= ChimeraX Grant Funding Specific Aims =

October 21, 2021

== [https://www.rbvi.ucsf.edu/chimerax/data/grant-plans-oct2021/R01_2017.pdf R01 2018-2022] - ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale Modeling (NIH Reporter) ==

* Aim 1: Continue the design, implementation, documentation and dissemination of ChimeraX for the interactive visualization and analysis of atomic and cryo-electron microscopy data sets.  In our vision for a multi-scale modeling environment, ChimeraX is the molecular visualization and analysis component that provides integrated interactive tools for analyzing a variety of data types that vary in scale from atomic structures to cryo-EM density maps to large molecular complexes such as the nuclear pore.
  - Aim 1A: Further strengthen ChimeraX’s ability to efficiently read, display and manipulate very large homogeneous and heterogeneous data sets.
  - Aim 1B: Integrate two-dimensional diagrams with the three-dimensional graphics for linking non-spatial data with molecular visualization.
  - Aim 1C: Implement novel analysis and modeling functionality and user interfaces, integrate existing web resources, and migrate selected Chimera tools to ChimeraX.
  - Aim 1D: Create an export mechanism to facilitate disseminating results and hypotheses generated in ChimeraX via a WebGL-based viewer.
* Aim 2: Within the ChimeraX framework, develop tools for atomic-resolution modeling from cryo-electron microscopy data sets. Develop software for visualization, modeling, validation and analysis of molecular assemblies imaged with state-of-the-art cryo-EM, especially at atomic resolutions (2-4Å).
  - Aim 2A: Develop analyses of map quality for model building. Calculate and show spatial variations in resolution, find domain motions, identify and quantify approximate symmetries, analyze difference maps, perform segmentation.
  - Aim 2B: Create interactive model building and measurement tools. Locate template structures from within the PDB, calculate domain and secondary structure motions for optimal fits, utilize de novo backbone tracing algorithms.  Compare related models with real-time animation of conformational changes. Measure motions, distances, variation in contact areas, and create schematic 2D and 3D illustrations of measured quantities.
  - Aim 2C: Devise new model validation tools, including atomic model validation, comparing models to maps, detecting atomic clashes and unfavorable geometries, manually correcting problems, and launching automated refinement methods. Highlight conformational and sequence differences in models derived from different experimental conditions or mutants.
* Aim 3: Design, implement and document software interfaces to facilitate community development of new algorithms and methods by building upon the ChimeraX platform.  Community development has proven to be a very successful paradigm for our older Chimera application.  The goal of this aim is to ensure that ChimeraX will also provide a highly attractive visualization and analysis infrastructure for the development of novel algorithms and tools by others.
  - Aim 3A: Create and document semantically versioned application programming interfaces (API) for ChimeraX libraries.
  - Aim 3B: Design and implement a mechanism for interactive installation of new tools and updates to existing tools in ChimeraX from an RBVI-provided repository accessible via the Web.
  - Aim 3C: Create a Web interface for external developers to deposit and distribute their tools using the RBVI repository.

== [https://www.rbvi.ucsf.edu/chimerax/data/grant-plans-oct2021/NIAID_2021.pdf NIAID contract, Feb 2021 - Feb 2022] - NIH 3D pipeline, Multi-person VR, HuBMAP, Segmentation, DICOM, Outreach. ==

* General ChimeraX improvements to support NIAID (Eric: 20%)
* Support the NIH 3D pipeline development, including any changes to ChimeraX to support ongoing development. (Eric: 15%)
* Improve multi-person VR (Tom: 35%)
  - Create video tutorials in how to use multi-person VR
  - Hold VR office hours to train researchers to use VR capabilities
  - Allow participants to add models from local files during a VR session
  - Set up VR meeting servers for Africa, Europe, Asia
* Human Biomolecular Atlas Program (HuBMAP) multiscale visualization (Eric: 30%)
  - Develop ChimeraX tool to browse and select HuBMAP datasets for loading
* Enhance ChimeraX’s segmentation capabilities
  - Investigate increased use of simple ITK to support segmentation (Tom: 15%)
  - Investigate utilizing web services to support more complex machine learning-based segmentation algorithms (Tom: 15%)
  - Investigate reading and displaying segmentation format(s) available from imaging databases (tissue microscopy, cancer imaging data, etc.) (Tom: 10%)
* DICOM (Tom: 25%, Eric: 5%)
  - Improve ability to visualize and analyze medical images in VR with ChimeraX
  - Develop browser-style interface to show DICOM dataset contents and associated metadata such as sample characteristics
* Outreach
  - Instructional material and tools documentation. (20%)
    * Detailed instructions for all features shall be provided in a user manual
    * Written user guides and tutorials shall be available as an HTML page
* Administration (10%)
  - Submit monthly written reports of accomplishments

== [https://www.rbvi.ucsf.edu/chimerax/data/grant-plans-oct2021/Phenix_R24_2021.pdf Phenix R24 2021-2026] - Phenix interaction with ChimeraX ==

* Implement ChimeraX/Phenix communication APIs.
* Implement fragment extension ChimeraX user interface.
* Implement ligand placement ChimeraX user interface.
* Implement restraint specification ChimeraX user interface.
* Implement validation ChimeraX user interface.

== [https://www.rbvi.ucsf.edu/chimerax/data/grant-plans-oct2021/CZI_EOSS_2021.pdf CZI Essential Open Source Software 2021-2023] - Molecular Visualization: Transitioning Chimera to ChimeraX ==

* Export Chimera sessions to ChimeraX.
* Port multiple sequence alignment and homology modeling web services.
* Update the Qt window toolkit from version 5 to 6.
* Replace OpenGL graphics with Vulkan.
* Distribute a native ChimeraX for Mac ARM CPUs.
* Develop a PyPi library to distribute non-UI components of ChimeraX.

== [https://www.rbvi.ucsf.edu/chimerax/data/grant-plans-oct2021/R01_2021.pdf R01 2022-2026] - proposed renewal ==