ArticleChemMedChem2026
Not Quite Folded: Challenges in Predicting the hNPS-hNPSR-Ile107 Complex With AlphaFold2 Multimer.
Article in ChemMedChem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
1 citing paper in PubMed.
- Not Quite Folded: Challenges in Predicting the hNPS-hNPSR-Ile107 Complex With AlphaFold2 Multimer.ChemMedChem · 2026Article
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Authors and funding
12 authors.
Funding
Abstract
The human neuropeptide S (NPS) receptor (NPSR) is a Class A peptide G protein-coupled receptor expressed in the central nervous system and endogenously activated by NPS, a 20-mer peptide. NPSR activation promotes cellular excitability via Gq and Gs signalling. Studies suggest that receptor antagonists may reduce drug-seeking behaviours, whilst agonists represent innovative non-sedating anxiolytics with memory-enhancing effects. Despite its therapeutic potential, NPSR remains poorly characterised, with neither experimental receptor structures nor drug-like clinical candidates available. To fill this gap, we applied a previously validated AlphaFold2 Multimer-based protocol to model the hNPS-hNPSR complex. The model showing higher stability in molecular dynamics simulations and consistency with known structure-activity relationships served as template to design novel hNPS analogues. However, experimental validation through synthesis and in vitro pharmacological evaluation of 20 novel truncated cyclic peptides revealed the model's inability to capture hNPS bioactive conformation, as most analogues were inactive as agonists. By exploiting the stereochemical switch in hNPS hinge region, we identified four novel cyclic antagonists (17-20, pA
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.