title: Exploiting subtle structural differences in heavy-atom derivatives for experimental phasing.
abstract: Structure determination using the single isomorphous replacement (SIR) or single-wavelength anomalous diffraction (SAD) methods with weak derivatives remains very challenging. In a recent structure determination of glycoprotein E2 from bovine viral diarrhea virus, three isomorphous uranium-derivative data sets were merged to obtain partially interpretable initial experimental maps. Small differences between them were then exploited by treating them as three independent SAD data sets plus three circular pairwise SIR data sets to improve the experimental maps. Here, how such subtle structural differences were exploited for experimental phasing is described in detail. The basis for why this approach works is also provided: the effective resolution of isomorphous signals between highly isomorphous derivatives is often much higher than the effective resolution of the anomalous signals of individual derivative data sets. Hence, the new phasing approaches outlined here will be generally applicable to structure determinations involving weak derivatives.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Jimin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Yorgo
authors.initials: Y
authors.lastname: Modis
mesh_terms: D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D014759:Viral Envelope Proteins; C076551:gp53, bovine viral diarrhea virus
keywords: data set merging; heavy-atom derivatives; isomorphous replacement; phase combination; phasing; single anomalous dispersion (SAD)