Lyu Siying, Beiranvand Nassim, Freindorf Marek, Kraka Elfi
Computational and Theoretical Chemistry Group (CATCO), Department of Chemistry , Southern Methodist University , 3215 Daniel Ave , Dallas , Texas 75275-0314 , United States.
J Phys Chem A. 2019 Aug 15;123(32):7087-7103. doi: 10.1021/acs.jpca.9b05452. Epub 2019 Aug 5.
The Cremer-Pople ring puckering analysis and the Konkoli-Cremer local mode analysis supported by the topological analysis of the electron density were applied for the first comprehensive analysis of the interplay between deoxyribose ring puckering and intramolecular H-bonding in 2'-deoxycytidine, 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxyguanosine. We mapped for each deoxyribonucleoside the complete conformational energy surface and the corresponding pseudorotation path. We found only incomplete pseudorotation cycles, caused by ring inversion, which we coined as pseudolibration paths. On each pseudolibration path a global and a local minimum separated by a transition state were identified. The investigation of H-bond free deoxyribonucleoside analogs revealed that removal of the H-bond does not restore the full conformational flexibility of the sugar ring. Our work showed that ring puckering predominantly determines the conformational energy; the larger the puckering amplitude, the lower the conformational energy. In contrast no direct correlation between conformational energy and H-bond strength was found. The longest and weakest H-bonds are located in the local minimum region, whereas the shortest and strongest H-bonds are located outside the global and local minimum regions at the turning points of the pseudolibration paths, i.e., H-bonding determines the shape and length of the pseudolibration paths. In addition to the H-bond strength, we evaluated the covalent/electrostatic character of the H-bonds applying the Cremer-Kraka criterion of covalent bonding. H-bonding in the puric bases has a more covalent character whereas in the pyrimidic bases the H-bond character is more electrostatic. We investigated how the mutual orientation of the CHOH group and the base influences H-bond formation via two geometrical parameters describing the rotation of the substituents perpendicular to the sugar ring and their tilting relative to the ring center. According to our results, rotation is more important for H-bond formation. In addition we assessed the influence of the H-bond acceptor, the lone pair (N, respectively O), via the delocalization energy. We found larger delocalization energies corresponding to stronger H-bonds for the puric bases. The global minimum conformation of 2'-deoxyguanosine has the strongest H-bond of all conformers investigated in this work with a bond strength of 0.436 which is even stronger than the H-bond in the water dimer (0.360). The application of our new analysis to DNA deoxyribonucleotides and to unnatural base pairs, which have recently drawn a lot of attention, is in progress.
通过电子密度拓扑分析支持的克雷默 - 波普尔环皱分析和孔科利 - 克雷默局域模式分析，首次对2'-脱氧胞苷、2'-脱氧腺苷、2'-脱氧胸苷和2'-脱氧鸟苷中脱氧核糖环皱与分子内氢键之间的相互作用进行了全面分析。我们为每个脱氧核糖核苷绘制了完整的构象能量表面和相应的赝旋转路径。我们发现，由于环反转导致的赝旋转循环不完整，我们将其称为赝振动路径。在每条赝振动路径上，识别出一个由过渡态分隔的全局最小值和一个局部最小值。对无氢键的脱氧核糖核苷类似物的研究表明，去除氢键并不能恢复糖环的完全构象灵活性。我们的工作表明，环皱主要决定构象能量；皱折幅度越大，构象能量越低。相比之下，未发现构象能量与氢键强度之间存在直接相关性。最长且最弱的氢键位于局部最小值区域，而最短且最强的氢键位于赝振动路径转折点处的全局和局部最小值区域之外，即氢键决定了赝振动路径的形状和长度。除了氢键强度，我们还应用共价键的克雷默 - 克拉卡判据评估了氢键的共价/静电性质。嘌呤碱基中的氢键具有更强的共价性质，而嘧啶碱基中的氢键性质更具静电性。我们通过描述取代基垂直于糖环的旋转及其相对于环中心的倾斜的两个几何参数，研究了CHOH基团与碱基的相互取向如何影响氢键形成。根据我们的结果，旋转对氢键形成更为重要。此外，我们通过离域能评估了氢键受体孤对电子（分别为N或O）的影响。我们发现嘌呤碱基中对应更强氢键的离域能更大。在这项工作中研究的所有构象中，2'-脱氧鸟苷的全局最小构象具有最强的氢键，键强度为0.436，甚至比水二聚体中的氢键（0.360）更强。我们的新分析方法在DNA脱氧核苷酸和最近备受关注的非天然碱基对中的应用正在进行中。
