A. Keith Dunker
Professor, Informatics
- Phone
- 317-278-9236
- Office
- 410 W. 10th Street
HS 5000
Indianapolis, IN 46202-5122
Web
http://compbio.iupui.edu/dunker/
Other Titles
- Professor of Biochemistry and Molecular Biology, IU School of Medicine
- Director, Center for Computational Biology
Education
Post-doctorate, Molecular Biophysics, Yale University, New Haven, CT (1969-73)
Ph.D. Biophysics, University of Wisconsin, Madison (1969)
M.S. Physics, University of Wisconsin, Madison (1967)
B.S. Chemistry, University of California, Berkeley (1965)
Research Interests
The Central Dogma of molecular biology is that DNA sequence determines messenger RNA sequence, which in turn determines amino acid sequence. A given amino acid sequence then determines one, specific, unique 3 dimensional structure. The folded 3D structure is prerequisite for protein function. One of the central, unsolved problems in molecular biology is the code by which a given amino acid sequence determines a 3D fold. This is called the "protein folding problem."
We recently noticed that many proteins contain regions that apparently don't fold into specific structures, but rather remain as ensembles of structures. In many cases, the disorderliness of these regions is required for function; hence these regions are "natively disordered."
Since amino acid sequence is known to determine protein folding, we reasoned that sequence should determine disorder as well. To test this hypothesis, we used simple data analysis and neural networks. Our results, which may ultimately require a significant restructuring of the Central Dogma, suggest that nature is rich in natively disordered protein. These results encouraged us to consider possible roles of unfolded protein states in the realm of molecular biology. This trail has led to a new classification scheme for molecular recognition, a new classification scheme for structure/sequence relationships, and a proposed critical role for disordered regions in the evolution of molecular biological networks.
To locate these natively unfolded sequences in nature, we have developed PONDR (Predictors Of Natural Disordered Regions) a collection of various predictors that function from primary sequence information. PONDR results are available online. A comprehensive review regarding disordered proteins was written by Peter Wright and Jane Dyson, follow this link for the abstract.
Publications
Radivojac, P., Obradovic, Z., Brown, C.J., and Dunker, A.K. Improving sequence alignments for intrinsically disordered proteins. Pac. Symp. Biocomput. 7: 589-600 (2002).Brown, C.J., Takayama, S., Campen, A., Vise, P,. Marshall, T., Oldfield, C.J., and Dunker, A.K. Evolutionary rate heterogeneity in proteins with long disordered regions. J. Mol. Evol. 55: 102-107 (2002).
O’Connor, T., Lawson, J.D., Brown, C.J. and Dunker, A.K. Using disorder information to improve prediction of calmodulin binding targets. Internatl. Joint Conf. Neural Networks 5: 296-299 (2002).
Yang, J., Powers, J.R., Clark, S., Dunker, A.K. & Swanson, B.G. Hydrophobic probe binding of b-lactoglobulin in the native and molten globule induced by high pressure as affected by pH, KIO3 and N-ethylmaleimide. J. Agric. and Food Chem. 50: 5207-5214 (2002).
Iakoucheva, L.M., Brown, C.J., Lawson, J.D., Obradovic, Z., and Dunker, A.K. Intrinsic disorder in cell-signaling and cancer-associated proteins. J. Mol. Biol. 323:573-584 (2002).
Radivojac, P., Obradovic, Z., Brown, C.J. and Dunker A.K. Prediction of boundaries between intrinsically ordered and disordered protein. Pac. Symp. Biocomput. 8: 216-227 (2003).
Yang, J., Powers, J.R., Clark, S., Dunker, A.K. & Swanson, B.G. Ligand and flavor binding functional properties of b-lactoglobulin in the molten globule state induced by high pressure. J. Food Science 68: 444-452 (2003).
Smith, D.K., Radivojac, P., Obradovic, Z., Dunker, A.K., and Zhu, G. Improved amino acid flexibility parameters. Protein Science. 12: 1060-1072 (2003).
Park, H.J., Wu, S., Dunker, A.K., and Kang, C.H. Polymerization of calsequestrin: implications for calcium regulation. J. Biol. Chem. 278: 16176-16182 (2003).
Vucetic, S., Obradovic, Z., Brown, C.J., and Dunker, A.K. Flavors of protein disorder. Proteins: Structure, Function, Genetics, 52: 573-584 (2003).
Obradovic, Z., Kang, P., Vucetic, S., Radivojac, P., Brown, C. J., and Dunker, A. K. Predicting intrinsic disorder from amino acid sequence. Proteins: Structure, Function, Genetics. (In press, 2003).
Radivojac, P., Obradovic, Z., Smith, D.K., Zhu, G., Vucetic, S., Brown, C.J., Lawson, J.D., and Dunker, A. K. Protein flexibility and intrinsic disorder. Protein Science (In press, 2003).
Dunker, A.K., Iakoucheva, L.M., Brown, C.J., Lawson, J.D., and Obradovic, Z. Intrinsic disorder and protein function. Biochemistry. 41: 6573-6582 (2002).
Dunker, A.K., Brown, C.J., and Obradovic, Z. Identification and functions of usefully disordered proteins. Advances in Protein Chemistry 62: 25-49 (2002).
Uversky, V.N., Oldfield, C.J. Showing your ID: Intrinsic disorder as an ID for recognition, regulation, and cell signaling. TIBS (Submitted 2003).
