Automation and assessment of de novo modeling with Pathwalking in near atomic resolution cryoEM density maps.
J Struct Biol
; 204(3): 555-563, 2018 12.
Article
in En
| MEDLINE
| ID: mdl-30237066
ABSTRACT
With the rapidly growing number of macromolecular structures solved to near-atomic resolution using electron cryomicroscopy (cryoEM), map interpretation and model building directly from the density without the use of structural templates has become increasingly important. As part of the 2015/2016 Map and Model Challenge, we attempted to assess our latest de novo modeling tool, Pathwalking, in terms of performance and usability, as well as identify areas for future improvements. In total, we applied Pathwalking to six density maps between 3 and 4.5â¯Å resolution selected from the challenge data sets. In five of the six cases, Pathwalking was able to accurately determine the protein fold and in three of these cases, the final all atom model had less than 1.6â¯Å RMSD when compared to the known structure. Model building and refinement was nearly completely automated, used default parameters and took less than 30â¯min to complete a refined all atom model. A direct outgrowth of this work was a more streamlined automated command line Pathwalking utility, as well as a novel sequence assignment and optimization routine, which attempts to register sidechain density with expected side chain volume. In total, Pathwalking offers a nearly complete, robust and efficient method for constructing atomistic protein structures directly from a density map without the aid of a template.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Conformation
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Automation
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Algorithms
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Proteins
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Cryoelectron Microscopy
Language:
En
Journal:
J Struct Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2018
Type:
Article
Affiliation country:
United States