Structure-based virtual screening for TRPM8 modulators
File(s)
Published version
Author(s)
James, Nivya
Ballester, Pedro
Type
Journal Article
Abstract
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.
Date Issued
2026-01-28
Date Acceptance
2026-01-13
Citation
Frontiers in Drug Discovery, 2026, 6
ISSN
2674-0338
Publisher
Frontiers Media S.A.
Journal / Book Title
Frontiers in Drug Discovery
Volume
6
Copyright Statement
© 2026 James and Ballester. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Publication Status
Published
Article Number
1770904
Date Publish Online
2026-01-28