The advent of the direct detector camera and other related technologies has produced rapid growth in the field of cryogenic electron microscopy (cryo-EM), resulting in large numbers of new cryo-EM 3-D reconstructions and a high demand for atomistic models corresponding to these reconstructions. Currently, most models are constructed with manual intervention; however, with multiple conformations existing for each complex and with a large number of new groups entering the field, we anticipate growth in the demand for automated construction of models. Here, we present cryo_fit, a module in the PHENIX structural biology package that includes automated fitting for high-resolution cryo-EM data sets, producing all-atom models consistent with the EM density. Using a molecular dynamics approach, atomic positions are optimized with a potential that includes the cross-correlation coefficient between the structural model and the cryo-EM electron density, as well as a biasing potential preserving the stereochemistry and secondary structure of the biomolecule. Specifically, we use a hybrid structure-based/ab initio molecular dynamics potential to extend molecular dynamics fitting.1 We obtain atomistic models of the human ribosome consistent with high-resolution cryo-EM reconstructions of the human ribosome. We designed the module to automate the multiple steps of MD simulation and keep record of input commands and files for reproduction and management, as well as facilitating refinement and validation through PHENIX. We aim for scientists with no experience in MD simulation to produce high quality automated models.

CryoFIT: User-friendly fitting of high-resolution cryo-EM reconstructions in PHENIX

2019 Spring National Meeting

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