SHOP: receptor-based scaffold hopping by GRID-based similarity searches

Research output: Contribution to journalJournal articleResearchpeer-review

Rikke Bergmann, Tommy Liljefors, Morten D Sørensen, Ismael Zamora

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.
Original languageEnglish
JournalJournal of Chemical Information and Modeling
Volume49
Issue number3
Pages (from-to)658-669
ISSN1549-9596
DOIs
Publication statusPublished - 2009

ID: 11175353