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@ARTICLE{Schrder:9741,
author = {Schröder, G.F. and Levitt, M. and Brunger, A.T.},
title = {{S}uper-resolution biomolecular crystallography with
low-resolution data},
journal = {Nature},
volume = {464},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publising Group},
reportid = {PreJuSER-9741},
pages = {1218 - 1222},
year = {2010},
note = {We thank P. D. Adams, S. C. Harrison and T. D. Fenn for
discussions. We also thank the National Science Foundation
for computing resources (CNS-0619926), the National
Institutes of Health for both Roadmap Grant PN2 (EY016525)
and grant GM63718 to M. L., and the Deutsche
Forschungsgemeinschaft (DFG) for support for G. F. S.},
abstract = {X-ray diffraction plays a pivotal role in the understanding
of biological systems by revealing atomic structures of
proteins, nucleic acids and their complexes, with much
recent interest in very large assemblies like the ribosome.
As crystals of such large assemblies often diffract weakly
(resolution worse than 4 A), we need methods that work at
such low resolution. In macromolecular assemblies, some of
the components may be known at high resolution, whereas
others are unknown: current refinement methods fail as they
require a high-resolution starting structure for the entire
complex. Determining the structure of such complexes, which
are often of key biological importance, should be possible
in principle as the number of independent diffraction
intensities at a resolution better than 5 A generally
exceeds the number of degrees of freedom. Here we introduce
a method that adds specific information from known
homologous structures but allows global and local
deformations of these homology models. Our approach uses the
observation that local protein structure tends to be
conserved as sequence and function evolve. Cross-validation
with R(free) (the free R-factor) determines the optimum
deformation and influence of the homology model. For test
cases at 3.5-5 A resolution with known structures at high
resolution, our method gives significant improvements over
conventional refinement in the model as monitored by
coordinate accuracy, the definition of secondary structure
and the quality of electron density maps. For re-refinements
of a representative set of 19 low-resolution crystal
structures from the Protein Data Bank, we find similar
improvements. Thus, a structure derived from low-resolution
diffraction data can have quality similar to a
high-resolution structure. Our method is applicable to the
study of weakly diffracting crystals using X-ray
micro-diffraction as well as data from new X-ray light
sources. Use of homology information is not restricted to
X-ray crystallography and cryo-electron microscopy: as
optical imaging advances to subnanometre resolution, it can
use similar tools.},
keywords = {Crystallization / Crystallography, X-Ray: methods /
Databases, Protein / Electrons / Likelihood Functions /
Models, Molecular / Oligopeptides: chemistry / Protein
Conformation / Software / Static Electricity / Oligopeptides
(NLM Chemicals) / J (WoSType)},
cin = {ISB-3},
ddc = {070},
cid = {I:(DE-Juel1)VDB942},
pnm = {Funktion und Dysfunktion des Nervensystems / BioSoft:
Makromolekulare Systeme und biologische
Informationsverarbeitung},
pid = {G:(DE-Juel1)FUEK409 / G:(DE-Juel1)FUEK505},
shelfmark = {Multidisciplinary Sciences},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:20376006},
pmc = {pmc:PMC2859093},
UT = {WOS:000276891100043},
doi = {10.1038/nature08892},
url = {https://juser.fz-juelich.de/record/9741},
}