On the potential of normal-mode analysis for solving difficult molecular-replacement problems

Karsten Suhre, Yves Henri Sanejouand

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Molecular replacement (MR) is the method of choice for X-ray crystallographic data phasing when structural data of suitable homologues are available. However, MR may fail even in cases of high sequence homology when conformational changes arising for example from ligand binding or different crystallogenic conditions come into play. In this work, the potential of normal-mode analysis as an extension to MR to allow recovery from such drawbacks is demonstrated. Three examples are presented in which screening for MR solutions with templates perturbed in the direction of one or two normal modes allows a valid MR solution to be found where MR using the original template failed to yield a model that could ultimately be refined. It has been shown recently that half of the known protein movements can be modelled by displacing the studied structure using at most two low-frequency normal modes. This suggests that normal-mode analysis has the potential to break tough MR problems in up to 50% of cases. Moreover, even in cases where an MR solution is available, this method can be used to further improve the starting model prior to refinement, eventually reducing the time spent on manual model construction (in particular for low-resolution data sets).

Original languageEnglish
Pages (from-to)796-799
Number of pages4
JournalActa Crystallographica Section D: Biological Crystallography
Volume60
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

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Sequence Homology
X-Rays
Ligands
Proteins
Datasets
Direction compound

ASJC Scopus subject areas

  • Structural Biology
  • Medicine(all)

Cite this

On the potential of normal-mode analysis for solving difficult molecular-replacement problems. / Suhre, Karsten; Sanejouand, Yves Henri.

In: Acta Crystallographica Section D: Biological Crystallography, Vol. 60, No. 4, 04.2004, p. 796-799.

Research output: Contribution to journalArticle

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