Journal of Molecular Modeling

, Volume 16, Issue 1, pp 107–118 | Cite as

Hemolytic mechanism of dioscin proposed by molecular dynamics simulations

  • Fu Lin
  • Renxiao WangEmail author
Original Paper


Saponins are a class of compounds containing a triterpenoid or steroid core with some attached carbohydrate modules. Many saponins cause hemolysis. However, the hemolytic mechanism of saponins at the molecular level is not yet fully understood. In an attempt to explore this issue, we have studied dioscin—a saponin with high hemolytic activity—through extensive molecular dynamics (MD) simulations. Firstly, all-atom MD simulations of 8 ns duration were conducted to study the stability of the dioscin–cholesterol complex and the cholesterol–cholesterol complex in water and in decane, respectively. MM-GB/SA computations indicate that the dioscin–cholesterol complex is energetically more favorable than the cholesterol–cholesterol complex in a non-polar environment. Next, several coarse-grained MD simulations of 400 ns duration were conducted to directly observe the distribution of multiple dioscin molecules on a DPPC-POPC-PSM-CHOL lipid bilayer. Our results indicate that dioscin can penetrate into the lipid bilayer, accumulate in the lipid raft micro-domain, and then bind cholesterol. This leads to the destabilization of lipid raft and consequent membrane curvature, which may eventually result in the hemolysis of red cells. This possible mechanism of hemolysis can well explain some experimental observations on hemolysis.


Top- and side-view of the last snapshot after coarse-grained molecular dynamics (CGMD) simulation of three dioscin molecules on the DPPC-POPC-PSM-CHOL membrane


Hemolysis Saponin Molecular dynamics Coarse-grained model 



The authors are grateful for the financial support of the Chinese National Natural Science Foundation (Grants No.20772149 & No. 90813006), the Chinese Ministry of Science and Technology (the 863 high-tech project, Grant No. 2006AA02Z337), and the Science and Technology Commission of Shanghai Municipality (Grant No. 074319113). The crystal structure of cholesterol isobutyl carbonate was provided by Prof. Ja P. Young at Sookmyung Women’s University. The MARTINI force field was provided by Prof. Siewert J. Marrink at University of Groningen. The authors are also grateful to Prof. Biao Yu and his student Yibing Wang at the Shanghai Institute of Organic Chemistry for their helpful discussions.

Supplementary material

894_2009_523_MOESM1_ESM.doc (5.2 mb)
ESM 1 Details of some computational tasks, Table S1-S6, and Figures S1-S7 described in this manuscript. This material is available upon request to the authors. (DOC 5327 kb)


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiPeople’s Republic of China

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