Institute for Solid State Theory and Center for Multiscale Theory and Computation, Westfälische-Wilhelms Universität Münster, Wilhelm-Klemm-Straße 10, 48149 Münster, Germany.
Institut für Anorganische und Analytische Chemie, Westfälische-Wilhelms Universität Münster, Corrensstraße 30, 48149 Münster, Germany.
Molecules. 2020 Oct 26;25(21):4942. doi: 10.3390/molecules25214942.
Quantum mechanical (QM) and hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations of a recently reported dinuclear mercury(II)-mediated base pair were performed aiming to analyse its intramolecular bonding pattern, its stability, and to obtain clues on the mechanism of the incorporation of mercury(II) into the DNA. The dynamic distance constraint was employed to find initial structures, control the dissociation process in an unbiased fashion and to determine the free energy required. A strong influence of the exocyclic carbonyl or amino groups of neighbouring base pairs on both the bonding pattern and the mechanism of incorporation was observed. During the dissociation simulation, an amino group of an adenine moiety of the adjacent base pair acts as a turnstile to rotate the mercury(II) ion out of the DNA core region. The calculations provide an important insight into the mechanism of formation of this dinuclear metal-mediated base pair and indicate that the exact location of a transition metal ion in a metal-mediated base pair may be more ambiguous than derived from simple model building.
对最近报道的双核汞(II)介导的碱基对进行了量子力学 (QM) 和混合量子力学/分子力学 (QM/MM) 分子动力学模拟，旨在分析其分子内键合模式、稳定性，并获得汞(II)掺入 DNA 机制的线索。采用动态距离约束来寻找初始结构，以无偏的方式控制解离过程，并确定所需的自由能。观察到相邻碱基对中环外羰基或氨基对键合模式和掺入机制的强烈影响。在解离模拟过程中，相邻碱基对中腺嘌呤部分的氨基基团充当转门，将汞(II)离子从 DNA 核心区域旋转出去。计算为这种双核金属介导的碱基对的形成机制提供了重要的见解，并表明金属介导的碱基对中过渡金属离子的确切位置可能比从简单的模型构建中得出的位置更模糊。
