Transcript CHIU_Workshop Intro_05_05_16 - NCMI

Workshop on Structural and
Computational Proteomics
of Biological Complexes
Wah Chiu
Baylor College of
Medicine
http://ncmi.bcm.tmc.edu/ncmi/ccbc
About C2BC
• Focused on the development of computational tools
for studying structures and functions of biological
complexes
• A virtual center of cross-disciplinary and crossinstitutional 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
What is a biological complex (machine)?
"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)
Why Study Large Complexes?
• 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.
Ribosome
Chaperonin: GroEL
Nuclear Pore
Pipeline for Studying Complexes
Sample selection
Structure
analysis
Sample
purification
Structure
determination
Visualization
Archiving
Experimental Challenges
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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
Computational Challenges
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No defined ontology
Distributed, heterogeneous data
Large data sets
Multiple conformational states
Data processing techniques
Archival of complexes
Complex visualization
Specialized software
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: Organization
Leadership Team
Structure
Determination
Visualization
Structure
Analysis
Biological
Complexes
Archiving
Software design
and integration
Dissemination
and training
Workshop Goals
• 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 interdisciplinary data exchange
Day 1
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
Day 1
1:30 pm
Ted Wensel
2:00 pm
Mary Porter
2:30 pm
Tim Palzkill
3:00 pm
Coffee break
3:30 pm
Eddy Arnold
4:00 pm
4:30 pm
5:00 pm
Structural Dynamics of Signal-Transducing
Membrane Complexes
Structural organization of the I1 inner arm
dynein in Chlamydomonas and its implication
for the regulation of flagellar motility
Systematic Cloning of Bacterial Open Reading
Frames for Functional Genomics Studies
HIV-1 reverse transcriptase structures:
chemistry, biology, and drug design
Wei Wang
Computational study of the binding specificities
of SH2 and SH3 domains
Orna Resnekov Center for Genomic Experimentation and
Computation
Jose Lopez
Platelets
Day 2
8:30 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 and
structural biology
9:30 am John Markley
Sesame: a Data Management System for
Structural Proteomics
10:00 am Steve Ludtke
EMEN2 - A Distributed Object-oriented Electronic
Notebook 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
2:30 pm
Meeting adjourns
Discussion and
recommendation