Atomistic simulation of the DNA helix-coil transition.
Atomistic simulation of the DNA helix-coil transition.
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DNA 螺旋-螺旋转变的原子模拟。
DOI：
10.1021/jp0756552
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
S. Piana
中科院分区：
文献类型：
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作者：
S. Piana
螺旋到线圈的转变，或 DNA 熔化，是生命的基本过程之一。然而，利用当前的光谱技术很难对溶液中的该反应进行原子描述。另一方面，DNA 熔化的计算机模拟对理论化学家提出了巨大的挑战，因为即使对于短序列，该过程在自然界中也会以毫秒或更长时间尺度发生。因此，这种类型的模拟尚未尝试过，并且力场再现 DNA 杂交自由能的准确性尚不清楚。这里展示了如何通过结合复制品交换和元动力学，可以在室温下模拟 DNA 六聚体的螺旋到卷曲的转变，并表征反应中间体和杂交的相对自由能。使用标准 Amber99 力场和修改磷酸盐扭转参数的版本研究了三个序列 [Peres, A.;等人。生物物理学。 J. 2007, 92, 3817-3829]。结果表明，Amber99 力场高估了单链和非规范 DNA 的稳定性，预计这些 DNA 在热力学上比规范 B-DNA 更稳定。因此，这种力场不适合发生较大构象变化的 DNA 研究。佩雷斯等人引入的变化。显着提高与实验的一致性。然而，所研究的序列之一的稳定性仍然被修改后的力场低估。结论是，虽然当前的力场可以提供杂交反应的合理图像，但可能需要极化力场才能与实验的杂交自由能获得更定量的一致性。
The helix to coil transition, or DNA melting, is one of the fundamental processes of life. Nevertheless, it is difficult to achieve an atomistic description of this reaction in solution with current spectroscopic techniques. On the other hand, the computer simulation of DNA melting poses a formidable challenge for theoretical chemists as, even for short sequences, the process occurs in nature on the millisecond or longer time scale. For this reason, this type of simulation has not been attempted yet and the accuracy of force fields in reproducing the free energy of DNA hybridization is not known. Here it is shown how, by combining replica exchange and metadynamics, it is possible to simulate the helix to coil transition of DNA hexamers at room temperature and characterize the reaction intermediates and the relative free energy of hybridization. Three sequences were investigated with both the standard Amber99 force field and a version with modified phosphate torsion parameters [Peres, A.; et al. Biophys. J. 2007, 92, 3817-3829]. It is shown that the Amber99 force field overestimates the stability of single stranded and noncanonical DNA that are predicted to be thermodynamically more stable than canonical B-DNA. Therefore this force field is not suitable for DNA studies where large conformational changes occur. The changes introduced by Peres et al. significantly improve the agreement with the experiment. However, the stability of one of the sequences investigated is still underestimated by the modified force field. It is concludes that, although current force fields can provide a reasonable picture of the hybridization reaction, a polarizable force field may be required to obtain a more quantitative agreement with the experimental free energies of hybridization.