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PDBsum entry 3nk8
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References listed in PDB file
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Key reference
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Title
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Combined use of computational chemistry, Nmr screening, And X-Ray crystallography for identification and characterization of fluorophilic protein environments.
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Authors
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A.Vulpetti,
N.Schiering,
C.Dalvit.
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Ref.
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Proteins, 2010,
78,
3281-3291.
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PubMed id
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Abstract
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(19)F NMR screening of fluorinated fragments with different Local Environment of
Fluorine, a.k.a. LEF library, is an experimental methodology which, beyond
providing useful starting fragments for fragment-based drug discovery projects,
offers, in combination with crystal and computational analysis, an approach for
the identification of fluorophilic hot-spots in the proteins of interest. The
application of this approach in the identification of fluorinated fragments
binding to the serine protease trypsin, and the X-ray structures of the
complexes are presented. The specific nature of the observed fluorine-protein
interactions is discussed and compared with the interactions detected for other
fluorinated ligands reported in the protein data bank. The presence of similar
3D arrangements of protein atoms at the fluorine sub-sites is identified with a
newly developed tool. In this approach, protein sub-sites are extracted around
each fluorine contained in the protein data bank and compared with the query of
interest by using a pharmacophoric description.
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