Kenneth Woycechowsky

Assistant Professor of Chemistry

Ken Woycechowsky

B.S. Penn State University

Ph.D. University of Wisconsin, Madison



Ken Woycechowsky's Lab Page

Ken Woycechowsky's PubMed Literature Search


Biological Chemistry Program

Biopolymers; Protein folding, assembly, and function; Mutagenesis


My group is interested in understanding the chemical and biological properties of proteins. We use protein engineering strategies to dissect structure-function relationships as well as to generate polypeptides with new and useful features. Problems of interest include protein self-assembly and the application of directed evolution to install novel binding or catalytic functions in initially inactive scaffolds.

The majority of proteins found in Nature undergo self-assembly. These assembly processes can be either discreet, giving closed oligomeric structures, or indefinite, producing linear polymers. Icosahedral capsids result from the former type of assembly and can be useful for the storage and transport of guest molecules (examples include viruses carrying nucleic acids or metal storage by ferritin). We are interested in understanding the structural basis of capsid formation. This knowledge is being applied to the engineering of novel encapsulations systems, which could be useful for drug delivery applications. Our other interest in protein self-assembly concerns amyloid-like fibrils, which are formed by bundles of indefinitely long beta-sheets. We are engineering variants of fibril-forming peptide sequences to better understand fibril stability and specificity, to develop new therapeutics for amyloid diseases, and to generate novel materials for biotechnology applications.

The incredible structural and functional diversity of natural proteins stems from ongoing cycles of mutation, selection, and amplification (i.e., evolution). Protein engineers have had much success mimicking natural evolution in the laboratory to tune protein activity and stability. However, the successful application of directed evolution usually requires that a significant amount of activity be present at the outset. The ability to confer new activities onto initially inactive precursors in a generic fashion via directed evolution would open the door to customized proteins on-demand, potentially giving rise to a new generation of catalysts, medicinal diagnostic reagents, and cell biological tools. We are utilizing a combination of in vitro selection techniques and large libraries of mutants to generate novel receptors and catalysts. The variants identified can be used as inputs for further rounds of evolutionary optimization and as subjects for detailed structure-function analysis.

The research undertaken in our group utilizes techniques that span the interface of chemistry and biology. We draw on concepts and methods from biochemistry, molecular/cellular biology, organic chemistry, and biophysics. This multi-disciplinary approach allows us to gain a more sophisticated view of how proteins work while also providing an exciting and rigorous training experience. 


  1. Woycechowsky KJ, Choutko A, Vamvaca K, Hilvert D (2008) Relative tolerance of an enzymatic molten globule and its thermostable counterpart to point mutation. Biochemistry 47:13489-13496
  2. Beld J, Woycechowsky KJ, Hilvert D (2008) Catalysis of oxidative protein folding by small-molecule diselenides. Biochemistry 47:6985-6987
  3. Toscano M, Woycechowsky KJ, Hilvert D (2007) Minimalist active-site redesign: teaching old enzymes new tricks. Angew. Chem. Int. Ed. 46:3212-3236
  4. Beld J, Woycechowsky KJ, Hilvert D (2007) Selenoglutathione: efficient oxidative protein folding by a diselenide. Biochemistry 46:5382-5390
  5. Woycechowsky KJ, Vamvaca K, Hilvert D (2007) Novel enzymes through design and evolution. Adv. Enzymol. Relat. Areas Mol. Biol. 75:241-294
  6. Woycechowsky KJ, Seebeck FP, Hilvert D (2006) Tunnel plasticity and quaternary structural integrity of a pentameric protein ring. Protein Sci. 15:1106-1114
  7. Seebeck FP, Woycechowsky KJ, Zhuang W, Rabe J, Hilvert D (2006) A simple tagging system for protein encapsulation. J. Am. Chem. Soc. 128:4516-4517
  8. Woycechowsky KJ, Hook BA, Raines RT (2003) Catalysis of protein folding by an immobilized small-molecule dithiol. Biotechnol. Prog. 19:1307-1314
  9. Woycechowsky KJ, Raines RT (2003) The CXC motif: a functional mimic of protein disulfide isomerase. Biochemistry 42:5387-5394
  10. Woycechowsky KJ, Wittrup KD, Raines RT (1999) A small-molecule catalyst of protein folding in vitro and in vivo. Chem. Biol. 6:871-879
Last Updated: 11/7/16