Department of Chemistry and Biochemistry and Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742, United States.
J Phys Chem B. 2013 May 2;117(17):4901-11. doi: 10.1021/jp401087x. Epub 2013 Apr 16.
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-Hückel 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 °C. Our model can be used to predict the folding thermodynamics for any RNA molecule in the presence of monovalent ions.
我们提出了一个热力学稳定的粗粒化模型，用于模拟单盐溶液中 RNA 的折叠。该模型包括堆积、氢键和静电相互作用作为描述 RNA 结构稳定性的基本组成部分。堆积相互作用使用一组核苷酸特异性参数进行参数化，这些参数是根据单碱基堆积和碱基对堆积的热力学测量值进行校准的。所有氢键都被假设具有相同的强度，而不论其在 RNA 结构中的位置如何。离子缓冲液通过反离子凝聚和 Debye-Hückel 理论的概念进行隐式建模。模型中的三个可调参数通过拟合两个 RNA 发夹和一个假结的实验数据来确定。一组参数可以在很宽的温度和盐浓度范围内很好地与三种 RNA 分子的热力学数据相吻合。在对模型进行校准的过程中，我们确定了单链 RNA 骨架上反离子凝聚的程度。减少的骨架电荷与离子强度无关，在 37°C 时为 RNA 裸电荷的 60%。我们的模型可用于预测单离子存在下任何 RNA 分子的折叠热力学。
