Veritas In Silico, 1-11-1 Nishigotanda, Shinagawa-ku, Tokyo 141-0031, Japan.
Department of Life Science, Faculty of Advanced Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino-shi, Chiba 275-0016, Japan.
Int J Mol Sci. 2021 Sep 8;22(18):9708. doi: 10.3390/ijms22189708.
For the last 20 years, it has been common lore that the free energy of RNA duplexes formed from canonical Watson-Crick base pairs (bps) can be largely approximated with dinucleotide bp parameters and a few simple corrective constants that are duplex independent. Additionally, the standard benchmark set of duplexes used to generate the parameters were GC-rich in the shorter duplexes and AU-rich in the longer duplexes, and the length of the majority of the duplexes ranged between 6 and 8 bps. We were curious if other models would generate similar results and whether adding longer duplexes of 17 bps would affect the conclusions. We developed a gradient-descent fitting program for obtaining free-energy parameters-the changes in Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS), and the melting temperature (Tm)-directly from the experimental melting curves. Using gradient descent and a genetic algorithm, the duplex melting results were combined with the standard benchmark data to obtain bp parameters. Both the standard (Turner) model and a new model that includes length-dependent terms were tested. Both models could fit the standard benchmark data; however, the new model could handle longer sequences better. We developed an updated strategy for fitting the duplex melting data.
在过去的 20 年中，人们普遍认为，由规范的沃森-克里克碱基对 (bp) 形成的 RNA 双链的自由能可以通过二核苷酸 bp 参数和几个独立于双链的简单修正常数来大致近似。此外，用于生成参数的标准双链基准集在较短的双链中富含 GC，在较长的双链中富含 AU，并且大多数双链的长度在 6 到 8 bp 之间。我们很好奇其他模型是否会产生类似的结果，以及添加 17 bp 的更长双链是否会影响结论。我们开发了一个梯度下降拟合程序，用于直接从实验熔解曲线获得自由能参数——吉布斯自由能 (ΔG)、焓 (ΔH) 和熵 (ΔS) 的变化，以及熔解温度 (Tm)。使用梯度下降和遗传算法，将双链熔解结果与标准基准数据相结合，以获得 bp 参数。我们测试了标准（特纳）模型和包含长度相关项的新模型。两个模型都可以拟合标准基准数据；然而，新模型可以更好地处理更长的序列。我们开发了一种更新的拟合双链熔解数据的策略。
