Citation: Wen-Li YAN, Zhen LIANG, Xing-Lian YU, Rong ZHANG. Mechanism Study of Aliskiren and Its Analogues by Molecular Dynamic Simulation[J]. Chinese Journal of Structural Chemistry, ;2022, 41(3): 220317. doi: 10.14102/j.cnki.0254-5861.2011-3308 shu

Mechanism Study of Aliskiren and Its Analogues by Molecular Dynamic Simulation

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

Corresponding author: Rong ZHANG, zhangr@gdpu.edu.cn
Received Date: 11 July 2021
Accepted Date: 29 October 2021

Fund Project: Talents Introduction Foundation for Universities of Guangdong Province GD 2011the Science and Technology Planning Project of Guangzhou 2013J4100071

Figures(10)

The further interaction mechanism towards renin inhibitors was revealed by comparison of renin with different active inhibitors in aqueous solution. Molecular docking and molecular dynamics (MD) simulations were combined for the research. The results reflected that electrostatic and hydrophobic effects were the major interactions for renin inhibitors forming complexes with renin, and some residues were the key to the formation of complex, especially Asp38/Asp226. The factor of different activities performed in renin inhibitors was illustrated as well. For the higher active renin inhibitor, it possessed stronger affinity with renin, and its detected conformation was more extended to fit for the key binding site. This promoted the capacity to form special interactions with the key residues. While conformation of the lower active renin inhibitor performed folded in the active site of renin, the interactions to the important pocket S3sp was restricted, resulting in undesirable bioactivity.
- renin inhibitors,
- mechanism,
- molecular docking,
- molecular dynamics (MD) simulations
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