Blommers M J, Slot H J, van der Marel G A, van Boom J H, Hilbers C W
Laboratory of Biophysical Chemistry, University of Nijmegan, The Netherlands.
J Biomol Struct Dyn. 1990 Oct;8(2):233-51. doi: 10.1080/07391102.1990.10507804.
The conformational properties of the cyclic dinucleotide d less than pApA greater than were studied by means of molecular mechanics calculations in which a multiconformation analysis was combined with minimum energy calculations. In this approach models of possible conformers are built by varying the torsion angles of the molecule systematically. These models are then subjected to energy minimization; in the present investigation use was made of the AMBER Force field. It followed that the lowest energy conformer has a pseudo-two-fold axis of symmetry. In this conformer the deoxyribose sugars adopt a N-type conformation. The conformation of the sugar-phosphate backbone is determined by the following torsion angles: alpha +, beta t, gamma +, epsilon t and zeta +. The conformation of this ringsystem corresponds to the structure derived earlier by means of NMR spectroscopy and X-ray diffraction. The observation of a preference for N-type sugar conformations in this molecule can be explained by the steric hindrance induced between opposite H3' atoms when one sugar is switched from N- to S-type puckers. The sugars can in principle switch from N- to S-type conformations, but this requires at least the transition of gamma + to gamma -. In this process the molecule obtains an extended shape in which the bases switch from a pseudo-axial to a pseudo-equatorial position. The calculations demonstrate that, apart from the results obtained for the lowest energy conformation, the 180 degrees change in the propagation direction of the phosphate backbone can be achieved by several different combinations of the backbone torsion angles. It appeared that in the low energy conformers five higher order correlations are found. The combination of torsion angles which are involved in changes in the propagation direction of the sugar-phosphate backbone in DNA-hairpin loops and in tRNA, are found in the dataset obtained for cyclic d less than pApA greater than. It turns out, that in the available examples, 180 degrees changes in the backbone direction are localized between two adjacent nucleotides.
通过分子力学计算研究了环二核苷酸d小于pApA大于的构象性质，其中多构象分析与最低能量计算相结合。在这种方法中，通过系统地改变分子的扭转角来构建可能构象体的模型。然后对这些模型进行能量最小化；在本研究中使用了AMBER力场。结果表明，最低能量构象体具有一个伪二重对称轴。在这个构象体中，脱氧核糖糖采取N型构象。糖-磷酸主链的构象由以下扭转角决定：α+、βt、γ+、εt和ζ+。这个环系统的构象与早期通过核磁共振光谱和X射线衍射得到的结构相对应。在这个分子中观察到对N型糖构象的偏好可以通过当一个糖从N型向S型褶皱转变时在相对的H3'原子之间引起的空间位阻来解释。糖原则上可以从N型构象转变为S型构象，但这至少需要γ+向γ-的转变。在这个过程中，分子获得一个伸展的形状，其中碱基从伪轴向位置转变为伪赤道位置。计算表明，除了最低能量构象的结果外，磷酸主链传播方向的180度变化可以通过主链扭转角的几种不同组合来实现。结果发现，在低能量构象体中存在五个高阶相关性。在DNA发夹环和tRNA中参与糖-磷酸主链传播方向变化的扭转角组合，在环d小于pApA大于的数据集里被发现。结果表明，在现有例子中，主链方向的180度变化位于两个相邻核苷酸之间。
