Proper folding of proteins is essential for their biological functions. In contrast, misfolding and aggregation of proteins have been implicated in a wide array of diseases, such as Alzheimer’s disease and Type II Diabetes. The primary research endeavor of our group is directed to understand the underlying mechanisms of protein folding and misfolding. A multidisciplinary approach, integrating organic chemistry, protein engineering and biophysics, will be employed to probe the physio-chemical basis of protein folding/misfolding processes. Detailed understanding of protein folding mechanisms will provide guidelines for protein structure prediction and design of unnatural functional polymers. Knowledge on protein misfolding will enable us to understand the pathologies of protein misfolding diseases and foster novel therapeutic strategies for disease treatment.

Representative Key Publications:

Hong Zheng, Kristofer Comeforo and Jianmin Gao, “Expanding the Fluorous Arsenal: Tetrafluorinated Phenylalanines for Protein Design”, J. Am. Chem. Soc. 2009, 131, 18-19.

Jianmin Gao, Daryl A. Bosco, Evan T. Powers, and Jeffery W. Kelly, “Localized Thermodynamic Coupling between Hydrogen Bonding and Microenvironment Polarity Significantly Stabilizes Proteins”, Nat. Struct. Mol. Biol., 2009, 16, in press.

Michelle R. Bunagan, Jianmin Gao, Jeffery W. Kelly, and Feng Gai “Probing the Folding Transition State Structure of the Villin Headpiece Subdomain via Sidechain and Backbone Mutagenesis”, J. Am. Chem. Soc. 2009, 131, 7470-7476.