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초록

Molecular dynamics (MD) simulations generate high-dimensional trajectory data that require systematic analysis to extract scientifically interpretable structural and dynamical features. In this study, the glucagon-like peptide-1 receptor (GLP-1R) was employed as a model system to investigate its interactions with the endogenous ligand GLP-1(736) and two clinically relevant therapeutic analogs, semaglutide and tirzepatide. For each ligand-receptor complex, three independent 1 0 0 - ns MD simulations were performed using GROMACS. Trajectory data were processed to extract root mean square deviation (RMSD) profiles and to quantify salt bridge occupancies across key structural domains, including transmembrane (TM) helices, extracellular loops (ECLs), and N-terminal domain (NTD). Comparative analysis across ECL regions revealed region-specific variations in the correlation between salt bridge persistence and backbone stability. While certain regions demonstrated partial concordance between these metrics, other regions, particularly NTD, exhibited complete decoupling. These findings indicate that salt bridge occupancy alone is insufficient as a predictor of structural stability and should be integrated with additional parameters in comprehensive trajectory analyses. This case study provides evidence that trajectory data analysis can yield scientifically interpretable insights into receptor dynamics, establishing a foundation for systematic, data-driven approaches in G proteincoupled receptor (GPCR) research.

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