Centre for Condensed Matter Theory, Indian Institute of Science, Bangalore 560012, India.
J Chem Phys. 2012 Feb 14;136(6):065106. doi: 10.1063/1.3682780.
In an effort to design efficient platform for siRNA delivery, we combine all atom classical and quantum simulations to study the binding of small interfering RNA (siRNA) by pristine single wall carbon nanotube (SWCNT). Our results show that siRNA strongly binds to SWCNT surface via unzipping its base-pairs and the propensity of unzipping increases with the increase in the diameter of the SWCNTs. The unzipping and subsequent wrapping events are initiated and driven by van der Waals interactions between the aromatic rings of siRNA nucleobases and the SWCNT surface. However, molecular dynamics (MD) simulations of double strand DNA (dsDNA) of the same sequence show that the dsDNA undergoes much less unzipping and wrapping on the SWCNT in the simulation time scale of 70 ns. This interesting difference is due to smaller interaction energy of thymidine of dsDNA with the SWCNT compared to that of uridine of siRNA, as calculated by dispersion corrected density functional theory (DFT) methods. After the optimal binding of siRNA to SWCNT, the complex is very stable which serves as one of the major mechanisms of siRNA delivery for biomedical applications. Since siRNA has to undergo unwinding process with the effect of RNA-induced silencing complex, our proposed delivery mechanism by SWCNT possesses potential advantages in achieving RNA interference.
为了设计高效的 siRNA 递释平台，我们结合全原子经典和量子模拟来研究小干扰 RNA（siRNA）与原始单壁碳纳米管（SWCNT）的结合。我们的结果表明，siRNA 通过解开其碱基对强烈结合到 SWCNT 表面，并且解开的倾向随着 SWCNT 直径的增加而增加。解开和随后的缠绕事件是由 siRNA 核碱基的芳环与 SWCNT 表面之间的范德华相互作用引发和驱动的。然而，相同序列的双链 DNA（dsDNA）的分子动力学（MD）模拟表明，在 70ns 的模拟时间尺度内，dsDNA 在 SWCNT 上经历的解开和缠绕要少得多。这种有趣的差异是由于与 siRNA 的尿嘧啶相比，dsDNA 的胸腺嘧啶与 SWCNT 的相互作用能更小，这是通过色散校正密度泛函理论（DFT）方法计算得出的。siRNA 与 SWCNT 最佳结合后，复合物非常稳定，这是 siRNA 用于生物医学应用的递释的主要机制之一。由于 siRNA 必须在 RNA 诱导沉默复合物的作用下经历解链过程，我们提出的 SWCNT 递释机制在实现 RNA 干扰方面具有潜在优势。
