Segmentation and registration of molecular components in 3-dimensional density maps from cryo-electron microscopy

Cryo-electron microscopy is a method that produces 3D density maps of macromolecular complexes. Segmentation and registration methods are heavily used to extract structural information from such density maps. Segmentation aims to identify regions in a density map corresponding to individual molecular components, so as to allow us to understand their complex arrangements and the relation of these arrangements to the function of the complex. Currently used segmentation methods rely to a large degree upon user interaction and thus are tedious and yield subjective results. We present a multi-scale segmentation method requiring very little interaction and guidance from the user. The segmentation accuracy of this method is quantified for simulated density maps, using a shape-based metric. The method is applied to several density maps of various sizes and complexity, producing accurate results. Registration of molecular structures with density maps helps to relate the vast structural information from X-ray crystallography with the structural information contained in cryo-electron microscopy density maps. The most reliable registration methods to date depend on exhaustive search, which is time-intensive and scales poorly with map and structure size. Two methods are presented that achieve direct registration of structures with density maps, based on the alignment of the structures to segmented regions.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Pintilie, Grigore Dimitrie, 1976-

Advisor dc:contributor.advisor

• David C. Gossard.

• Electrical Engineering and Computer Science.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/57536

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/57536