Workshop on Structural and Computational Proteomics of Biological Complexes

Wah Chiu Baylor College of Medicine

Focused on the development of computational tools for studying structures and functions of biological complexes A virtual center of cross-disciplinary and cross- institutional research Bring together investigators from diverse disciplines including crystallography, electron cryomicroscopy, mass spectroscopy, bioinformatics, cell biology, biochemistry, genetics, virology, system biology, clinical medicine, computational science, computer science and software engineering About C 2 BC

"We have always underestimated cells. … The entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines. … Why do we call the large protein assemblies that underlie cell function protein machines? Precisely because, like machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts.“ (Bruce Alberts, "The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists," Cell, 92: 291, 1998) What is a biological complex (machine)?

Proteins typically function in association with other proteins. Protein complexes are important for virtually every biological process and most diseases. Genome sequences identify tens of thousands of genes: linking these to core biological processes will make their study manageable. Recently developed and/or improved technologies and methodologies make studies of large complexes more feasible and informative. Why Study Large Complexes?

Ribosome

Chaperonin: GroEL

Nuclear Pore

Sample selection Sample purification Structure analysis Structure determination VisualizationArchiving Pipeline for Studying Complexes

Identification of complexes Purification of complexes Sample quantity/concentration Sample solubility Heterogeneous samples Multiple functional states Structural solutions of conformationally heterogeneous samples Validation of complexes in the living cell Experimental Challenges

No defined ontology Distributed, heterogeneous data Large data sets Multiple conformational states Data processing techniques Archival of complexes Complex visualization Specialized software Computational Challenges

C 2 BC Theme and Policy Computational methodology innovations Establishing standards Methodology validation Cellular validation Adopting open source policy Community participation Enabling tools for biological end-users

C 2 BC Vision: Organization Leadership Team Biological Complexes Biological Complexes Structure Determination Software design and integration Visualization Structure Analysis Archiving Dissemination and training

Discuss recent developments in the study of large biological complexes Engage the participants in discussing the future directions of structural studies of large complexes Identify and address present and future problems in such studies Search for a common framework for inter- disciplinary data exchange Workshop Goals

8:30 am Wah Chiu Welcome remarks and agenda 9:00 amRay JacobsonPurification of S. Cerevisiae TFIID for Structural Studies 9:30 amXiangwei HeMolecular architecture of kinetochore in fission yeast 10:00 am Trisha DavisThe Lattice Structure of the Yeast Spindle Pole Body Probed by FRET 10:30 am Coffee break 11:00 amDebananda PatiInsights Into Chromosomal Cohesion and Segregation: A Handcuff Model For the Cohesin Complex 11:30 amFrazer Rixon Structural Investigations of HSV Infection 12:00 Rice University Faculty Club Day 1

1:30 pmTed WenselStructural Dynamics of Signal-Transducing Membrane Complexes 2:00 pm Mary PorterStructural organization of the I1 inner arm dynein in Chlamydomonas and its implication for the regulation of flagellar motility 2:30 pm Tim PalzkillSystematic Cloning of Bacterial Open Reading Frames for Functional Genomics Studies 3:00 pmCoffee break 3:30 pmEddy ArnoldHIV-1 reverse transcriptase structures: chemistry, biology, and drug design 4:00 pmWei WangComputational study of the binding specificities of SH2 and SH3 domains 4:30 pmOrna ResnekovCenter for Genomic Experimentation and Computation 5:00 pmJose LopezPlatelets Day 1

Day 2 8:30 amAndrej SaliModeling the structures of proteins and macromolecular assemblies 9:00 amAlex MilosavljevicEmerging opportunities at the interface between comparative genomics, genomic resequencing and structural biology 9:30 amJohn MarkleySesame: a Data Management System for Structural Proteomics 10:00 am Steve LudtkeEMEN2 - A Distributed Object-oriented Electronic Notebook for Data Archival, Sharing and Mining 10:30 amCoffee break 11:00 am Zheng LiModeling Platform for Collaboration 11:30 am Helen BermanData Management in the Protein Data Bank 12:00 pmTom FerrinEnhancing Data Sharing in Collaborative Research Projects with DASH

Day 2 1:30 pmAmy Swain 1:45 pmWah ChiuDiscussion and recommendation 2:30 pmMeeting adjourns