以蒙地卡羅法研究ssDNA模型分子在自由溶液中之電泳行為

Abstract

本研究分為兩大部分，在第一部分中，我們利用蒙地卡羅法及尺度分析，研究當末端有兩個反應基時，可逆環狀結構開啟與密合的轉換機制中加上堆疊能量的影響。每個分子鏈末端具有兩個反應基，其作用位能為 ，而分子鏈中我們加上堆疊能量 的考量，使得分子鏈較偏好呈現直線狀態。我們的研究發現，分子由開啟狀態轉換到密合狀態時，除了需克服亂度上的損失，還要克服堆疊能量上的障礙；由密合狀態轉變為開啟狀態時，其能量障礙則是僅由binding energy所造成的。 另外關於第二部分，長度不同的DNA分子在自由溶液中電泳無法分離良好，因此常常使用凝膠或高分子溶液作為篩分的介質，使得DNA可以因大小的不同而分離，但凝膠電泳有其外加電場不能太大導致分析實驗冗長等缺點，所以另一個可選擇的方法乃是破壞原先的摩擦力與電力的平衡，將DNA分子尾端接上不帶電的分子團，此方法即End-Labeled Free-Solution Electrophoresis(ELFSE)。在本模擬中我們利用蒙地卡羅法及尺度分析，檢視ELFSE的分離效果，結果發現長度不同的DNA分子分離相當良好。且當不帶電的分子團切成兩段分別接上帶電分子鏈兩端時，分離速度又更加快速。而各種不同形式的不帶電分子團包括直鏈型、星狀型和環狀型的設計，則於速度區分上貢獻不大。最後，我們探討不帶電分子鏈的長短所造成的影響，結果發現較長的不帶鏈分子鏈適用於分離大範圍下各種不同長度的帶電分子鏈，但整體速度較慢為其缺點，反之，較短的不帶鏈分子鏈雖不適用於區分大範圍下各種不同長度的帶電分子鏈，但整體分離速度快速，可以縮短分析時間為其優點。

It is well-known that uniformly charged polyelectrolytes such as DNA migrate with the same mobility regardless of chain length. However, they may be separated by free solution electrophoresis if an uncharged particle is attached to the one end of the polyelectrolyte. On the basis of Monte Carlo simulations, the mobility μ of a polyelectrolyte of length Nc attached with an neutral polymer of length Nu is investigated. According to the Rouse (free-draining) picture, it is anticipated that the mobility becomes size-dependent and follows μ(Nc) ∝ Nc/(Nc+Nu). The additional resistance provided by the neutral section breaks the balance between the electric driving force (Nc) and hydrodynamic drag (Nc+ Nu). Our simulation results indicate that although the end label offers the broken symmetry but the aforementioned relation is not valid due to the interaction friction. With both ends are labeled with neutral polymers of Nu* and Nu-Nu*, it is found that the mobility increases as Nu*/(Nu-Nu*)→1. In weak electric field, the conformation may change from random coil to charge-neutral segregation regime as the ratio Nc/(Nc+ Nu) is decreased. Because the conformations are different with/without electric field, the Nernst-Einstein equation is not valid for end-labeled polyelectrolytes.