Segmentation and registration of molecular components in 3-dimensional density maps from cryo-electron microscopy
Name
631235678-MIT.pdf
Description
Full printable version
Size
72.42 MB
Format
Adobe PDF
Checksum (MD5)
4881f766bf23e29ef233d1fe2b34964a
Author(s)
Pintilie, Grigore Dimitrie, 1976-
Advisor(s)
David C. Gossard.
Date Issued
2010
Publisher
Massachusetts Institute of Technology
Abstract
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.
(cont.) The registrations are refined using a gradient-based method, which locally optimizes the density cross-correlation score. A search algorithm is presented for automatically finding groups of regions that produce correct registrations. The accuracy of these registration methods is measured using simulated density maps, and then the methods are used to register structures of individual proteins and subunits with density maps obtained by cryo-electron microscopy.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2010.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis.
Includes bibliographical references (p. 89-93).
Subjects
Electrical Engineering and Computer Science.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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