Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EM.

Florence Tama; Osamu Miyashita; Charles L Brooks

doi:10.1016/j.jsb.2004.03.002

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Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EM.

Florence Tama·Osamu Miyashita·Charles L Brooks

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Abstract

A new method for the flexible fitting of high-resolution structures into low-resolution maps of macromolecular complexes from electron microscopy has been recently described in applications to simulated electron density maps. This method uses a linear combination of low-frequency normal modes in an iterative manner to deform the structure optimally to conform to the low-resolution electron density map. Gradient-following techniques in the coordinate space of collective normal modes are used to optimize the overall correlation coefficient between computed and measured electron densities. With this approach, multi-scale flexible fitting can be performed using all-atoms or Calpha atoms. In this paper, illustrative studies of normal mode based flexible fitting to experimental cryo-EM maps are presented for three different systems. Large, functionally relevant conformational changes for elongation factor G bound to the ribosome, Escherichia coli RNA polymerase and cowpea chlorotic mottle virus are elucidated as the result of the application of NMFF from high-resolution structures to cryo-electron microscopy maps.

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Cryoelectron Microscopy DNA-Directed RNA Polymerases Escherichia coli Models, Molecular Models, Theoretical Peptide Elongation Factor G Protein Conformation Sensitivity and Specificity Comparative Study Journal Article Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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Florence Tama, Osamu Miyashita, Charles L Brooks. 2004. Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EM.. https://doi.org/10.1016/j.jsb.2004.03.002

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