Molecular mechanical studies of DNA flexibility: coupled backbone torsion angles and base-pair openings.
Molecular mechanical studies of DNA flexibility: coupled backbone torsion angles and base-pair openings.
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DOI：
10.1073/pnas.79.18.5537
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发表时间：
1982-09
影响因子：
11.1
通讯作者：
J. Keepers;P. Kollman;P. Weiner;T. James
中科院分区：
文献类型：
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作者：
J. Keepers;P. Kollman;P. Weiner;T. James
对[d(C-G-C-G-A-A-T-T-C-G-C-G-C-G)](2)和[d(A)](12).[d(T)](12)的“类B-DNA”结构进行了分子力学研究.每个主链扭转角(Psi、Phi、omega、omega‘、Phi’)都被“强迫”为正常B-DNA值(g(+)、t、g(-)、g(-)、t构象)的替代值。补偿扭转角的变化保留了双螺旋中大部分的碱基堆积能量。在这项研究的第二部分，一次一个嘌呤N3-嘧啶N1的距离被强制为6A的值，以试图模拟使DNA质子交换数据合理化所需的碱基打开运动。当6-A限制被去除时，许多结构恢复到正常的Watson-Crick氢键结构，但一些结构被捕获在能量比起始B-DNA结构高约5kcal/mol的结构中。这些结构的相对能量，其中一些涉及非Watson-Crick胸腺嘧啶C2(羰基)[unk]腺嘌呤6NH(2)氢键，与Mandal等人提出的“碱基对开放状态”的DeltaH定性一致。4-6千卡/摩尔[Mandal，C.，Kallenbach，N.R.&England，S.W.(1979)J.Mol.比奥尔。135,391-411]。从这项研究中出现的DNA柔韧性图描绘了脊椎在纳秒时间尺度上的局部扭转极小值之间经历快速运动。主链运动主要定位在二核苷片段内，通常不是沿链或跨碱基对的构象耦合。基座运动的幅度比主干运动小得多。基座滑动允许亚米诺N-H交换，但它是局部化的，任何时候都只有一小部分N-H基团暴露出来。堆积和氢键导致分子中心有一个坚硬的碱基核心，这说明了DNA的流体力学性质。
Molecular mechanics studies have been carried out on "B-DNA-like" structures of [d(C-G-C-G-A-A-T-T-C-G-C-G)](2) and [d(A)](12).[d(T)](12). Each of the backbone torsion angles (psi, phi, omega, omega', phi') has been "forced" to alternative values from the normal B-DNA values (g(+), t, g(-), g(-), t conformations). Compensating torsion angle changes preserve most of the base stacking energy in the double helix. In a second part of the study, one purine N3-pyrimidine N1 distance at a time has been forced to a value of 6 A in an attempt to simulate the base opening motions required to rationalize proton exchange data for DNA. When the 6-A constraint is removed, many of the structures revert to the normal Watson-Crick hydrogen-bonded structure, but a number are trapped in structures approximately 5 kcal/mol higher in energy than the starting B-DNA structure. The relative energy of these structures, some of which involve a non-Watson-Crick thymine C2(carbonyl)[unk]adenine 6NH(2) hydrogen bond, are qualitatively consistent with the DeltaH for a "base pair-open state" suggested by Mandal et al. of 4-6 kcal/mol [Mandal, C., Kallenbach, N. R. & Englander, S. W. (1979) J. Mol. Biol. 135, 391-411]. The picture of DNA flexibility emerging from this study depicts the backbone as undergoing rapid motion between local torsional minima on a nanosecond time scale. Backbone motion is mainly localized within a dinucleoside segment and generally not conformationally coupled along the chain or across the base pairs. Base motions are much smaller in magnitude than backbone motions. Base sliding allows imino N-H exchange, but it is localized, and only a small fraction of the N-H groups is exposed at any one time. Stacking and hydrogen bonding cause a rigid core of bases in the center of the molecule accounting for the hydrodynamic properties of DNA.