Research projects under the MMTSB Core are
guided, extended and complemented by our ongoing Collaborative Research
Efforts. Throughout the course of our resource activities collaborative projects
finish and new ones are initiated. Scientists interested in becoming involved in collaborative
projects with MMTSB scientists are encouraged to contact an MMTSB Center investigator.
Current collaborative projects include:
- Modeling ribosomal particles from E. coli
This will focus our development efforts
in this area on important experimental systems and provide the opportunity
for input on software development from a key player in nucleic acid
structure and function. Dr Frank has collaborated with two of our resource
scientists in the past and his continued involvement will help us keep
abreast of the most timely issues in modeling these large composite
particles (Projects IV and V).
- Investigations of the assembly dynamics and energetics of
ribosomal particles and RNA through collaborative efforts with
and Joachim Frank.
These collaborative investigators bring extensive experience in exploring the assembly
of the 30S ribosomal particle and issues of RNA folding, RNA secondary structure formation, molecular
electrostatic interactions in large molecular assemblies and ribosome structure and functional dynamics,
respectively. These collaborative projects will interface with Projects I and IV.
- Investigation of the structure and dynamics of eukaryotic chromosomes in vivo,
in collaboration with Job Dekker
of the University of Massachusetts. Dekker's laboratory has developed chemical
cross-linking methods that reveal the relative contact frequencies of different regions of the chromosome.
Their initial data were consistent with an analytical model that treated the entire chromosome as an elastic polymer
with a uniform persistence length, but more extensive data have revealed regions of different flexibilities, requiring
more complex computational models.
- Additional focus on model building, refinement and functional rearrangement of
large systems associated with biologically important macromolecular assemblies (myosin, anthrax,
chaperons (GroEL), large enzymes (gutamate dehydrogenase), and the phi29 connector associated
with DNA packaging) will be provided through our collaborations with
and Ed Gogol,
Tom Smith and
Jiali Gao, respectively. Each of these scientists is a leading
expert in the structure
and function of the molecular assemblies noted and their involvement as collaborators will significantly assist
our refinement of the tools developed in Projects IV and V.
- Extending the range of approaches used to explore virus assembly and the continued
exploration of the mechanical properties of virus capsids will be achieved through collaborative efforts with
Robijn Bruinsma and
Rob Phillips. Collaborative projects with this group of scientists will
assist our Core efforts in the development of simple physical models for the assembly of virus capsids and the structural and
mechanical properties of assembled virus particles (Project III).
- Establishing new and strong links between MMTSB and the Research Collaboratory for Structural
Bioinformatics (RCSB/PDB) in the area of virus structure and analysis will be a key emphasis. In a collaborative effort with
MMTSB and the VIPER web-base will become an integrated component of the PDB.
- Explorations of RNA packaging in virus capsids using multi-resolution RNA models will be
driven by collaborative efforts between two resource PIs (Johnson and Harvey) through Core Projects I, III and independent
funding recently acquired by RR PI to investigate DNA and RNA packaging (Harvey).
- Advances in visualization of virus particles and their constituent molecular components will
enhance our continued development of the VIPER web-base and be afforded through collaborative efforts with
Chandrajit Bajaj from
Center for Computational Visualization,
University of Texas, Austin, Texas. Additionally, interactions with
Manjunath Kini will explore protein-protein interactions within virus capsids. These collaborations will strengthen the software integration core (Project V) as well as our
dissemination and web presence for the VIPER site.
- Furthering the interdigitation between the Core Projects, collaborative efforts with
Shuang Huang will
explore emerging bioinformatics regarding virus sequence/structure/assembly relationships and structural
modeling associated with the engineering of surface epitope loops to explore the display of the antigenic
epitopes to prime the immune system against the known pathogens and toxins. This collaborative component
will interface with Projects II and III.
- Extending the functionality of our structure and modeling tools and structure prediction
infrastructure through collaborations with former MMTSB scientist
Michael Feig and with the developer and project
leader of the BOINC team at Berkeley,
The Feig collaboration will focus on extension of the
MMTSB Tool Set to include enhanced functionality for nucleic acids as well as implementation of a molecular
dynamics repository and analysis facility. Work with the BOINC (Berkeley Open Infrastructure for Network Computing)
team will strengthen the structure prediction infrastructure utilized recently in CASP6, and its further development as
part of our structure prediction and multi-scale sampling Core Project (II).
- Exploit recent MMTSB RR developments in the areas of solvation models, including implicit
solvent/implicit membrane generalized Born models, and advanced sampling methods, like the replica-exchange molecular
dynamics methods integrated into the MMTSB Tool Set, to address key issues in the de novo structure determination of proteins in
solution and membrane protein insertion and folding, through collaborations with
Jane Dyson and
Steve White, and in partially (or fully) ordered environments with
Stanley Opella, the directory of the NIBIB
Center for NMR Spectroscopy and Imaging of Proteins.
Through these collaborations we will harden the methods and models developed as components of Projects I and II.
- Develop new and perptuate existing collaborative efforts to organize training and research workshops
with neighboring centers including the CTBP directed by
overseen by Bridget Carragher and
Clint Potter and the
Pittsburgh Super Computing Center.