of proteins at a system level? To address these issues, we use proteolysis as a structural probe. Conventional biophysical approaches using spectroscopy and calorimetry allow us to study only one protein at a time. However, by using proteolysis and proteomics tools, we can study energetics of multitude of proteins in a proteome at the same time. Currently, we are attempting to determine global stabilities and unfolding kinetics of proteins on a proteomic scale. This research will allow us to understand why some proteins are more stable than the others and how evolution has shaped the distribution of thermodynamic and kinetic stabilities of proteins in a proteome.

Identification of cellular drug targets by proteolysis

Energy landscapes of proteins are perturbed by interaction with drug molecules. By monitoring these changes on a proteomic scale using proteolysis, we can identify cellular targets interacting with drug molecules. The cellular targets of effective drugs are often unknown. Moreover, novel chemicals affecting cellular activities are discovered at a tremendous speed by chemical genetics. By knowing the cellular target, we can design better drugs based on the structure and screen other drug candidates in vitro. In addition, these drugs serve as research tools to control cellular functions of the target.

Investigation of energetic properties of membrane proteins

In spite of functional importance of membrane proteins, conformational energetics of membrane protein structures are not well known yet. Expression and purification of membrane proteins for biophysical studies are still quite challenging. Using proteolysis as a structural tools, we attempt to monitor folding and unfolding of membrane proteins without purifying the proteins. By determining thermodynamic and kinetic stabilities of endogenous membrane proteins in cell lysates, we will investigate the energetic principles governing membrane protein folding. Also, we will determine ligand binding affinities to membrane receptors based on the increase in stability upon ligand binding. Direct investigations of endogeous membrane proteins without purification will allow us to pursue many exciting research opportunities on membrane proteins which have not been possible with conventional methods.



Selected Publications:

Pei-Fen Liu, Daisuke Kihara, and Chiwook Park (2011) Energetics-based Discovery of Protein–Ligand Interactions on a Proteomic Scale, Journal of Molecular Biology 408, 147-162.  

Jonathan P Schlebach, Moon-Soo Kim, Nathan H Joh, James U Bowie, and Chiwook Park (2011) Probing Membrane Protein Unfolding with Pulse Proteolysis. Journal of Molecular Biology 406, 545-551. (Cover Article)  

Youngil Chang and Chiwook Park (2009) Mapping Transient Partial Unfolding by Protein Engineering and Native State Proteolysis. Journal of Molecular Biology 393, 543-556.  

Pei-Fen Liu, Larisa Avramova, and Chiwook Park (2009) Revisiting Absorbance at 230 nm as a Protein Unfolding Probe. Analytical Biochemistry 389, 165-170.  

Kiwon Youn and Chiwook Park (2009) Investigating the Effect of Temperature on Transient Partial Unfolding by Proteolysis. Protein and Peptide Letters 16, 1093-1097.  

Moon-Soo Kim, Jiao Song, and Chiwook Park (2009) Determination of Protein Stability in Cell Lysates using Pulse Proteolysis and Western Blotting. Protein Science 18, 1051-1059.  

Yu-Ran Na and Chiwook Park (2009) Investigating Protein Unfolding Kinetics by Pulse Proteolysis. Protein Science 18, 268-276.  

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