Base pair mismatches can erroneously be incorporated in the DNA. An adenine pairing with another adenine is one of the eight possible mismatches. The atomistic insights about the structure and dynamics of an A…A mismatch in a DNA (unbound form) is not yet accessible to any experimental technique. Earlier molecular dynamics (MD) simulations have shown that A…A mismatch in the midst of 5’CAG/3’GAC, 5’GAC/3’CAG and 5’CAA/3’GAT (underline represents the mismatch) are highly dynamic in nature. By employing MD simulation, the influence of an A...A mismatch in the midst of 5’GAA/3’CAT, 5’GAG/3’CAC, 5’AAC/3’TAG, 5’AAG/3’TAC, 5’TAA/3’AAT, 5’TAT/3’AAA and 5’AAT/3’TAA sequences have been investigated here. The results indicate that irrespective of the flanking sequences, the mismatch samples a variety of transient conformations, including a B-Z junction. Further, circular dichroism studies have been carried out to explore the ability of these sequences to bind with hZα_ADAR1 which specifically recognizes B-Z junction/Z-DNA. The results indicate that hZα_ADAR1 could not lead to a complete B to Z transition in the above sequences. Notably, a complete transition to Z-form has been reported earlier for 5’GAC/3’CAG upon titrating with hZα_ADAR1. Intriguingly, 5’AAC/3’TAG, 5’AAG/3’TAC and 5’GAA/3’CAT exhibit a B-Z junction formation rather than a complete transition to Z-form, similar to the situation of 5’CAA/3’GAT. These indicate that although A…A mismatch could induce a local B-Z junction transiently, hZα_ADAR1 requires the presence of a G…C/C…G base pair adjacent to the A…A mismatch for the binding. Additionally, the extent of B-Z junction has enhanced upon binding with hZα_ADAR1 in the presence of the A…A mismatch (specifically when CG, CA, AC, GA and AG steps occur), but not in the presence of the canonical base pairs. These confirm the inclination of A…A mismatch towards the B-Z junction.

碱基对错配可能会错误地掺入 DNA。腺嘌呤与另一个腺嘌呤配对是八种可能的错配之一。任何实验技术都无法获得关于 A…DNA 错配（未结合形式）的结构和动力学的原子学见解。早期分子动力学（MD）模拟已经表明，在...的5'C之中的不匹配甲G / 3'G甲C，5'G甲C / 3'C甲G和5'C甲A / 3' G A T（下划线代表不匹配）本质上是高度动态的。通过采用MD模拟，在5'G A A/3'C A T、5'G A G/3'C A中间A...A失配的影响C、5'A A C/3'T A G、5'A A G/3'T A C、5'T A A/3'A A T、5'T A T/3'A A A 和这里已经研究了5'A A T/3'T A A 序列。结果表明，无论侧翼序列如何，错配都会对各种瞬态构象进行采样，包括 BZ 连接。此外，已经进行了圆二色性研究以探索这些序列与特异性识别 BZ 连接/Z-DNA 的hZα _ADAR1结合的能力。结果表明 hZα _ADAR1无法在上述序列中导致完全的 B 到 Z 转换。值得注意的是，在用 hZα _ADAR1滴定后，5'G A C/3'C A G的完全转变为 Z 型。有趣的是，5'A A C/3'T A G、5'A A G/3'T A C 和 5'G A A/3'C A T 表现出 BZ 连接形成而不是完全过渡到 Z-形式，类似于 5'C A A/3'G A T的情况。这些表明虽然 A…A 错配会瞬时诱导局部 BZ 连接，但 hZα _ADAR1需要在 A...A 错配附近存在 G...C/C...G 碱基对以进行结合。此外，在存在 A…A 错配时（特别是当 CG、CA、AC、GA 和 AG 步骤发生时）与 hZα _ADAR1结合后，BZ 连接的程度有所增强，但在规范碱基对存在的情况下则不然。这些证实了 A…A 与 BZ 结不匹配的倾向。