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Graph Identification of Proteins in Tomograms (GRIP-Tomo)

Krios Cryogenic Transmission Electron Microscope
Sample being loaded into Aquilos Cryo-Focused Ion Beam/Scanning Electron Microscope
Aquilos Cryo-Focused Ion Beam/Scanning Electron Microscope
round components to Aquilos Cryo-Focused Ion Beam/Scanning Electron Microscope
Samantha Powell stands next to Krios Cryogenic Transmission Electron Microscope

Cryo-electron tomography is an imaging method that reconstructs three-dimensional volumes of cellular ultrastructure, including proteins and other macromolecular complexes. This method holds a great deal of promise for understanding the organization of the native cellular environment and for near-atomic resolution structure determination of individual complexes. However, the required technical imaging parameters occasionally result in data with low contrast (signal to noise ratio) or that are too sparse for scientists to fully determine the structure of a specific target protein.

The Environmental Molecular Sciences Laboratory (EMSL) is developing a capability that will allow scientists to mine data for patterns using the algorithm of graph identification of proteins in tomograms (GRIP-Tomo). The mathematical graphs based on these patterns can identify protein structures from simulated noise-free volume densities of tomograms with high accuracy. EMSL staff scientists are working to adapt and validate the method with real experimental datasets containing low contrast and sparse sampling to understand the range of imaging parameters compatible with GRIP-Tomo for improved protein identification and faster structure determination. While not yet demonstrated, this future implementation of GRIP-Tomo will help scientists develop new biological materials that can be used for clean energy production and other bioproducts. 

EMSL’s GRIP-Tomo will be customizable based on the user’s project needs and is shepherded by EMSL staff scientists in the Systems Modeling Integrated Research Platform (IRP) and Structural Biology IRP. Team members will use EMSL’s mid-range scientific computing resource Tahoma to compare the similarities between graphs from the simulated images and graphs from transformed images taken from samples. This analytical platform will accelerate the mining and interpretation of cryo-electron tomography data and empower a comprehensive modeling of protein complexes in situ.

Research application

Supporting the Systems Modeling Integrated Research Platform (IRP) and the Structural Biology IRP, GRIP-Tomo provides opportunities in integrative structural modeling such as:

  • Megastructures and protein assemblies in situ
  • Multimodal modeling with structural proteomics
  • Systems modeling of protein structures and the phenotypic state of a microbe.

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