通过 DPT：QM 和 QTAIM 计算方法对 C·T 错配 DNA 碱基对互变异构的原子水平理解。
Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches.
机构信息
Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotnoho Str., Kyiv, 03680, Ukraine; Research and Educational Center, State Key Laboratory of Molecular and Cell Biology, 150 Zabolotnoho Str., Kyiv, 03680, Ukraine; Department of Molecular Biotechnology and Bioinformatics, Institute of High Technologies, Taras Shevchenko National University of Kyiv, 2 Hlushkova Ave., Kyiv, 03022, Ukraine.
出版信息
J Comput Chem. 2013 Nov 15;34(30):2577-90. doi: 10.1002/jcc.23412. Epub 2013 Aug 16.
It was established that the cytosine·thymine (C·T) mismatched DNA base pair with cis-oriented N1H glycosidic bonds has propeller-like structure (|N3C4C4N3| = 38.4°), which is stabilized by three specific intermolecular interactions-two antiparallel N4H…O4 (5.19 kcal mol(-1)) and N3H…N3 (6.33 kcal mol(-1)) H-bonds and a van der Waals (vdW) contact O2…O2 (0.32 kcal mol(-1)). The C·T base mispair is thermodynamically stable structure (ΔG(int) = -1.54 kcal mol(-1) ) and even slightly more stable than the A·T Watson-Crick DNA base pair (ΔG(int) = -1.43 kcal mol(-1)) at the room temperature. It was shown that the C·T ↔ C*·T* tautomerization via the double proton transfer (DPT) is assisted by the O2…O2 vdW contact along the entire range of the intrinsic reaction coordinate (IRC). The positive value of the Grunenberg's compliance constants (31.186, 30.265, and 22.166 Å/mdyn for the C·T, C*·T*, and TS(C·T ↔ C*·T*), respectively) proves that the O2…O2 vdW contact is a stabilizing interaction. Based on the sweeps of the H-bond energies, it was found that the N4H…O4/O4H…N4, and N3H…N3 H-bonds in the C·T and C*·T* base pairs are anticooperative and weaken each other, whereas the middle N3H…N3 H-bond and the O2…O2 vdW contact are cooperative and mutually reinforce each other. It was found that the tautomerization of the C·T base mispair through the DPT is concerted and asynchronous reaction that proceeds via the TS(C·T ↔ C*·T*) stabilized by the loosened N4-H-O4 covalent bridge, N3H…N3 H-bond (9.67 kcal mol(-1) ) and O2…O2 vdW contact (0.41 kcal mol(-1) ). The nine key points, describing the evolution of the C·T ↔ C*·T* tautomerization via the DPT, were detected and completely investigated along the IRC. The C*·T* mispair was revealed to be the dynamically unstable structure with a lifetime 2.13·× 10(-13) s. In this case, as for the A·T Watson-Crick DNA base pair, activates the mechanism of the quantum protection of the C·T DNA base mispair from its spontaneous mutagenic tautomerization through the DPT.
已经确定，具有顺式 N1H 糖苷键的胞嘧啶-胸腺嘧啶（C·T）错配 DNA 碱基对具有类似推进器的结构（|N3C4C4N3|=38.4°），该结构由三个特定的分子间相互作用稳定：两个反平行的 N4H…O4（5.19 kcal mol(-1)）和 N3H…N3（6.33 kcal mol(-1)）氢键和范德华（vdW）接触 O2…O2（0.32 kcal mol(-1)）。C·T 碱基错配是热力学稳定的结构（ΔG(int)=-1.54 kcal mol(-1)），甚至比室温下的 A·T Watson-Crick DNA 碱基对（ΔG(int)=-1.43 kcal mol(-1)）略稳定。已经表明，C·T↔C*·T互变异构通过双质子转移（DPT）辅助沿着整个内禀反应坐标（IRC）的 O2…O2 vdW 接触。Grunenberg 顺应常数的正值（C·T、C·T和 TS(C·T↔C·T*)的分别为 31.186、30.265 和 22.166 Å/mdyn）证明了 O2…O2 vdW 接触是一种稳定的相互作用。基于氢键能量的扫描，发现 C·T 和 C*·T碱基对中的 N4H…O4/O4H…N4 和 N3H…N3 氢键是反协同的，彼此削弱，而中间的 N3H…N3 氢键和 O2…O2 vdW 接触是协同的，相互加强。已经发现，C·T 碱基错配通过 DPT 的互变异构是协同的、异步反应，通过由松散的 N4-H-O4 共价桥、N3H…N3 氢键（9.67 kcal mol(-1)）和 O2…O2 vdW 接触（0.41 kcal mol(-1)）稳定的 TS(C·T↔C·T*)进行。沿着 IRC，检测并完全研究了描述通过 DPT 进行 C·T↔C*·T互变异构的九个关键点。发现 C·T*错配是动态不稳定的结构，寿命为 2.13·×10(-13) s。在这种情况下，对于 A·T Watson-Crick DNA 碱基对，通过 DPT 激活量子保护 C·T DNA 碱基错配免于自发突变互变异构的机制。
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