= Ideas for Supplemental Grant =

 * Continue and expand on ChIMP ARRA grant to push forward with visualization of tools for modelling of macromolecular complexes and assemblies.  Specifically:
  1. Add the ability to visualize constraints from multiple sources
  1. Visualize low-resolution structures based on the IMP hierarchical data format
  1. Combine the SAXS tool with normal mode analysis to fit ensembles of structures.
  1. [attachment:IMP_ontology.docx Integrative modeling ontology and user interface].
  1. Other ideas????

 * Remember that none of the items proposed can be funded under the RBVI grant (current or submitted) or the ARRA grant.  This needs to be new work.


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== Combine the SAXS tool with normal mode analysis to fit ensembles of structures ==

Small-angle x-ray scattering (SAXS) is a comparatively simple experimental technique and commonly used for low-resolution structural characterization of molecules in solution (Petoukhov and Svergun, 2007; Schneidman-Duhovny et al., 2010).  SAXS experiment determines the scattering intensity of a molecule as a function of spatial frequency, termed SAXS profile. Although the SAXS profile itself is not enough to determine the accurate molecular structure, it does constrain the possible shapes.  

As updated in the previous report, we had developed an extension to our Chimera visualization package, utilizing our web service, to assess the structural constraints imposed by SAXS data. The extension computes a theoretical SAXS profile for a single molecular model and fits it to the experimental profile displaying the fit graphically. To achieve a better fit, user could either import another structure or manually deform the input molecule. This process is time consuming and less intuitive. It will be more conveniently to take one initial structural model, followed by generating an ensemble of candidate models, finally output the optimal one who has the best fitting with the experimental SAXS. 

The elastic network models (ENMs) (Simonson and Perahia, 1992; Atilgan et al., 2001) are efficient coarse-graining methods, and lend themselves to be the solution of generating ensemble of deformed structures around the input molecule.  The results of ENM are a set of motion vectors and the associated vibration frequencies. Generally, the low-frequency collective motions are involved in biological functions and sampling largest conformation space around the molecular native state.   Taking advantage of recent integration of MMTK with Chimera, which can efficiently generate low-frequency deformations, the Chimera SAXS user will be able to take the results of Chimera-MMTK-ENM as input and send the ensemble of deformed candidate structures to our web server. On the server side, the Fast X-Ray Scattering (FoXS), as another core application of IMP, will calculate SAXS profiles for the ensemble of molecular structures and return the results to Chimera. Results will be shown graphically on both a 2D data fitting plot and Chimera’s main window with the optimal one highlighted.