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Helical ensembles outperform ideal helices in molecular replacement.

Authors
  • Sánchez Rodríguez, Filomeno1
  • Simpkin, Adam J1
  • Davies, Owen R2
  • Keegan, Ronan M3
  • Rigden, Daniel J1
  • 1 Institute of Structural, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom. , (United Kingdom)
  • 2 Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom. , (United Kingdom)
  • 3 UKRI-STFC, Rutherford Appleton Laboratory, Research Complex at Harwell, Didcot OX11 0FA, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Acta crystallographica. Section D, Structural biology
Publication Date
Oct 01, 2020
Volume
76
Issue
Pt 10
Pages
962–970
Identifiers
DOI: 10.1107/S205979832001133X
PMID: 33021498
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The conventional approach in molecular replacement is the use of a related structure as a search model. However, this is not always possible as the availability of such structures can be scarce for poorly characterized families of proteins. In these cases, alternative approaches can be explored, such as the use of small ideal fragments that share high, albeit local, structural similarity with the unknown protein. Earlier versions of AMPLE enabled the trialling of a library of ideal helices, which worked well for largely helical proteins at suitable resolutions. Here, the performance of libraries of helical ensembles created by clustering helical segments is explored. The impacts of different B-factor treatments and different degrees of structural heterogeneity are explored. A 30% increase in the number of solutions obtained by AMPLE was observed when using this new set of ensembles compared with the performance with ideal helices. The boost in performance was notable across three different fold classes: transmembrane, globular and coiled-coil structures. Furthermore, the increased effectiveness of these ensembles was coupled to a reduction in the time required by AMPLE to reach a solution. AMPLE users can now take full advantage of this new library of search models by activating the `helical ensembles' mode. open access.

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