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Updated: May 30, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Targeting FKBP isoforms with small-molecule ligands
Elizabeth A Blackburn1, Malcolm D Walkinshaw
1The Centre for Translational and Chemical Biology, ISMB, University of Edinburgh, Edinburgh EH9 3JR, UK.
Abstract:
The FK506 binding protein (FKBP) family of proteins provide an interesting series of drug targets since different isoforms modulate diverse cellular pathways. There are therapeutic opportunities in the fields of cancer therapy, neurodegenerative conditions and psychiatric disorders. X-ray crystallographic or NMR data are available for eight of fourteen human FKBPs covering ten of the twenty-two different FKBP domains. We have made a detailed sequence and structural comparison of human FKBP domains. These data show that the chemical scaffolds common to the immunosuppressive inhibitors FK506 and rapamycin bind to the most conserved region of the binding site. This observation opens the way to the design of isoform specific inhibitors.
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