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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Dynamics and stability of GCAA tetraloops with 2-aminopurine and purine substitutions.
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Dynamics and stability of GCAA tetraloops with 2-aminopurine and purine substitutions.

机译：具有2-氨基嘌呤和嘌呤取代的GCAA四环的动力学和稳定性。

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摘要

The contributions of various interactions in the GGCGCAAGCC hairpin containing a GCAA tetraloop were studied by computer simulations using the substitutions of functional groups. The guanosine (G) in the first tetraloop position or in the C-G closing base pair was replaced by 2-aminopurine (AP), and the individual tetraloop's adenosines (A) were replaced by purine (PUR). These substitutions eliminated particular hydrogen bonds thought to stabilize the GCAA tetraloop. For each substitution, molecular dynamics (MD) simulations were carried out in an aqueous solution with sodium counterions, using the CHARMM27 force field. The MD simulations showed that the substitutions in the first (G-->AP) and the third (A-->PUR) position of the GCAA tetraloop did not significantly influence the conformation of the hairpin. A long-lived bridging water molecule observed in the GCAA loop was present in both modified loops. The substitutions made in the last loop position (A-->PUR) or in the C-G base pair closing the tetraloop (G-->AP) to some extent influenced the loop structure and dynamics. These loops did not display the long-lived bridging water molecules. When the second A in the GCAA loop was replaced by PUR, the first A in the loop was observed in the anti or in the syn orientation about the glycosyl bond. The G to AP substitution in C-G base pair led to a change of their arrangement from the Watson-Crick to wobble. The MD simulations of the hairpin with C-AP wobble closing base pair showed increased conformational dynamics of the hairpin. The changes of hairpin formation free energy associated with the substitutions of individual bases were calculated by the free energy perturbation method. Our theoretical estimates suggest a larger destabilization for the G to AP substitutions in GCAA loop than for the substitutions of individual A's by PUR, which is in accordance with experimental tendency. The calculations predicted a similar free energy change for G to AP substitutions in the GCAA tetraloop and in the C-G closing base pair.
机译：通过使用官能团取代的计算机模拟研究了包含GCAA四环的GGCGCAAGCC发夹中各种相互作用的贡献。在第一个四环位置或C-G闭合碱基对中的鸟嘌呤（G）被2-氨基嘌呤（AP）取代，单个四环的腺苷（A）被嘌呤（PUR）取代。这些取代消除了特定的氢键，这些氢键被认为可以稳定GCAA四环。对于每个取代，使用CHARMM27力场在带有钠抗衡离子的水溶液中进行分子动力学（MD）模拟。 MD模拟显示，GCAA四环的第一个（G-> AP）和第三个（A-> PUR）位置的取代不会显着影响发夹的构象。在两个修饰的环中均存在在GCAA环中观察到的长寿命桥接水分子。在最后一个环位置（A-> PUR）或在封闭四环的C-G碱基对中进行的取代（G-> AP）在一定程度上影响了环的结构和动力学。这些回路没有显示长寿命的桥连水分子。当GCAA环中的第二个A被PUR取代时，观察到环中的第一个A处于糖基键的反方向或同向。 C-G碱基对中的G到AP取代导致其排列方式从沃森克里克变为摇摆。具有C-AP摆动闭合碱基对的发夹的MD模拟显示出发夹的构象动力学增加。通过自由能扰动法计算了与单个碱基取代相关的发夹形成自由能的变化。我们的理论估计表明，GCAA环中G取代AP的失稳大于PUR取代单个A的失稳，这符合实验趋势。计算结果预测，在GCAA四环和C-G封闭碱基对中，G取代AP的自由能类似。

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