Numerical analysis of interaction of carbon nano particles with lipid bilayer containing ergosterol using molecular dynamics
Date: Wednesday April 15, 2009
Location: PERC Seminar Room PS&T 205
Time: 4:00 pm-
Speaker: Hideya Nakamura
Polyhydroxy fullerenes (PHFs) have been recently expected as a novel and effective antifungal material. So far, some experimental results have showed PHFs can inactivate fungis which cannot be inactivated by conventional antifungal compounds. However, despite great advantages of PHFs as an antifungal material, the mechanism of antifungal PHF’s action has not been cleared yet. Some experimental results also show the ability of antifungal PHFs depends on the degree of hydroxylation, i.e., number of hydroxyl groups on PHFs. Therefore, optimization of the degree of hydroxylation is strongly required to develop more effective antifungal PHFs.
So far, a number of antifungal compounds (e.g., amphotericin B in Fig. 1) have been used. Although the mechanism of action of conventional antifungal compounds has not been fully elucidated, it is commonly accepted that these compounds preferentially interact with ergosterol which is one of the major components of the fungal cell membrane, resulting in forming transmembrane pores and/or decreasing fluidity of the membrane, and these lead to fungal cell death [1]. As shown in Fig.1, most of the conventional antifungal compounds consist of two parts: a rigid apolar part composed of conjugated C-C double bonds and a polar part comprising a number of hydroxyl groups. This structure (conjugated C-C double bonds and multiple OH groups) is similar to PHF’s structure. Therefore, we propose a hypothesis about the mechanism of antifungal PHF’s action: mechanism of the PHF’s action may be similar to that of conventional antifungal compounds, i.e., antifungal PHFs may interact with ergosterol in fungal cell membrane, resulting in fungal cell death.
In recent years, computer simulations have become a powerful approach for detailed analysis of nano-bio systems. Molecular dynamics (MD) is one of the useful numerical schemes to understand nano-bio systems from atomistic level and have been applied to many lipid membrane studies [e.g. 2-6]. However, the interaction of PHFs with lipid bilayer containing ergosterol has not been numerically analyzed yet.
In this study, interaction of PHFs with lipid bilayer containing ergosterol has been numerical analyzed using MD. The final goals of this study are (i) elucidation of the inactivation mechanism of fungi by PHFs, (ii) specifying features and advantages of antifungal PHFs as compared to pristine C60 and a conventional antifungal compound, and (iii) determination of optimal structure (i.e., degree of hydroxylation) of antifungal PHFs through MD simulations. So far, the first numerical models in which C60 or a PHF (C60(OH)24), water, lipid and ergosterol molecules are taken into account have been developed (Fig. 2).
In this group meeting, I would like to talk about following subjects:
1. Simulation details
2. Calculation results obtained so far
3. Next plans (for reasonable comparing and correlating with experimental results, what kinds of physical values we should calculate?)
I am looking forward to your valuable comments/suggestions.
References:
[1] Kavanagh, Fungi Biology and Applications, p. 1265. Wiley, New York (2005)
[2] Sternal et al. J Mol Model, 10 (2004) 223-232.
[3] Czub and Baginski. J Phys Chem B, 110 (2006) 16743-16753.
[4] Qiao et al. Nano Lett, 7 (2007) 614-619.
[5] Bedrov et al. J Phys Chem B, 112 (2008) 2078-2084.
[6] Wong-Ekkabut et al. Nature Nanotechnol., 3 (2008) 363-368.
