Bridging the information gap: computational tools for intermediate resolution structure interpretation

Due to large sizes and complex nature, few large macromolecular complexes have been solved to atomic resolution. This has lead to an under-representation of these structures, which are composed of novel and/or homologous folds, in the library of known structures and folds. While it is often difficul...

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Bibliographic Details
Published in:Journal of molecular biology 2001-05, Vol.308 (5), p.1033-1044
Main Authors: Jiang, Wen, Baker, Matthew L., Ludtke, Steven J., Chiu, Wah
Format: Article
Language:English
Subjects:
Algorithms
bioinformatics
Computational Biology - instrumentation
Computational Biology - methods
Computer Simulation
Databases as Topic
electron cryomicroscopy
fold recognition
Internet
macromolecular assemblies
Models, Molecular
Molecular Weight
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins - chemistry
Proteins - metabolism
Software
structure
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Summary:Due to large sizes and complex nature, few large macromolecular complexes have been solved to atomic resolution. This has lead to an under-representation of these structures, which are composed of novel and/or homologous folds, in the library of known structures and folds. While it is often difficult to achieve a high-resolution model for these structures, X-ray crystallography and electron cryomicroscopy are capable of determining structures of large assemblies at low to intermediate resolutions. To aid in the interpretation and analysis of such structures, we have developed two programs: helixhunter and foldhunter. Helixhunter is capable of reliably identifying helix position, orientation and length using a five-dimensional cross-correlation search of a three-dimensional density map followed by feature extraction. Helixhunter’s results can in turn be used to probe a library of secondary structure elements derived from the structures in the Protein Data Bank (PDB). From this analysis, it is then possible to identify potential homologous folds or suggest novel folds based on the arrangement of alpha helix elements, resulting in a structure-based recognition of folds containing alpha helices. Foldhunter uses a six-dimensional cross-correlation search allowing a probe structure to be fitted within a region or component of a target structure. The structural fitting therefore provides a quantitative means to further examine the architecture and organization of large, complex assemblies. These two methods have been successfully tested with simulated structures modeled from the PDB at resolutions between 6 and 12 Å. With the integration of helixhunter and foldhunter into sequence and structural informatics techniques, we have the potential to deduce or confirm known or novel folds in domains or components within large complexes.
ISSN:0022-2836
1089-8638
DOI:10.1006/jmbi.2001.4633