Ma Ning, van der Vaart Arjan
Department of Chemistry, University of South Florida , 4202 East Fowler Avenue CHE 205, Tampa, Florida 33620, United States.
J Chem Inf Model. 2017 Aug 28;57(8):2020-2026. doi: 10.1021/acs.jcim.7b00215. Epub 2017 Jul 20.
Free energy simulations are presented to probe the energetic coupling between DNA bending and the flipping of a central thymine in double stranded DNA 13mers. The energetics are shown to depend on the neighboring base pairs, and upstream C or T or downstream C tended to make flipping more costly. Flipping to the major groove side was generally preferred. Bending aids flipping, by pushing the system up in free energy, but for small and intermediate bending angles the two were uncorrelated. At higher bending angles, bending and flipping became correlated, and bending primed the system for base flipping toward the major groove. Flipping of the 6-4 pyrimidine-pyrimidone and pyrimidine dimer photoproducts is shown to be more facile than for undamaged DNA. For the damages, major groove flipping was preferred, and DNA bending was much facilitated in the 6-4 pyrimidine-pyrimidone damaged system. Aspects of the calculations were verified by structural analyses of protein-DNA complexes with flipped bases.
我们进行了自由能模拟，以探究双链DNA 13聚体中DNA弯曲与中间胸腺嘧啶翻转之间的能量耦合。结果表明，能量学取决于相邻碱基对，上游的C或T以及下游的C往往会使翻转成本更高。通常更倾向于向大沟侧翻转。弯曲通过提高系统的自由能来辅助翻转，但对于小角度和中等角度的弯曲，二者不相关。在较大弯曲角度时，弯曲和翻转变得相关，并且弯曲使系统倾向于向大沟方向进行碱基翻转。结果表明，6-4嘧啶-嘧啶酮和嘧啶二聚体光产物的翻转比未受损的DNA更容易。对于这些损伤，更倾向于向大沟翻转，并且在6-4嘧啶-嘧啶酮受损系统中DNA弯曲得到了极大促进。通过对含有翻转碱基的蛋白质-DNA复合物进行结构分析，验证了计算的各个方面。
