TRPM8 protein dynamics correlates with ligand structure and cellular function.

ABSTRACT: Protein dynamics have emerged as a key feature associated with function in various systems. Here, NMR-based studies coupled with computational cheminformatics and cellular function are leveraged to identify a relationship between the human cold and menthol receptor TRPM8 dynamics, chemical structure, and cellular potency. TRPM8 is a validated target for a variety of pain indications but generally has been clinically limited by on-target side effects impacting thermosensing and thermoregulation. This study shows that cheminformatic analysis of a TRPM8 regulating small molecule ligand library correlates with cellular function. Electrophysiology studies further validate the relationship and show a correlation between chemical structure and functional features such as compound potency. Solutio

SUBMITTER: Mebrat MD 

PROVIDER: S-EPMC12132250 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature