Jeon Jae-Hyung, Sung Wokyung
Department of Physics and PCTP, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea,
J Biol Phys. 2014 Jan;40(1):1-14. doi: 10.1007/s10867-013-9333-9. Epub 2013 Dec 5.
Watson and Crick's epochal presentation of the double helix structure in 1953 has paved the way to intense exploration of DNA's vital functions in cells. Also, recent advances of single molecule techniques have made it possible to probe structures and mechanics of constrained DNA at length scales ranging from nanometers to microns. There have been a number of atomistic scale quantum chemical calculations or molecular level simulations, but they are too computationally demanding or analytically unfeasible to describe the DNA conformation and mechanics at mesoscopic levels. At micron scales, on the other hand, the wormlike chain model has been very instrumental in describing analytically the DNA mechanics but lacks certain molecular details that are essential in describing the hybridization, nano-scale confinement, and local denaturation. To fill this fundamental gap, we present a workable and predictive mesoscopic model of double-stranded DNA where the nucleotides beads constitute the basic degrees of freedom. With the inter-strand stacking given by an interaction between diagonally opposed monomers, the model explains with analytical simplicity the helix formation and produces a generalized wormlike chain model with the concomitant large bending modulus given in terms of the helical structure and stiffness. It also explains how the helical conformation undergoes overstretch transition to the ladder-like conformation at a force plateau, in agreement with the experiment.
1953年,沃森和克里克对双螺旋结构具有划时代意义的展示,为深入探索DNA在细胞中的重要功能铺平了道路。此外,单分子技术的最新进展使得在从纳米到微米的长度尺度上探测受限DNA的结构和力学成为可能。已经有许多原子尺度的量子化学计算或分子水平的模拟,但它们在计算上要求过高,或者在分析上不可行,无法描述介观水平上的DNA构象和力学。另一方面,在微米尺度上,蠕虫链模型在解析描述DNA力学方面非常有用,但缺乏描述杂交、纳米尺度限制和局部变性所必需的某些分子细节。为了填补这一基本空白,我们提出了一种可行且具有预测性的双链DNA介观模型,其中核苷酸珠子构成基本自由度。通过对角相对单体之间的相互作用给出链间堆积,该模型以解析的简单性解释了螺旋的形成,并产生了一个广义的蠕虫链模型,其伴随的大弯曲模量由螺旋结构和刚度给出。它还解释了螺旋构象如何在力平台上经历过度拉伸转变为梯状构象,这与实验结果一致。