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Conference Program
 
Intrinsically Disordered Proteins
Introducing Unfoldome and Unfoldomics
July 11-16, 2010
Davidson College
Davidson, NC

Recent studies revealed that functional proteins without unique 3-D structures are highly abundant in nature. These intrinsically disordered proteins (IDPs) possess a number of crucial biological functions that are complementary to functions of structured (ordered) proteins. In any given organism, IDPs constitute a functionally broad and densely populated unfoldome; i.e., a set of unstructured proteins in a proteome. Being structurally and functionally very different from ordered proteins, IDPs require special experimental and computational tools for their identification and analyses. These specific investigative approaches underlie unfoldomics.

IDPs are common across the three domains of life, being especially abundant in the eukaryotic proteomes. Signaling sequences and sites of posttranslational modifications are located within regions of intrinsic disorder. Disorder-to-order transitions in an IDP are coupled with the adoption of different structures in complexes with different partners. The intrinsic flexibility of IDPs helps different disordered regions to bind to a common binding site on a common partner. This binding diversity plays important roles in both protein-protein interaction networks and likely also in gene regulation networks. Such disorder-based signaling is further modulated in multicellular eukaryotes by alternative splicing, for which splicing events map to regions of disorder much more often than to regions of structure. The combination of disorder and alternative splicing is proposed to provide a mechanism for easily "trying out" different signaling pathways, thereby providing the mechanism for generating signaling diversity and enabling the evolution of cell differentiation and multicellularity. Finally, several small molecules-potential drugs have been shown to act by blocking protein-protein interactions involving intrinsic disorder of one of the partners.

Intrinsically Disordered Proteins GRC provides a forum for the discussion of IDPs, with topics including but not limited to experimental and theoretical studies of their intrinsically flexible state, mechanisms of their interactions, their functional roles in biological systems, and their potential involvement into the pathogenesis of conformational and other diseases. This GRC will unite participants from all scientific disciplines with an interest in broadening our understanding of IDPs, ranging from biophysical studies of individual proteins to genomic and proteomic studies in whole organisms, to biomedical investigations on the molecular mechanisms of many human diseases.


Contributors

SUNDAY
1:00 pm - 8:00 pmArrival and Check-in (Office Closed 6:00 pm - 7:45 pm)
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmINTRODUCTION TO UNFOLDOME AND UNFOLDOMICS
Discussion Leader: Rohit Pappu (Washington University, St.Louis, USA)
7:40 pm - 8:20 pm Peter Wright (Scripps Research Institute, USA)
"Intrinsically disordered proteins"
8:20 pm - 8:35 pm Discussion
8:35 pm - 9:15 pm Lilia Iakoucheva (University of California, San Diego, USA)
"Functions of intrinsically disordered proteins"
9:15 pm - 9:30 pm Discussion
MONDAY
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmCOMPUTATIONAL UNFOLDOMICS: BIOINFORMATICS MEANS FOR IDP DISCOVERY
Discussion Leader: David T. Jones (University College London, UK)
9:00 am - 9:40 am Zsuzsanna Dosztányi (Institute of Enzymology, Budapest, Hungary)
"Predicting intrinsically disordered proteins"
9:40 am - 10:00 am Discussion
10:00 am Coffee Break
10:30 am - 11:10 am Albert Mao (Washington University, St. Louis, USA)
"Polymer physics approach to intrinsic disorder"
11:10 am - 11:30 am Discussion
11:30 am - 12:10 pm Takashi Ishida (Tokyo Institute of Technology, Japan)
"Protein disorder prediction based on the evolutionary conservation"
12:10 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmCOMPUTATIONAL UNFOLDOMICS: FINDING FUNCTIONAL SITES IN IDPs
Discussion Leader: Zoran Obradovic (Temple University, Philadelphia, USA)
7:30 pm - 8:05 pm Christopher J. Oldfield (Indiana University School of Informatics, Indianapolis, USA)
"Coupling folding and binding via MoRFs, molecular recognition features"
8:05 pm - 8:10 pm Discussion
8:10 pm - 8:45 pm Monika Fuxreiter (Institute of Enzymology, Budapest, Hungary)
"Fuzziness of protein-protein interactions"
8:45 pm - 8:50 pm Discussion
8:50 pm - 9:25 pm James Choy (University of West Ontario; London, Ontario, Canada)
"Finding Order in Disorder: Intrinsically Disordered Proteins"
9:25 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmEXPERIMENTAL UNFOLDOMICS: NOVEL INSIGHTS INTO THE IDP STRUCTURE
Discussion Leader: Véronique Receveur-Bréchot (IMR - CNRS, Marseille, France)
9:00 am - 9:40 am Robert (Buzz) Baldwin (Stanford University, USA)
"Desolvation penalty for burying peptide hydrogen bonds"
9:40 am - 9:45 am Discussion
9:45 am - 10:25 am Tanja Mittag (Hospital for Sick Children, Canada)
"Flexibility, compaction, electrostatics: Biophysical basis of the interaction of a polyvalent intrinsically disordered protein"
10:25 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:40 am Cait MacPhee (University of Edinburgh, UK)
"Single molecule studies of intrinsically disordered proteins"
11:40 am - 11:45 am Discussion
11:45 am - 12:25 pm Toshio Ando (Kanazawa University, Japan)
"Visualization of intrinsically disordered regions of proteins by high-speed atomic force microscopy"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmEVOLUTION OF IDPs
Discussion Leader: Celeste Brown (University of Idaho, Moscow, USA)
7:30 pm - 8:10 pm Gary W. Daugdrill (University of South Florida, Tampa, Florida, USA)
"Conservation of dynamic behavior in regions with negligible amino acid sequence conservation"
8:10 pm - 8:30 pm Discussion
8:30 pm - 9:10 pm M. Madan Babu (MRC-Laboratory of Molecular Biology, University of Cambridge, UK)
"Regulation of intrinsically unstructured proteins: from transcript synthesis to protein degradation"
9:10 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmGETTING MORE FROM LESS: FUNCTIONAL DIVERSITY OF IDPs
Discussion Leader: Richard W. Kriwacki (St. Jude Children's Research Hospital, USA)
9:00 am - 9:40 am Dorothy Erie (University of North Carolina, Chapel Hill, North Carolina, USA)
"AFM analysis of conformational changes in MutLα"
9:40 am - 10:00 am Discussion
10:00 am Coffee Break
10:30 am - 11:10 am Martin Weik (IBS (LBM), Grenoble, France)
"Analyzing the dynamics of intrinsically disordered proteins and their hydration water by incoherent neutron scattering"
11:10 am - 11:30 am Discussion
11:30 am - 12:10 pm Vince Hilser (University of Texas Medical Branch, Galveston, Texas, USA)
"Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins"
12:10 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 6:00 pmFree Time
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
(Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair)
7:30 pm - 9:30 pmNATIVE MOLTEN GLUBULES
Discussion Leader: Stefano Ciurli (Science and Technology University of Bologna, Italy)
7:30 pm - 8:10 pm Barbara Zambelli (University of Bologna, Italy)
"UreG as a molten globular enzyme"
8:10 pm - 8:30 pm Discussion
8:30 pm - 9:10 pm Kristiina Mäkinen (University of Helsinki, Finland)
"Native molten globular nature of the Potato virus A genome-linked protein VPg"
9:10 pm - 9:30 pm Discussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmCELLULAR BIOLOGY OF IDPs
Discussion Leader: Peter Tompa (Institute of Enzymology, Hungary)
9:00 am - 9:40 am Ken Nishikawa (Maebashi Institute of Technology, Japan)
"Binary predictor of intrinsic disorder and order"
9:40 am - 9:45 am Discussion
9:45 am - 10:25 am Philipp Selenko (Leibniz Institute of Molecular Pharmacology, Berlin, Germany)
"The structural biology of intrinsically disordered proteins inside living cells"
10:25 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:40 am Michael Rexach (University of California, Santa Cruz, USA)
"Disorder in nuclear pore"
11:40 am - 11:45 am Discussion
11:45 am - 12:25 pm Sara Bondos (Texas A&M Health Science Center, College Station, Texas, USA)
"Interplay between structured and intrinsically disordered regions of Ubx instigates and stabilizes context-specific functions"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 6:00 pmFree Time
6:00 pmDinner
7:30 pm - 9:30 pmINTRINSICALLY DISORDERED PROTEINS AND DISEASE
Discussion Leader: Sonia Longhi (CNRS et Universités d'Aix-Marseille, Marseille, France)
7:30 pm - 8:10 pm David B. Teplow (University of California, UCLA, Los Angeles, California, USA)
"Small peptide, large problems: Aβ and neurodegenerative diseases"
8:10 pm - 8:30 pm Discussion
8:30 pm - 9:10 pm Steven J. Metallo (Georgetown University, Washington, DC, USA)
"Finding inhibitors of protein-protein interactions"
9:10 pm - 9:30 pm Discussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

 
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