Abstract: Recent studies have identified Sarmentol H (SMH), a natural product isolated from Sedum sarmentosum Bunge, as a novel FXR agonist with a unique scaffold structure and promising in vitro and in vivo activities. However, the precise interaction mechanism between SMH and FXR remains unclear. In this study, we employed an integrated computational approach combining molecular docking, molecular dynamics simulations, and binding free energy calculations to elucidate the binding mode between SMH and FXR in detail. By comparing structural dynamics and binding free energetics, we identified the optimal binding mode of SMH with FXR and pinpointed key amino acid residues critical for SMH recognition and binding.

Key words: FXR; Sarmentol H, Interaction Mechanism