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Updated: Aug 14, 2026

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
Published on: June 23, 2026
Human P2Y(6) receptor: molecular modeling leads to the rational design of a novel agonist based on a unique
Stefano Costanzi1, Bhalchandra V Joshi, Savitri Maddileti
1NIDDK, National Institutes of Health, DHHS, Bethesda, Maryland 20892. USA. stefanoc@mail.nih.gov
Abstract:
Combining molecular dynamics (MD) in a hydrated phospholipid (DOPC) bilayer, a Monte Carlo search, and synthesis of locked nucleotide analogues, we discovered that the Southern conformation of the ribose is preferred for ligand recognition by the P2Y(6) receptor. 2'-Deoxy-(S)-methanocarbaUDP was found to be a full agonist of the receptor and displayed a 10-fold higher potency than that for the corresponding flexible 2'-deoxyUDP. MD results also suggested a conformational change of the second extracellular loop consequent to agonist binding.
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