Molecular Interactions of Renin with Chikusetsusaponin IV and Momordin IIc

Hai-Ling Zhang,Gui-Lan Zhu,Xiao-Tian Chen

doi:10.1155/2019/6720616

Abstract

The paper dealt with the molecular mechanism for the binding sites and driving forces of renin with chikusetsusaponin IV and momordin IIc by means of molecular docking and free energy calculation based on the crystal structure. The result showed that renin and the saponins fit well. As shown by LigPlot + software analyzing the hydrogen bonding and hydrophobic effect between renin and the saponins, the amino acid residues such as Ser230, Tyr85, and Tyr201 form the hydrogen bonds, with S3sp, S3, and S2′ being the active pockets. In addition, there are relatively strong hydrophobic interactions of renin with saponins in S3sp, S3, S2, S1, S1′, and S2′, with Gly228, Val36, Ala229, Gln19, Met303, Gln135, Ser41, Ile137, Asp38, Arg82, and Tyr83 being the key amino acids. The dynamics reached equilibration after about 1000 ps simulation with average root-mean-square deviations of 0.222 nm and 0.217 nm. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) yielded −1.10812 kcal/mol and −39.0587 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, a further confirmation that momordin IIc has stronger hydrogen bonding and hydrophobic effect in the inhibition of renin than the chikusetsusaponin IV.

Highlights

Complications such as hypertension, cardiovascular disease, and coronary heart disease are mostly caused by excessive activation of the renin-angiotensin system (RAS), which is mainly composed of angiotensinogen (AGT), renin, angiotensin-converting enzyme (ACE), angiotensin I (Ang I), angiotensin II (Ang II), and its receptors such as AT1 (AT1R) and AT2 (AT2R) [1, 2]
With molecular docking and dynamic simulation being the proven methods for the design of drugs, especially based on the three-dimensional structure of receptors, the interaction between the receptor and the ligand [23] and between the small macromolecular protein receptor and the molecular ligand can be assessed through the study of the key residues of amino acids, interaction sites, and free binding energy in the docking [24]. e paper investigated the interactions of chikusetsusaponin IV and momordin IIc with renin through molecular docking and dynamic simulation
The complexes existed in the active areas with low root mean square fluctuations (RMSF) such as r39Trp45, Met107- r112, Leu2224-Ser235, and Ala314- r318 where the renin and the saponins interacted. e RMSFs of the residues of amino acids were calculated, as shown in Figure 3, in order to describe the fluctuations of the complexes

Summary

Introduction

Complications such as hypertension, cardiovascular disease, and coronary heart disease are mostly caused by excessive activation of the renin-angiotensin system (RAS), which is mainly composed of angiotensinogen (AGT), renin, angiotensin-converting enzyme (ACE), angiotensin I (Ang I), angiotensin II (Ang II), and its receptors such as AT1 (AT1R) and AT2 (AT2R) [1, 2]. Modern pharmacological studies have found that ginseng saponins have a variety of biological activities that have certain pharmacological effects on the cardiovascular system, kidney, myocardium, diabetes, and tumors [10, 11]. With molecular docking and dynamic simulation being the proven methods for the design of drugs, especially based on the three-dimensional structure of receptors, the interaction between the receptor and the ligand [23] and between the small macromolecular protein receptor and the molecular ligand can be assessed through the study of the key residues of amino acids, interaction sites, and free binding energy in the docking [24]. With molecular docking and dynamic simulation being the proven methods for the design of drugs, especially based on the three-dimensional structure of receptors, the interaction between the receptor and the ligand [23] and between the small macromolecular protein receptor and the molecular ligand can be assessed through the study of the key residues of amino acids, interaction sites, and free binding energy in the docking [24]. e paper investigated the interactions of chikusetsusaponin IV and momordin IIc with renin through molecular docking and dynamic simulation

Materials and Methods

Results and Analysis

Chikusetsusaponin IV Momordin IIc

Conclusions