Workshop on Structural and Computational Proteomics of Biological Complexes

Wah ChiuBaylor College of

Medicine

http://ncmi.bcm.tmc.edu/ncmi/ccbc

• 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 C2BC

"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 200-300 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 selectionSample

purification

Structure analysis

Structure determination

Visualization Archiving

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

C2BC Theme and Policy

• Computational methodology innovations

• Establishing standards• Methodology validation• Cellular validation• Adopting open source policy• Community participation• Enabling tools for biological end-users

C2BC Vision: OrganizationLeadership Team

BiologicalComplexesBiological

Complexes

Structure Determination

Software designand integration

VisualizationStructure Analysis

ArchivingDisseminationand 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 am Ray Jacobson Purification of S. Cerevisiae TFIID for Structural Studies

9:30 am Xiangwei He Molecular architecture of kinetochore in fission yeast

10:00 am Trisha Davis The Lattice Structure of the Yeast Spindle Pole Body Probed by FRET

10:30 am Coffee break

11:00 am Debananda PatiInsights Into Chromosomal Cohesion and Segregation: A Handcuff Model For the Cohesin Complex

11:30 am Frazer Rixon Structural Investigations of HSV Infection

12:00 pm Lunch@ Rice University Faculty Club

Day 1

1:30 pm Ted Wensel Structural Dynamics of Signal-Transducing Membrane Complexes

2:00 pm Mary Porter Structural organization of the I1 inner arm dynein in Chlamydomonas and its implication for the regulation of flagellar motility

2:30 pm Tim Palzkill Systematic Cloning of Bacterial Open Reading Frames for Functional Genomics Studies

3:00 pm Coffee break

3:30 pm Eddy Arnold HIV-1 reverse transcriptase structures: chemistry, biology, and drug design

4:00 pm Wei Wang Computational study of the binding specificities of SH2 and SH3 domains

4:30 pm Orna Resnekov Center for Genomic Experimentation and Computation

5:00 pm Jose Lopez Platelets

Day 1

Day 28:30 am Andrej Sali Modeling the structures of proteins and

macromolecular assemblies

9:00 am Alex Milosavljevic Emerging opportunities at the interface between comparative genomics, genomic resequencing andstructural biology

9:30 am John Markley Sesame: a Data Management System for Structural Proteomics

10:00 am Steve Ludtke EMEN2 - A Distributed Object-oriented ElectronicNotebook for Data Archival, Sharing and Mining

10:30 am Coffee break

11:00 am Zheng Li Modeling Platform for Collaboration

11:30 am Helen Berman Data Management in the Protein Data Bank

12:00 pm Tom Ferrin Enhancing Data Sharing in Collaborative Research Projects with DASH

Day 2

1:30 pm Amy Swain

1:45 pm Wah Chiu Discussion and recommendation

2:30 pm Meeting adjourns