Department of Physics, University of Surrey, Guildford GU2 7XH, U.K.
Leverhulme Quantum Biology Doctoral Training Centre, University of Surrey, Guildford GU2 7XH, U.K.
J Phys Chem B. 2023 May 18;127(19):4220-4228. doi: 10.1021/acs.jpcb.2c08631. Epub 2023 Mar 20.
The adenine-thymine tautomer (A*-T*) has previously been discounted as a spontaneous mutagenesis mechanism due to the energetic instability of the tautomeric configuration. We study the stability of A*-T* while the nucleobases undergo DNA strand separation. Our calculations indicate an increase in the stability of A*-T* as the DNA strands unzip and the hydrogen bonds between the bases stretch. Molecular Dynamics simulations reveal the time scales and dynamics of DNA strand separation and the statistical ensemble of opening angles present in a biological environment. Our results demonstrate that the unwinding of DNA, an inherently out-of-equilibrium process facilitated by helicase, will change the energy landscape of the adenine-thymine tautomerization reaction. We propose that DNA strand separation allows the stable tautomerization of adenine-thymine, providing a feasible pathway for genetic point mutations via proton transfer between the A-T bases.
腺嘌呤-胸腺嘧啶互变异构体（A*-T*）以前由于互变异构构型的能量不稳定性而被排除为自发突变机制。我们研究了在核苷酸碱基经历 DNA 链分离时 A*-T的稳定性。我们的计算表明，随着 DNA 链解旋，碱基之间的氢键拉伸，A-T*的稳定性增加。分子动力学模拟揭示了 DNA 链分离的时间尺度和动力学以及生物环境中存在的开口角度的统计集合。我们的结果表明，DNA 的解旋，即解旋酶促进的固有非平衡过程，将改变腺嘌呤-胸腺嘧啶互变异构反应的能量景观。我们提出，DNA 链分离允许腺嘌呤-胸腺嘧啶的稳定互变异构，通过 A-T 碱基之间的质子转移为遗传点突变提供了可行的途径。
