Extracellular domain of TREM2 possess two distinct ligand recognition sites: Insights from machine-learning guided docking and all-atoms molecular dynamics simulations.

ABSTRACT: The myeloid-specific triggering receptors expressed on myeloid cells 2 (TREM2) is a group of class I receptors expressed in brain microglia plays a decisive role in neurodegenerative diseases such as Alzheimer's disease (AD) and Nasu Hakola disease (NHD). The extracellular domain (ECD) of TREM2 interacts with a wide-range of ligands, yet the molecular mechanism underlying recognition of such ligands to this class I receptor remains underexplored. Herein, we undertook a systematic investigation for exploring the mode of ligand recognition in immunoglobulin-like ectodomain by employing both knowledge-based and machine-learning guided molecular docking approach followed by the state-of-the-art all atoms molecular dynamics (MD) simulations. Besides the known binding site formed by complementar

SUBMITTER: Mishra S 

PROVIDER: S-EPMC11759634 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature