Computational Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India; Homi Bhaba National Institute, Anushaktinagar, Mumbai 400094, India.
Computational Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
Biochim Biophys Acta Gen Subj. 2020 Jul;1864(7):129600. doi: 10.1016/j.bbagen.2020.129600. Epub 2020 Mar 14.
Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The A:A w:wC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Its effect is pronounced when the A:A w:wC basepair stacks on Sheared wobble G:U W:WC basepairs.
We employed molecular dynamics simulations of three possible double helices with GAG, UAG and GAU sequence motifs at their centers and quantum chemical calculation for non-canonical A:A w:wC basepair stacked on G:U W:WC basepair.
We noticed stable structures of GAG motif with specifically negative Shear of the A:A basepair but stabilities of the other motifs were not found with A:A w:wC basepairing. Hybrid DFT-D and MP2 stacking energy analyses on dinucleotide step sequences, A:A w:wC::G:U W:WC and A:A w:wC::U:G W:WC reveal that viable orientation of A:A::G:U prefers one of the H-bonding modes with negative Shear, supported by crystal structure database. The A:A::U:G dinucleotide, however, prefers structure with only positive Shear.
The quantum chemical calculations explain why MD simulations of GAG sequence motif only appear stable. In the cases of the GAU and UAG motifs "tug of war" situation between positive and negative Shears of A:A w:wC basepair induces conformational plasticity.
We have projected comprehensive reason behind the promiscuous nature of A:A w:wC basepair which brings occasional structural plasticity.
使用从晶体结构数据库获得的碱基对参数最可能值，可以对 RNA 双链体进行分子建模。涉及顺式取向的两个腺嘌呤的 Watson-Crick 边缘的 A:A w:wC 非规范碱基对在数据库中出现得相当频繁。由于两种不同的氢键结合方案，其剪切的双峰分布导致在分配最可能值时出现混淆。当 A:A w:wC 碱基对在剪切摆动的 G:U W:WC 碱基对上堆积时，其效果更为明显。
我们在中心具有 GAG、UAG 和 GAU 序列基序的三个可能的双链体上进行了分子动力学模拟，并对 G:U W:WC 碱基对上堆积的非规范 A:A w:wC 碱基对进行了量子化学计算。
我们注意到 GAG 基序具有特定的负剪切 A:A 碱基对的稳定结构，但其他基序没有发现 A:A w:wC 碱基配对的稳定性。二核苷酸步序列 A:A w:wC::G:U W:WC 和 A:A w:wC::U:G W:WC 的杂交 DFT-D 和 MP2 堆积能分析表明，可行的 A:A::G:U 取向倾向于具有负剪切的氢键结合模式之一，这得到了晶体结构数据库的支持。然而，A:A::U:G 二核苷酸更喜欢只有正剪切的结构。
量子化学计算解释了为什么只有 GAG 序列基序的 MD 模拟才显示出稳定性。在 GAU 和 UAG 基序的情况下，A:A w:wC 碱基对的正剪切和负剪切之间的“拔河”情况导致构象可塑性。
我们预测了 A:A w:wC 碱基对混杂性质背后的综合原因，这种性质偶尔会带来结构可塑性。
