Loop-loop interaction in an adenine-sensing riboswitch: a molecular dynamics study.
Loop-loop interaction in an adenine-sensing riboswitch: a molecular dynamics study.
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DOI：
10.1261/rna.037549.112
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Villa A
中科院分区：
文献类型：
--
作者：
Allnér O;Nilsson L;Villa A
利用全原子分子动力学方法模拟了腺嘌呤敏感加A-核糖开关，研究了适配体结构中的关键三级元件--接吻环的断裂。在所有的模拟系统中观察到一个两步过程。首先看到堆积和氢键相互作用的一般损失。接合区域在形成吻接环之前部分组织化，并且一个残基A24将环螺旋锚定在一起。核糖开关是基于mRNA的分子，能够控制基因的表达。它们在配体结合时经历构象变化，并且因此，它们抑制或促进相关基因的表达。结构重排和功能之间的密切联系使得详细了解分子相互作用是理解核糖开关机制和效率的重要一步。我们进行了全原子分子动力学模拟的腺嘌呤传感添加A-核糖开关研究的接吻环，在适体结构的一个关键的三级元素的断裂。我们研究了与其同源配体复合以及在不存在配体的情况下的add A-核糖开关的适体结构域。发夹的打开使用伞采样，使用两个环之间的距离作为反应坐标来模拟。在所有的模拟系统中观察到一个两步过程。首先，看到堆叠和氢键相互作用的一般损失。最后断裂的相互作用是两个碱基对G37-C61和G38-C60，但断裂不影响能量分布，表明它们在三级结构形成中起关键作用，但在结构稳定中不起作用。接合区在形成对接环之前部分组织化，残基A24将环螺旋锚定在一起。此外，当环之间的距离增加时，其中一个发夹通过改变其在结构中的取向而显示出更大的灵活性，而另一个发夹保持其与结构的其余部分的同轴布置。
All-atom molecular dynamics simulations of the adenine-sensing add A-riboswitch to study the breaking of the kissing loop, a key tertiary element in the aptamer structure, were performed. A two-step process was observed in all the simulated systems. A general loss of stacking and hydrogen bond interactions is first seen. The junction area is partially organized before the kissing loop formation and one residue, A24, anchors together the loop helices. Riboswitches are mRNA-based molecules capable of controlling the expression of genes. They undergo conformational changes upon ligand binding, and as a result, they inhibit or promote the expression of the associated gene. The close connection between structural rearrangement and function makes a detailed knowledge of the molecular interactions an important step to understand the riboswitch mechanism and efficiency. We have performed all-atom molecular dynamics simulations of the adenine-sensing add A-riboswitch to study the breaking of the kissing loop, one key tertiary element in the aptamer structure. We investigated the aptamer domain of the add A-riboswitch in complex with its cognate ligand and in the absence of the ligand. The opening of the hairpins was simulated using umbrella sampling using the distance between two loops as the reaction coordinate. A two-step process was observed in all the simulated systems. First, a general loss of stacking and hydrogen bond interactions is seen. The last interactions that break are the two base pairs G37-C61 and G38-C60, but the break does not affect the energy profile, indicating their pivotal role in the tertiary structure formation but not in the structure stabilization. The junction area is partially organized before the kissing loop formation and residue A24 anchors together the loop helices. Moreover, when the distance between the loops is increased, one of the hairpins showed more flexibility by changing its orientation in the structure, while the other conserved its coaxial arrangement with the rest of the structure.
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影响因子：
4.1
作者：
Lee ER;Blount KF;Breaker RR
通讯作者：
Breaker RR
DOI：
10.1002/prot.340040208
发表时间：
1988-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
BRUNGER, AT;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
5.6
作者：
LEE, B;RICHARDS, FM
通讯作者：
RICHARDS, FM
影响因子：
6.1
作者：
Batey, Robert T.
通讯作者：
Batey, Robert T.
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M