Hydration Waters Make Up for the Missing Third Hydrogen Bond in the A·T Base Pair

IF 3.7 Q2 CHEMISTRY, PHYSICAL

ACS Physical Chemistry Au Pub Date : 2024-01-24 DOI:10.1021/acsphyschemau.3c00058

Chi H. Mak*,

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Abstract

Base pairing complementarity is central to DNA function. G·C and A·T pair specificity is thought to originate from the different number of hydrogen bonds the pairs make. Quantifying how many hydrogen bonds exist can be difficult because water molecules in the surrounding can make up for or disrupt direct hydrogen bonds, and the hydration structures around A·T and G·C pairs on duplex DNA are distinct. Large-scale computer simulations have been used here to create a detailed map for the hydration structure on A·T and G·C base pairs in water. The contributions of specific hydration waters to the free energy of each of the hydrogen bonds in the A·T and G·C pairs were computed. Using the equilibrium fractions of hydrated versus unhydrated states from the hydration profiles, the impact of specific bound waters on each hydrogen bond can be uniquely quantified using a thermodynamic construction. The findings suggest that hydration water in the minor groove of an A·T pair can provide up to about 2 kcal/mol of free energy advantage, effectively making up for the missing third hydrogen bond in the A·T pair compared to G·C, rendering the intrinsic thermodynamic stability of the A·T pair almost synonymous with G·C.

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水合作用弥补 A-T 碱基对中缺失的第三个氢键

碱基配对互补性是 DNA 功能的核心。G-C和A-T配对的特异性被认为源于这两个配对所产生的氢键数量不同。由于周围的水分子可以弥补或破坏直接氢键，而且双链DNA上A-T和G-C配对周围的水合结构各不相同，因此很难量化氢键的数量。本文利用大规模计算机模拟绘制了 A-T 和 G-C 碱基对在水中水合结构的详细图谱。计算了特定水合水对 A-T 和 G-C 碱基对中每个氢键自由能的贡献。利用水合曲线中水合状态与非水合状态的平衡分数，可以通过热力学结构唯一量化特定结合水对每个氢键的影响。研究结果表明，A-T 对小凹槽中的水合水可以提供高达约 2 kcal/mol 的自由能优势，有效弥补了 A-T 对中比 G-C 少的第三个氢键，使 A-T 对的内在热力学稳定性几乎与 G-C 相同。

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来源期刊

ACS Physical Chemistry Au 物理化学-

CiteScore

3.70

自引率

0.00%

发文量

期刊介绍： ACS Physical Chemistry Au is an open access journal which publishes original fundamental and applied research on all aspects of physical chemistry. The journal publishes new and original experimental computational and theoretical research of interest to physical chemists biophysical chemists chemical physicists physicists material scientists and engineers. An essential criterion for acceptance is that the manuscript provides new physical insight or develops new tools and methods of general interest. Some major topical areas include:Molecules Clusters and Aerosols; Biophysics Biomaterials Liquids and Soft Matter; Energy Materials and Catalysis