Helical ensembles outperform ideal helices in molecular replacement. Issue 10 (8th October 2020)

• Record Type: Journal Article
• Authors: Sánchez Rodríguez, Filomeno; Simpkin, Adam J.; Davies, Owen R.; Keegan, Ronan M.; Rigden, Daniel J.
• Is Part Of: Acta crystallographica. Volume 76:Issue 10(2020)
• Page Start: 962
• Page End: 970
• Publication Date: 2020-10-08
• Subjects: molecular replacement -- AMPLE -- helical ensembles; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S205979832001133X
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : Helical ensembles solve more structures by MR with AMPLE than do ideal helices and at no greater CPU cost. 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.