Tom Terwilliger: Model-Building Using cryo-EM Maps

Tom Terwilliger, a Los Alamos National Laboratory (LANL) scientist and New Mexico Consortium (NMC) senior scientist, gave a seminar Tuesday March 6, 2018 at the NMC Biolab titled, Model-building using cryo-EM maps.

Tom Terwilliger has helped make macromolecular structure determination by X-ray crystallography easier for generations of scientists by creating easy-to-use tools that automate the entire process. He is a founding member of the Phenix team. Recently he has created Phenix structure determination tools for fully automatic analysis of cryo-EM maps.

Understanding macromolecular structures is very useful and forms a foundation for understanding biology. Usually, these structures are revealed by using X-ray crystallography or cryo-electron microscopy to show a picture of the macromolecule. 

Recent developments in cryo-electron microscopy have spurred a rapid increase in the rate scientists can determine the structure of large molecules. However, model-building at lower resolutions remains challenging due to the lack of detail in the density maps. Cases where both protein and RNA are present and the interpretation of density must include the choice of chain type are also challenging.

Terwilliger and his Phenix team have developed tools for carrying out all the steps necessary for interpreting low-resolution cryo-EM maps. The map-to-model tool chooses optimal map sharpening, divides a map into small contiguous regions of density, builds protein or RNA/DNA into each, optimizes geometry by finding segments that appear to have secondary structure, combines all the models of each chain type together, identifies which chain type fits each part of a map best, and fits all these together into a partial model for the structure.  Any symmetry present in the structure can be included in the model-building process.

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