A. Keith Dunker
Director of Bioinformatics
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.
