Fast 3D motif search of EM density maps using a locally normalized cross-correlation function

Three-dimensional motif search is becoming increasingly important both in the search for molecular signatures within a tomographic reconstruction, at low resolution, and in the search for atomic structures within high-resolution cryo-EM maps of macromolecular complexes. The present work describes the implementation of a fast local correlation algorithm suitable for template matching in the SPIDER environment. Two examples are given, one in each of the areas of application: (i). within a 7.8A single-particle reconstruction of the Escherichia coli ribosome, four proteins and one RNA structure were located with high accuracy; (ii). within a cryo-tomogram of sarcoplasmic reticulum vesicles, ryanodine receptors were located in positions that agreed with expert knowledge.