Lomzov Alexander A, Vorobjev Yury N, Pyshnyi Dmitrii V
Institute of Chemical Biology and Fundamental Medicine , Novosibirsk 630090, Russia.
Novosibirsk State University , Novosibirsk 630090, Russia.
J Phys Chem B. 2015 Dec 10;119(49):15221-34. doi: 10.1021/acs.jpcb.5b09645. Epub 2015 Nov 25.
A molecular dynamics simulation approach was applied for the prediction of the thermal stability of oligonucleotide duplexes. It was shown that the enthalpy of the DNA/DNA complex formation could be calculated using this approach. We have studied the influence of various simulation parameters on the secondary structure and the hybridization enthalpy value of Dickerson-Drew dodecamer. The optimal simulation parameters for the most reliable prediction of the enthalpy values were determined. The thermodynamic parameters (enthalpy and entropy changes) of a duplex formation were obtained experimentally for 305 oligonucleotides of various lengths and GC-content. The resulting database was studied with molecular dynamics (MD) simulation using the optimized simulation parameters. Gibbs free energy changes and the melting temperatures were evaluated using the experimental correlation between enthalpy and entropy changes of the duplex formation and the enthalpy values calculated by the MD simulation. The average errors in the predictions of enthalpy, the Gibbs free energy change, and the melting temperature of oligonucleotide complexes were 11%, 10%, and 4.4 °C, respectively. We have shown that the molecular dynamics simulation gives a possibility to calculate the thermal stability of native DNA/DNA complexes a priori with an unexpectedly high accuracy.
采用分子动力学模拟方法预测寡核苷酸双链体的热稳定性。结果表明，利用该方法可以计算DNA/DNA复合物形成的焓。我们研究了各种模拟参数对Dickerson-Drew十二聚体二级结构和杂交焓值的影响。确定了最可靠预测焓值的最佳模拟参数。通过实验获得了305种不同长度和GC含量的寡核苷酸双链体形成的热力学参数（焓变和熵变）。使用优化后的模拟参数，通过分子动力学（MD）模拟研究了所得数据库。利用双链体形成的焓变和熵变之间的实验相关性以及MD模拟计算得到的焓值，评估了吉布斯自由能变化和熔解温度。寡核苷酸复合物焓、吉布斯自由能变化和熔解温度预测的平均误差分别为11%、10%和4.4℃。我们已经表明，分子动力学模拟能够以前所未有的高精度先验计算天然DNA/DNA复合物的热稳定性。
