Monte Carlo simulations of locally melted supercoiled DNAs in 20 mM ionic strength.
Monte Carlo simulations of locally melted supercoiled DNAs in 20 mM ionic strength.
复制标题
DOI：
10.1016/s0006-3495(04)74357-x
复制
发表时间：
2004-05
影响因子：
3.4
通讯作者：
Christopher A. Sucato;D. Rangel;Dan Aspleaf;B. Fujimoto;J. Michael Schurr
中科院分区：
文献类型：
--
作者：
Christopher A. Sucato;D. Rangel;Dan Aspleaf;B. Fujimoto;J. Michael Schurr
在20mM离子强度下，对未熔化和局部熔化的超螺旋dna的介观模型进行了模拟，其连接差范围为Δ =0至−26转，或超螺旋密度σ=0至−0.062。一个包含m= 0,28或56熔化基对的域（总共4349个）简单地通过一个适当长度的区域来建模，该区域的扭转和弯曲弹性常数大大降低。根据保存的构型计算平均结构性能，并采用可逆功协议计算超卷自由能ΔGsc。发现双相区和熔化区（此处定义）之间的交叉扭曲很小，可以忽略不计。发现对角化惯性张量的总扭度、旋转半径和有序元是与双工区相关的剩余连接差（< Δ r >）的近似泛函数，与m无关。然而，三级结构的可变形性，表现为这些相同性质的变化，并不是< Δ r >的普遍函数，而是取决于。由于离子强度较低，ΔGsc随< Δ r >的变化比< Δ r > 2的变化更强烈。由模拟的ΔGsc得到的扭转能参数ET < Δ r >和熔化区的净扭转应变< TD >与m无关，因此也与熔化区的扭转弹性常数和弯曲弹性常数无关。然而，ET随着−< Δ r >线性增加，这导致1)，对于任何给定的< Δ r >，当ET由观测值和< Δ r >由Bauer和Benham协议确定时，ET都有一个小的高估；2)相对于实际斜率（固定< Δ r >），通过Bauer和Benham协议获得的表观斜率（Δ−Δ dET/dT）显著增强。在考虑这两种效应后，理论和实验ET值与−dET/dT值相当吻合。对于较大的熔化区域优先发现在相互缠绕臂之间的连接域，而不是在相互缠绕臂末端的顶端区域。
Mesoscopic models of unmelted and locally melted supercoiled DNAs in 20mM ionic strength are simulated over a range of linking difference from Δℓ=0 to −26 turns, or superhelix density fromσ=0 to −0.062. A domain containingm=0, 28, or 56 melted basepairs (out of 4349 total) is modeled simply by a region of suitable length with substantially reduced torsion and bending elastic constants. Average structural properties are calculated from the saved configurations, and a reversible work protocol is used to calculate the supercoiling free energy, ΔGsc. The cross-writhe between duplex and melted regions (defined herein) is found to be negligibly small. The total writhe, radius of gyration, and ordered elements of the diagonalized inertial tensor are found to be nearly universal functions of the residual linking difference (〈Δℓr〉) associated with the duplex region, independent ofm. However, deformability of the tertiary structure, as manifested by the variance of those same properties, is not a universal function of 〈Δℓr〉, but depends uponm. ΔGsc varies with 〈Δℓr〉 more strongly than 〈Δℓr〉2 due to the low ionic strength. The twist energy parameter, ET, obtained from the simulated ΔGsc,〈Δℓr〉, and net twisting strain of the melted region,〈TD〉, is found to be independent ofm, hence also of the torsion and bending elastic constants of the melted region. However, ET increases linearly with −〈Δℓr〉, which leads to 1), a small overestimation of ET for any given 〈Δℓr〉, when ET is determined from the observedand 〈Δℓr〉 by the protocol of Bauer and Benham; and 2), a significant enhancement of the apparent slope, −dET/dT, obtained via the protocol of Bauer and Benham, relative to the actual slopeatfixed 〈Δℓr〉. After taking these two effects into account, the theoretical and experimental ET values and −dET/dT values agree rather well. For the largerthe melted regions are found preferentially in the linker domains between interwound arms, rather than in the apical regions at the ends of interwound arms.