SHOP: receptor-based scaffold hopping by GRID-based similarity searches
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SHOP: receptor-based scaffold hopping by GRID-based similarity searches. / Bergmann, Rikke; Liljefors, Tommy; Sørensen, Morten D; Zamora, Ismael.
I: Journal of Chemical Information and Modeling, Bind 49, Nr. 3, 2009, s. 658-669.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - SHOP: receptor-based scaffold hopping by GRID-based similarity searches
AU - Bergmann, Rikke
AU - Liljefors, Tommy
AU - Sørensen, Morten D
AU - Zamora, Ismael
PY - 2009
Y1 - 2009
N2 - A new field-derived 3D method for receptor-based scaffold hopping, implemented in the software SHOP, is presented. Information from a protein-ligand complex is utilized to substitute a fragment of the ligand with another fragment from a database of synthetically accessible scaffolds. A GRID-based interaction profile of the receptor and geometrical descriptions of a ligand scaffold are used to obtain new scaffolds with different structural features and are able to replace the original scaffold in the protein-ligand complex. An enrichment study was successfully performed verifying the ability of SHOP to find known active CDK2 scaffolds in a database. Additionally, SHOP was used for suggesting new inhibitors of p38 MAP kinase. Four p38 complexes were used to perform six scaffold searches. Several new scaffolds were suggested, and the resulting compounds were successfully docked into the query proteins.
AB - A new field-derived 3D method for receptor-based scaffold hopping, implemented in the software SHOP, is presented. Information from a protein-ligand complex is utilized to substitute a fragment of the ligand with another fragment from a database of synthetically accessible scaffolds. A GRID-based interaction profile of the receptor and geometrical descriptions of a ligand scaffold are used to obtain new scaffolds with different structural features and are able to replace the original scaffold in the protein-ligand complex. An enrichment study was successfully performed verifying the ability of SHOP to find known active CDK2 scaffolds in a database. Additionally, SHOP was used for suggesting new inhibitors of p38 MAP kinase. Four p38 complexes were used to perform six scaffold searches. Several new scaffolds were suggested, and the resulting compounds were successfully docked into the query proteins.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1021/ci800391v
DO - 10.1021/ci800391v
M3 - Journal article
C2 - 19265417
VL - 49
SP - 658
EP - 669
JO - Journal of Chemical Information and Modeling
JF - Journal of Chemical Information and Modeling
SN - 1549-9596
IS - 3
ER -
ID: 11175353