Coarse-Grained Model for Predicting RNA Folding Thermodynamics
Coarse-Grained Model for Predicting RNA Folding Thermodynamics
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DOI：
10.1021/jp401087x
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发表时间：
2013-05-02
影响因子：
3.3
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
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作者：
Denesyuk, Natalia A.;Thirumalai, D.
我们提出了一个热力学稳健的粗粒度模型来模拟RNA在单价盐溶液中的折叠。该模型将堆积、氢键和静电相互作用作为描述RNA结构稳定性的基本成分。使用一组核苷酸特定参数来参数化堆积相互作用，这些参数是根据单碱基堆栈和碱基对堆栈的热力学测量进行校准的。所有的氢键都被认为具有相同的强度，无论它们在RNA结构中的背景如何。利用反离子凝聚的概念和德拜-休克尔理论，对离子缓冲液进行了隐式建模。通过对两个RNA发夹和一个假结的实验数据进行拟合，确定了模型中的三个可调参数。一组参数与三个RNA分子在广泛的温度和盐浓度范围内的热力学数据提供了很好的一致性。在校准模型的过程中，我们确定了反离子在单链RNA骨架上的缩合程度。还原的主链电荷与离子强度无关，是37℃时RNA裸电荷的60%。我们的模型可以用来预测任何RNA分子在单价离子存在下的折叠热力学。
We present a thermodynamically robust coarse, grained model to simulate folding of RNA in monovalent salt solutions. The model includes stacking, hydrogen bond, and electrostatic interactions as fundamental components in describing the stability of RNA structures. The stacking interactions are parametrized using a set of nucleotide specific parameters, which were calibrated against the thermodynamic measurements for single base stacks and base pair stacks. All hydrogen bonds are assumed to have the same strength, regardless of their context in the RNA structure. The ionic buffer is modeled implicitly, using the concept of counterion condensation and the Debye-Huckel theory. The three adjustable Parameters in the model were determined by fitting the experimental data for two RNA hairpins and a pseudoknot. A single set of parameters provides good agreement with thermodynamic data for the three RNA molecules over a wide range of temperatures and salt concentrations. In the process of calibrating the model, we establish the extent of counterion condensation onto the single stranded RNA backbone. The reduced backbone charge is independent of the ionic strength and is 60% of the RNA bare charge at 37 degrees C. Our model can be used to predict the folding thermodynamics for any RNA molecule in the presence of monovalent ions.