title: Renin inhibition by soyasaponin I: a potent native anti-hypertensive compound.
abstract: One way to control hypertension is inactivation of the Renin- Angiotensin- Aldosterone System (RAAS). Inhibition of renin as a rate-limiting step of this system is an effective way to stop up RAAS. It has been proved that soyasaponin I, an herbal compound obtained from soybeans, has anti-hypertensive effect via renin inhibition, so it has the potential of being an anti-hypertensive drug. Herein, some theoretical approaches such as Docking Simulation, Molecular Dynamics (MD) Simulation and MMPBSA analysis have been used to study how soyasaponin I inhibits renin at the structural level. The results of docking simulation and hydrogen bond pattern show that this ligand is able to bind to the active site of renin and a region near the active site. Results of MD simulation for renin - soyasaponin I complexes confirm that soyasaponin I binds to the active site of renin and has inhibition effect on it via competing with the substrate. Besides, according to MMPBSA analysis, the binding free energy for renin - soyasaponin I complex is -42.61 kcal/mol when it binds to the active site. Comparing to the peptide obtained from angiotensinogen, ΔG = -74.96 kcal/mol, it may inferred that although binding of soyasaponin I to the active site of renin does not have a complete competition with the substrate, it might attenuate the formation of renin - angiotensinogen complex and have partial non-competitive effect. The results of this survey might be helpful to design partial non - competitive renin inhibitors with pharmaceutical capability.
authors.affiliation: a Department of Biophysics , Tarbiat Modares University , Tehran , Iran.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Tavassoli
authors.affiliation: a Department of Biophysics , Tarbiat Modares University , Tehran , Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Taghdir
authors.affiliation: a Department of Biophysics , Tarbiat Modares University , Tehran , Iran.
authors.forename: Bijan
authors.initials: B
authors.lastname: Ranjbar
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020134:Catalytic Domain; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000517:prevention & control*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D012083:Renin / Q000737:chemistry / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012503:Saponins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013816:Thermodynamics; D000092502:Renin Inhibitors
chemical_list: D000959:Antihypertensive Agents; D009828:Oleanolic Acid; D012083:Renin; D012503:Saponins; D000092502:Renin Inhibitors; C056684:soyasaponin I
keywords: docking; hypertention; molecular dynamics; renin inhibitor; soyasaponin I