.png){kind=icon}
Return
Structure-based virtual screening for TRPM8 modulators
.png){kind=icon}
OA
AI
DOI：10.3389/fddsv.2026.1770904.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Transient receptor potential melastatin 8 (TRPM8) is an emerging therapeutic target, yet the performance of available structural models for docking and optimal docking protocols for virtual screening (VS) remains unclear. Here, we benchmarked two available TRPM8 structural conformations (agonist-bound TRPM87WRE and antagonist-bound TRPM89B6G) using docking tools, Smina and rDock, using known TRPM8 inhibitors and property-matched decoys. rDock achieved the highest hit rates and outperformed Smina in ranking true actives at first-ranks than their corresponding decoys, whereas Smina showed a target-structure dependence on docking performance but delivered superior overall ranking quality across both target structures. Both docking tools displayed considerable overlap between active and decoy score distributions, indicating only moderate discriminatory power of docking scores alone. When prioritizing a small subset of top-ranked compounds, integrated screening approaches, particularly the consensus protocol, improved the recovery of true actives, while the hierarchical protocol achieved comparable performance at a substantially lower computational cost. Collectively, this work establishes a reproducible VS benchmark for TRPM8 and supports the use of different screening protocols to improve early hit identification.
Keywords:
benchmarking
ion channels
molecular docking
TRPM8
virtual screening
Journal
F
IF:
0
Papers:
25
Citations:
0
Organization
Cited Papers
ShareSaveShareSaveA practical guide to machine-learning scoring for structure-based virtual screening.png)
NATURE PROTOCOLS
NATURE PROTOCOLSIF16
PREAI
ShareSaveShareSaverDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acidsplos biology
OAAI
plos biologyIF3.6
OAAIShareSaveActivation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP
2ScienceOAAI
ScienceIF0
OAAIShareSave
View more