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PDBsum entry 5p5o
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References listed in PDB file
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Key reference
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Title
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High-Throughput crystallography: reliable and efficient identification of fragment hits.
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Authors
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J.Schiebel,
S.G.Krimmer,
K.Röwer,
A.Knörlein,
X.Wang,
A.Y.Park,
M.Stieler,
F.R.Ehrmann,
K.Fu,
N.Radeva,
M.Krug,
F.U.Huschmann,
S.Glöckner,
M.S.Weiss,
U.Mueller,
G.Klebe,
A.Heine.
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Ref.
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Structure, 2016,
24,
1398-1409.
[DOI no: ]
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PubMed id
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Abstract
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Today the identification of lead structures for drug development often starts
from small fragment-like molecules raising the chances to find compounds that
successfully pass clinical trials. At the heart of the screening for fragments
binding to a specific target, crystallography delivers structural information
essential for subsequent drug design. While it is common to search for bound
ligands in electron densities calculated directly after an initial refinement
cycle, we raise the important question whether this strategy is viable for
fragments characterized by low affinities. Here, we describe and provide a
collection of high-quality diffraction data obtained from 364 protein crystals
treated with diverse fragments. Subsequent data analysis showed that ∼25% of
all hits would have been missed without further refining the resulting
structures. To enable fast and reliable hit identification, we have designed an
automated refinement pipeline that will inspire the development of optimized
tools facilitating the successful application of fragment-based methods.
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