Ideas and discussions for the RBVI 2011 Site Visit

Scenarios

Scenario 1

• SFLD/Cytoscape/Chimera
• (Scenario #1 from 2009 Advisory Committee mtg: ​https://plato.cgl.ucsf.edu/trac/SFLD/wiki/RBVIAdvisoryCommitteeMeeting#no1)

Scenario 2

• Chimera/Volume Tools/Cytoscape(?)
• (Scenario #2 from 2009 Advisory Committee mtg: ​https://plato.cgl.ucsf.edu/trac/chimera/wiki/HIVspikes)

Ideas of what to show

TR&D 1

• BLAST service
• Modeller interface
• useful chain information now appears in status upon mouseover in graphics window
• multiple alignment from source other than BLAST if we want to make statements about conservation, perhaps with corresponding tree (for example, domain family seed alignments + trees can be obtained from Pfam; for 2009 we got seqs from HIV database; SFLD alignments another good possibility)
• alignment Conservation header (sequence conservation, AL2CO options include entropy, variability, etc.)
• alignment RMSD header (spatial conservation of associated superimposed structures)
• custom header (used in 2009 hivspikes demo to show importance for antibody binding, probably not time for it this year)
• render by attribute (could be attribute from MAV header or other such as bfactor or Modeller error profile)
• Uniprot annotations on sequence either from direct Uniprot fetch of sequence or from using PDB/UniProt Info tool (good for showing relationship of gp120 core constructs in which loops had been replaced with stubs to the full-length sequence... unfortunately PDB SIFTS service has a data problem with 1GC1 but 1G9M is nearly identical and could be used instead)
• other fetch by ID (EMDB, PubChem, ...) and caching
• a time-saving suggestion is to put aliases in a startup (.midasrc) file, then without having to use a previously saved session it is easy to do something to predefined sets of residues, e.g. "color red epitope1"
• Profilegrid (existing standalone, allows presenting some future plans; downside is that it is probably hard to see and understand up on a projected screen)
• superposition
• find clashes and/or H-bonds
• morphing was shown last site visit
• flying through positions or scenes? are we going to do anything about presentation tools other than Tom's web log?

TR&D 2

These are the 4 areas mentioned in the core 2 proposal in the order I would say is most interesting to least interesting.

• Building a "composite model" and linking molecules, maps and sequences of components.
• Chimera analysis web log. Would be cool to demo WebGL embedded in Chimera log then shown on a smart phone or tablet as a way to facilitate hallway/lecture-hall/lunch collaborative work.
• Segmentation of tomography or single particle maps, Segger.
• Fitting in EM maps.

Biological Systems

Alpha Crystallin

• ​Alpha Crystallin - Already prepared multifaceted demo including BLAST, homology modeling, crystal unit cell, EM fitting, and SAXS, for Gordon conf but cut due to time limits. Connected to heart disease, cataracts and amyloid aggregation diseases.
• Clathrin cage tomography from Yifan Cheng. Similar to alpha crystallin cages. Could demo Segger segmentation and proposed tomogram filtering.

HIV Capsid

• ​HIV Capsid - Illustrates composite model building of HIV conical core particle. Capsid protein interfaces highly conserved drug target (June 2011 PNAS ​paper)
• ​Rous sarcoma virus - Retrovirus with very similar capsid to HIV. Did EM fitting and comparison to HIV at EMAN 2011 workshop. 50 minute ​video.
• ​HIV RNA - Secondary structure of full HIV RNA, I made 3-d model and animation with Chimera script. Nature 2009 ​paper). Might add nucleocapsid protein tightly packed on RNA, and collapse RNA into capsid.
• ​Dengue virus - Maturation of dengue virus involves major rearchitecting of capsid. Chimera animation shows hypothetical model from Michael Rossmann lab.

Others

• ​Termite gut - Segmentation tool demo.
• ​Muscle filaments, myosin / actin / tropomyosin. Another good "composite" model example. Haven't done much with this system yet though. Recent Roger Craig / Raul Padron ​paper, PNAS July 2011
• influenza virus - electron tomography of viral particles; recently discovered broadly neutralizing Abs, crystal structures of these bound to hemagglutinin, 2 papers and Perspective article in ​Science 12 Aug 2011 issue; EM/fitting work on RNPs (the stuff inside the capsid)

TR&D 3

TR&D 4

• StructureViz -- linking Cytoscape and Chimera
• clusterMaker
• Incremental loading of networks
• Fuzzy clusters (?)
• Invoking Cytoscape from Chimera
• SFLDLoader2??