Tools for fragment based drug discovery

Structure Elucidation

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STRUCTURE ELUCIDATION


ZoBio has pioneered an approach that is general, efficient and can be applied to reasonably large targets up to 45 – 50 kDa to obtain high resolution structures of ligand-target complexes by NMR (Shah, J. Med. Chem, 2012). Here, the CH3 groups of I, L & V residues and the backbone amides are isotope labeled. The methyl groups are sufficiently close (~8 Å) to 1H’s of the ligand to give rise to NOEs (blue dotted lines). The intermolecular NOEs can be used to calculate the structure of the complex and even differentiate between ambiguous crystallographic information as described in the publication.

Struct-elucidation

Obtaining high resolution structural information by NMR is a stand-alone process and it is therefore not necessary to have low resolution information (e.g. Binding Site Location) obtained before.


< Binding Orientation