Heterogeneity of large macromolecular complexes revealed by 3D cryo-EM variance analysis.

ABSTRACT: Macromolecular structure determination by cryo-electron microscopy (EM) and single-particle analysis are based on the assumption that imaged molecules have identical structure. With the increased size of processed data sets, it becomes apparent that many complexes coexist in a mixture of conformational states or contain flexible regions. We describe an implementation of the bootstrap resampling technique that yields estimates of voxel-by-voxel variance of a structure reconstructed from the set of its projections. We introduce a highly efficient reconstruction algorithm that is based on direct Fourier inversion and that incorporates correction for the transfer function of the microscope, thus extending the resolution limits of variance estimation. We also describe a validation method to det

SUBMITTER: Zhang W 

PROVIDER: S-EPMC2642923 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature