Depression treatment
Can docking find new NMDA blockers for Alzheimer’s?
Open access · cc by · source: Europe PMC
A pharmacophore-docking-MD pipeline screened ZINC against GluN2B NMDA receptors and nominated six compounds with better predicted solvation binding than ifenprodil—still untested in cells or people.
How this study connects
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Study at a glance
- Design
- Computational / modelling — Pharmacophore validation (20 known NMDA inhibitors + 380 DUDE decoys), ZINC virtual screen, Glide docking, MD/solvation free energy vs ifenprodil
- N
- N=6 · Six ZINC leads after 38,105 pharmacophore hits; pharmacophore test set 20 actives + 380 inactives
- Population
- In silico GluN2B/NMDAR ligands from ZINC and PDB ifenprodil-bound complexes; no new wet-lab or patient dosing
- Outcome
- Predicted binding (GlideScore, solvation free energy, ADMET) of six candidate Gly/NMDA antagonists versus ifenprodil
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Inspect source passages
Can docking find new NMDA blockers for Alzheimer’s?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Pharmacophore screening of ZINC left 38,105 hits.
only 38,105 hits were screened out
The test kit mixed 20 recognized NMDA inhibitors with 380 DUDE inactives.
a test kit database was created consisting of these 20 recognized NMDA inhibitors added to 380 molecules derived from the DUDE database
Key findings
Six ZINC molecules (including ZINC13729211 and ZINC07430424) showed high predicted affinity, hydrogen bonding, stability, and better solvation-based affinity than ifenprodil with acceptable ADMET; authors propose them as Gly/NMDA antagonist starting points.
Methodology
Built a pharmacophore from known NMDAR inhibitors, validated it on 20 actives plus 380 DUDE decoys, filtered ZINC (38,105 hits), docked to ifenprodil-bound NMDAR with Glide, then ranked ADMET and solvation free energies.
Limitations
No enzyme, cell, animal, or Alzheimer-patient data; docking and MM-PBSA cannot prove clinical NMDA blockade or safety.
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