Matsumoto Atsushi, Olson Wilma K
Department of Chemistry & Chemical Biology, Rutgers, The State University of New Jersey, Wright-Rieman Laboratories, 610 Taylor Road, Piscataway, NJ 08854-8087, and Quantum Bioinformatics Team, Japan Atomic Energy Agency, 8-1 Umemidai, Kizu, Kyoto 619-0215, Japan.
Multiscale Model Simul. 2006;5(4):1227-1247. doi: 10.1137/060663040.
A newly developed, coarse-grained treatment of the low-frequency normal modes of DNA has been adapted to study the torsional properties of fully extended, double-helical molecules. Each base pair is approximated in this scheme as a rigid body, and molecular structure is described in terms of the relative position and orientation of successive base pairs. The torsional modulus C is computed from the lowest-frequency normal twisting mode using expressions valid for a homogeneous, naturally straight elastic rod. Fluctuations of local dimeric structure, including the coupled variation of conformational parameters, are based on the observed arrangements of neighboring base pairs in high-resolution structures. Chain ends are restrained by an elastic energy term. The calculations show how the end-to-end constraints placed on a naturally straight DNA molecule, in combination with the natural conformational features of the double helix, can account for the substantially larger torsional moduli determined with state-of-the-art, single-molecule experiments compared to values extracted from solution measurements and/or incorporated into theories to account for the force-extension properties of single molecules. The computed normal-mode frequencies and torsional moduli increase substantially if base pairs are inclined with respect to the double-helical axis and the deformations of selected conformational variables follow known interdependent patterns. The changes are greatest if the fluctuations in dimeric twisting are coupled with parameters that directly alter the end-to-end displacement. Imposed restraints that mimic the end-to-end conditions of single-molecule experiments then impede the twisting of base pairs and increase the torsional modulus. The natural inclination of base pairs concomitantly softens the Young's modulus, i.e., ease of duplex stretching. The analysis of naturally curved DNA points to a drop in the torsional modulus upon imposed extension of the double-helical molecule.
一种新开发的、用于处理DNA低频正常模式的粗粒度方法已被应用于研究完全伸展的双螺旋分子的扭转特性。在该方案中，每个碱基对被近似为一个刚体，分子结构通过连续碱基对的相对位置和取向来描述。扭转模量C是根据最低频率的正常扭转模式，使用对均匀、自然伸直的弹性杆有效的表达式计算得出的。局部二聚体结构的波动，包括构象参数的耦合变化，基于高分辨率结构中相邻碱基对的观察排列。链端由一个弹性能项约束。计算结果表明，对自然伸直的DNA分子施加的端到端约束，与双螺旋的自然构象特征相结合，如何能够解释与从溶液测量中提取的值和/或纳入理论以解释单分子的力-伸长特性相比，在最先进的单分子实验中确定的显著更大的扭转模量。如果碱基对相对于双螺旋轴倾斜，并且选定构象变量的变形遵循已知的相互依赖模式，则计算出的正常模式频率和扭转模量会大幅增加。如果二聚体扭转的波动与直接改变端到端位移的参数耦合，则变化最大。模拟单分子实验端到端条件的施加约束随后会阻碍碱基对的扭转并增加扭转模量。碱基对的自然倾斜同时会软化杨氏模量，即双链拉伸的难易程度。对自然弯曲的DNA的分析表明，在双螺旋分子施加延伸时，扭转模量会下降。
