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PDBsum entry 4c4z
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References listed in PDB file
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Key reference
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Title
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A combination of spin diffusion methods for the determination of protein-Ligand complex structural ensembles.
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Authors
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J.Pilger,
A.Mazur,
P.Monecke,
H.Schreuder,
B.Elshorst,
S.Bartoschek,
T.Langer,
A.Schiffer,
I.Krimm,
M.Wegstroth,
D.Lee,
G.Hessler,
K.U.Wendt,
S.Becker,
C.Griesinger.
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Ref.
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Angew Chem Int Ed Engl, 2015,
54,
6511-6515.
[DOI no: ]
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PubMed id
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Abstract
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Structure-based drug design (SBDD) is a powerful and widely used approach to
optimize affinity of drug candidates. With the recently introduced INPHARMA
method, the binding mode of small molecules to their protein target can be
characterized even if no spectroscopic information about the protein is known.
Here, we show that the combination of the spin-diffusion-based NMR methods
INPHARMA, trNOE, and STD results in an accurate scoring function for docking
modes and therefore determination of protein-ligand complex structures.
Applications are shown on the model system protein kinase A and the drug
targets glycogen phosphorylase and soluble epoxide hydrolase (sEH). Multiplexing
of several ligands improves the reliability of the scoring function further. The
new score allows in the case of sEH detecting two binding modes of the ligand in
its binding site, which was corroborated by X-ray analysis.
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