T. K. Li Professor of Medical Research
Department of Biochemistry and Molecular Biology
Professor of Informatics
Director of Center for Computational Biology and Bioinformatics

Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
Health Information and Translational Sciences Building
410 W. 10th Street, HS5000
Indianapolis, Indiana 46202-3011

Phone: (317) 278-9220
Facsimile: (317) 278-9217
E-mail: kedunker@iupui.edu

B.S., 1965 , Chemistry, University of California, Berkeley, CA
M.S., 1967, Physics, University of Wisconsin, Madison, WI
Ph.D., 1969, Biophysics, University of Wisconsin, Madison, WI
Postdoctoral, 1969-73,  Molecular Biophysics, Yale University, New Haven, CT

Area of Study

Understanding intrinsically disordered proteins using bioinformatics approaches and laboratory experiments.   More details...

Selected Recent Publications

Dunker, A.K. and Kriwacki, R.W. The Orderly Chaos of Proteins, Scientific American, April 2011, pp 68-73.

Dixon, S.E., Mhatti, M.M., Uversky, V.N., Dunker, A.K., and Sullivan, W.J. Jr. Regions of intrinsic disorder help identify a novel nuclear localization signal in Toxoplama gondii histone acetyltransferase TgGCN5-B. Mol. Biochem Parasitol 175: 192-195 (2011)

Sanchez, E.J., Munske, G.R., Criswell, A., Milting, H., Dunker, A.K., and Kang, C.H. Phosphorylation of human calsequestrin: implications for calcium regulation. Mol Cell Biochem. 353: 195-204 (2011)

Brown, C.B., Johnson, A.K., Daughdrill, G.W. and Dunker, A.K. Evolution and disorder. Current Opin. Struct. Biol. 21: 441-446 (2011). 

Dunker, A.K. and Gough, J. Sequences and topology: intrinsic disorder in the evolving universe of protein structure. Current Opin. Struct. Biol. 21: 1-3 (2011) – The figure in this paper was selected for the cover of this issue.

Mizianty, M.J., Thang, T., Zhou, Y., Dunker, A.K., Uversky, V.N., and Kurgan, L. In-silico prediction of disorder content using hybrid sequence representation. BMC Bioinformatics  12: 245 (2011)

Xue, B., Soeria-Atmadja, D., Gustafsson, M.G., Hammerling, U., Dunker, A. K., and Uversky, V. N. Abundance and functional roles of intrinsic disorder in allergenic proteins and allergenic representative peptides. Proteins 79: 2595-2606 (2011)

Xue B., Williams R.W., Oldfield C.J., Goh G.K.-M., Dunker A.K., Uversky V.N. Do viral proteins possess unique features? In: Flexible Viruses: Structural Disorder in Viral Proteins (Uversky V.N., Longhi S., Eds.) In The Wiley Series in Protein and Peptide Science (Uversky V.N. series Ed.), John Wiley & Sons, Inc, Hoboken, New Jersey, USA.pp 1-34 (2011)

Goh G.K.-M., Dunker A.K., Uversky V.N. Structural disorder in proteins from influenza virus. In: Flexible Viruses: Structural Disorder in Viral Proteins (Uversky V.N., Longhi S., Eds.) In The Wiley Series in Protein and Peptide Science (Uversky V.N. series Ed.), John Wiley & Sons, Inc, Hoboken, New Jersey, USA. Pp. 143-167 (2011)

Goh G.K.-M., Xue B., Dunker A.K., Uversky V.N. Structural disorder in matrix proteins from HIV-related viruses. In: Flexible Viruses: Structural Disorder in Viral Proteins (Uversky V.N., Longhi S., Eds.) In The Wiley Series in Protein and Peptide Science (Uversky V.N. series Ed.), John Wiley & Sons, Inc, Hoboken, New Jersey, USA. Pp 169-200 (2011)

Xue, B. Oldfield, C.J., Van, Y.Y., Dunker, A.K., and Uversky, V.N. Protein intrinsic disorder and induced pluripotent stem cells  Mol Biosystems (2011) (Epub ahead of print)

Sun, X., Xue, B., Jones, W.T.,  Rikkerink, E., Dunker, A.K., and Uversky, V.N., A functionally required unfoldome from the plant kingdom: intrinsically disordered N-terminal domains of GRAS proteins are involved in molecular recognition during plant development Plant Molecular Biology 77: 205-223 (2011)

Liu, J., Jolly, R.A., Smith, A.K., Searfoss, G.H., Goldstein, K.M., Uversky, V.N., Dunker, K., Li, S., Thomas, C.E., and Wei, T. Predictive power estimation algorithm (PPEA), a new algorithm to reduce overfitting for genomic biomarker discovery. PLOS One 6: e24233 (2011)

Huang, F., Oldfield, C., Meng, J., Hsu, W. Xue, B., Uversky, V.N.,Romero, P.,  and Dunker, A.K. Subclassifying disordered protein by the CH-CDF Plot Method. Pac. Symp. Biocomput. (In Press)

Hsu, W.L., Oldfield, C., Meng, J., Huang, F., Xue, B., Uversky, V.N., Romero, P., Dunker, A.K. Intrinsic disorder and protein-protein interactions. Pac. Symp. Biocomput. (In Press)

Ghalwash, M.F., Dunker, A.K., and Obradovic, Z. Uncertainty analysis in protein disorder prediction. Mol BioSystems (In Press)

Zhang, T., Faraggi, E., Xue, B., Dunker, A.K., Uversky, V.N., and Zhou, Y. Accurate prediction of short and long disordered regions by a single neural-network based method.  J. Biomol. Struct. Dyn. (2011) (In Press)

Di Mauro, E., Dunker, A. K., and Trifonov, E. Disorder to order, non-life to life.  In the beginning there was … a mistake. in Genesis: Origin of Life on Earth and Other Planets (Seckbach, J. and Gordon, R., eds) in the book series Cellular Origin, Life in Extreme Habitats, and Astrobiology. Springer, New York (2011) (In press)

Dunker, A.K., and Uversky, V.N. Intrinsically Disordered Proteins. in Comprehensive Biophysics (Ed. by E. H. Egelman) Elsevier, Oxford, England. (2011)  (In Press)

Dunker A.K., Uversky V.N. Why are we interested in unfolded peptides and proteins? In: Folding, Misfolding and Nonfolding of Peptides and Small Proteins (Schweitzer-Stenner R. Ed.) In The Wiley Series in Protein and Peptide Science (Uversky V.N. series Ed.), John Wiley & Sons, Inc, Hoboken, New Jersey, USA. (2011) (In Press)

Uversky V.N., Oldfield C.J., Xue B., Dunker A.K. Binding promiscuity of unfolded peptides. In: Folding, Misfolding and Nonfolding of Peptides and Small Proteins (Schweitzer-Stenner R. Ed.) In The Wiley Series in Protein and Peptide Science (Uversky V.N. series Ed.), John Wiley & Sons, Inc, Hoboken, New Jersey, USA. (2011) (In Press)

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Books Edited (2008 - Present)

Altman, R.B., Dunker, A.K., Hunter, L, Jung, T., and Klein, T.  Pacific Symposium on Biocomputing  World Scientific Press, Singapore (2008).

Longhi S.  Measles Virus Nucleoprotein. In series “Intrinsically Disordered Proteins” (Uversky V.N., Dunker A.K., series Eds.). Nova Science Publishers, Inc., Hauppauge, NY, USA, (2008)

Boggs J.M. (2008) Myelin Basic Protein. In series “Intrinsically Disordered Proteins” (Uversky V.N., Dunker A.K., series Eds.). Nova Science Publishers, Inc., Hauppauge, NY, USA, (ISBN 978-1-60456-699-4).

Altman, R.B., Dunker, A.K., Hunter, L, Jung, T., and Klein, T.  Pacific Symposium on Biocomputing  World Scientific Press, Singapore (2009).

Altman, R.B., Dunker, A.K., Hunter, L, Jung, T., and Klein, T.  Pacific Symposium on Biocomputing  World Scientific Press, Singapore (2010).

Uversky, V.N. and Dunker, A.K. Methods in Molecular Biology: Experimental tools for the Analysis of Intrinsically Disordered Protein, Volume 2. Humana Press  (New York, NY, USA) (In Press)

Uversky, V.N. and Dunker, A.K. Methods in Molecular Biology: Experimental tools for the Analysis of Intrinsically Disordered Protein, Volume 1. Humana Press  (New York, NY, USA) (In Press)

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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." This overall process is sometimes called the sequence → structure → function paradigm.

More than a decade ago we noticed that many proteins contain regions that apparently don't fold into specific structures, but rather remain as ensembles of structures. In some cases entire proteins lack even one region of specific 3D structure. In many cases, the disorderliness of these proteins and 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 data analysis and bioinformatics approaches. Our results, which are requiring 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.

Overall, our studies suggest sequence →  to structure →  to function describes enzymes while sequence →  disordered ensemble →  to function describes proteins and protein regions that carry out signal transduction.

To locate these natively unfolded sequences in nature, we have developed several PONDRs (Predictors Of Natural Disordered Regions) a collection of predictors that use primary sequence information to identify whether is given region is likely in a structured or in a disordered region. PONDR can be used online, and can be accessed here. Several reviews describing these natively disordered proteins have been written, follow this link to find a recent one that emphasizes the functions of these proteins.