Miller J L, Kollman P A
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, 94143-0446, USA.
J Mol Biol. 1997 Jul 18;270(3):436-50. doi: 10.1006/jmbi.1997.1113.
We report on the results of five independent and unrestrained molecular dynamics simulations of an RNA tetraloop, r(GGACUUCGGUCC), and its related structures with the loop UUCG sugars changed to deoxyribose. Two separate NMR structures have been reported for the loop portion of this molecule, with the second refinement resulting in a slightly different and more accurate conformation for the loop. The root-mean-square deviation (RMSd) between the two NMR structures, for the loop portions only, is 2.5 A. Our simulations, starting from the two NMR structures, demonstrate that this tetraloop is a very stable and rigid structure with both nanosecond length simulations staying very close to the initial structures. Additionally, both simulations preserved most, if not all, of the NMR-derived interactions and violated very few of the nuclear Overhauser effect (NOE)-derived distances used in the structure refinements. However, when the two NMR structures were simulated with deoxyriboses in the loops instead of the native riboses, the flexibility of the systems increased and we observed a conversion from the incorrect to the correct loop conformation in the simulation which started in the incorrect loop conformation. When the riboses were subsequently re-introduced back into the structure which underwent the conversion, the agreement between this simulation and the one starting from the correct NMR structure was a remarkably low 0.5 A, demonstrating an almost complete convergence from the incorrect to the correct structure using unrestrained molecular dynamics.
我们报告了对RNA四环r(GGACUUCGGUCC)及其相关结构进行的五次独立且无约束的分子动力学模拟结果，其中环上的UUCG糖被替换为脱氧核糖。对于该分子的环部分，已经报道了两个独立的NMR结构，第二次优化得到了环的一个略有不同且更精确的构象。仅对于环部分，两个NMR结构之间的均方根偏差（RMSd）为2.5 Å。我们从这两个NMR结构开始进行模拟，结果表明这个四环是一个非常稳定且刚性的结构，两次纳秒时长的模拟都与初始结构非常接近。此外，两次模拟都保留了大部分（如果不是全部的话）源自NMR的相互作用，并且在结构优化中违反的源自核Overhauser效应（NOE）的距离非常少。然而，当在环中用脱氧核糖而非天然核糖对这两个NMR结构进行模拟时，系统的灵活性增加，并且我们在从错误环构象开始的模拟中观察到从错误环构象向正确环构象的转变。当随后将核糖重新引入经历了转变的结构中时，该模拟与从正确NMR结构开始的模拟之间的一致性低至显著的0.5 Å，这表明使用无约束分子动力学从错误结构到正确结构几乎完全收敛。
