School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
Phys Chem Chem Phys. 2021 Apr 14;23(14):8891-8899. doi: 10.1039/d0cp06630c. Epub 2021 Apr 6.
GC content is a contributing factor to the stability of nucleic acids due to hydrogen bonding. More hydrogen bonding generally results in greater stability. Empirical evidence, however, has suggested that the GC content of a nucleic acid is a poor predictor of its stability, implying that there are sequence-dependent interactions besides what its GC content indicates. To examine how much such sequence-dependent interactions affect the interaction energies of double-stranded DNA (dsDNA) molecules, dsDNA molecules of different sequences are generated and examined in silico for variabilities in the interaction energies within each group of dsDNA molecules of the same GC content. Since the amount of hydrogen bonding depends on the GC content, holding the GC content fixed when examining the differences in interaction energies allows sequence-dependent interactions to be isolated. The nature of sequence-dependent interactions is then dissected using energy decomposition analysis (EDA). By using EDA, the components of the interactions that depend on the neighboring base pairs help explain some of the variability in the interaction energies of the dsDNA molecules despite having the same GC content. This work provides a new paradigm and tool for the study and analysis of the distributions of interaction components in dsDNA with the same GC content using EDA within large-scale quantum chemistry calculations.
GC 含量是由于氢键而导致核酸稳定性的一个影响因素。通常，更多的氢键会导致更大的稳定性。然而，经验证据表明，核酸的 GC 含量是其稳定性的一个较差预测因子，这意味着除了 GC 含量所表明的序列依赖性相互作用之外，还有其他序列依赖性相互作用。为了研究这种序列依赖性相互作用对双链 DNA（dsDNA）分子的相互作用能有多大影响，生成了不同序列的 dsDNA 分子，并在计算机上对具有相同 GC 含量的每一组 dsDNA 分子内的相互作用能的可变性进行了检查。由于氢键的数量取决于 GC 含量，因此在检查相互作用能的差异时固定 GC 含量可以分离出序列依赖性相互作用。然后使用能量分解分析（EDA）来剖析序列依赖性相互作用的性质。通过使用 EDA，可以帮助解释尽管具有相同的 GC 含量，但 dsDNA 分子相互作用能存在一些可变性的原因，这些原因取决于相邻的碱基对。这项工作为使用 EDA 在大规模量子化学计算中研究和分析具有相同 GC 含量的 dsDNA 中相互作用成分的分布提供了一个新的范例和工具。
