Poater Jordi, Swart Marcel, Bickelhaupt F Matthias, Fonseca Guerra Célia
Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, VU University Amsterdam, De Boelelaan 1083, NL-1081 HV Amsterdam, The Netherlands. C.
Org Biomol Chem. 2014 Jul 14;12(26):4691-700. doi: 10.1039/c4ob00427b.
We have computationally investigated the structure and stability of B-DNA. To this end, we have analyzed the bonding in a series of 47 stacks consisting of two base pairs, in which the base pairs cover the full range of natural Watson-Crick pairs, mismatched pairs, and artificial DNA base pairs. Our analyses provide detailed insight into the role and relative importance of the various types of interactions, such as, hydrogen bonding, π-π stacking interactions, and solvation/desolvation. Furthermore, we have analyzed the functionality of the twist-angle on the stability of the structure. Interestingly, we can show that all stacked base pairs benefit from a stabilization by 6 to 12 kcal mol(-1) if stacked base pairs are twisted from 0° to 36°, that is, if they are mutually rotated from a congruent superposition to the mutually twisted stacking configuration that occurs in B-DNA. This holds especially for stacked AT pairs but also for other stacked base pairs, including GC. The electronic mechanism behind this preference for a twisted arrangement depends on the base pairs involved. We also show that so-called "diagonal interactions" (or cross terms) in the stacked base pairs are crucial for understanding the stability of B-DNA, in particular, in GC-rich sequences.
我们通过计算研究了B-DNA的结构和稳定性。为此，我们分析了一系列由两个碱基对组成的47个堆叠结构中的键合情况，其中碱基对涵盖了天然沃森-克里克对、错配碱基对和人工DNA碱基对的全范围。我们的分析深入洞察了各种相互作用的作用和相对重要性，例如氢键、π-π堆积相互作用以及溶剂化/去溶剂化。此外，我们分析了扭转角对结构稳定性的功能影响。有趣的是，我们可以表明，如果堆叠碱基对从0°扭转到36°，即从完全重叠相互旋转到B-DNA中出现的相互扭转堆叠构型，所有堆叠碱基对都会从6至12千卡摩尔⁻¹的稳定作用中受益。这尤其适用于堆叠的AT碱基对，但也适用于其他堆叠碱基对，包括GC。这种对扭转排列的偏好背后的电子机制取决于所涉及的碱基对。我们还表明，堆叠碱基对中的所谓“对角相互作用”（或交叉项）对于理解B-DNA的稳定性至关重要，特别是在富含GC的序列中。
