关键词: 肾素, 皂苷, 分子对接, 分子动力学模拟, 分子力学泊松-波尔兹曼表面积

Abstract: Two saponins from Kochia scoparia fruit, momordin Ic and 2′-O-β-D-glucopyranosyl momordin Ic, were found to strongly inhibit in vitro renin activity, and three different methods were used to investigate their inhibitory mechanisms. Molecular docking showed that both saponins were bound well to renin to form 9 and 4 hydrogen bonds, respectively. Amino acid residues Ser230 and Tyr231 were important for hydrogen bonds and residues Ala229, Met303, His301, Asp38, Arg82, Tyr83 and Ile137 functioned by hydrophobic interactions with both saponins. Molecular dynamics of the two complexes reached equilibration after about 1 000 ps simulation with average root-mean-square deviations of 0.224 and 0.219 nm, respectively. The two saponins also reduced the root-mean-square fluctuation of 160 amino acids in renin. The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method yielded .44.36 and .62.46 kcal/mol total binding energy for the two complexes respectively, which were primarily contributed by electrostatic and Van der Waals interaction energies, and the binding was strongly unfavored by polar solvation energy. These results elucidated the molecular mechanisms of interaction between renin and two saponin inhibitors.

Key words: renin, saponin, molecular docking, molecular dynamics simulation, molecular mechanics Poisson-Boltzmann surface area