Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal
Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal
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DOI：
10.1261/rna.026658.111
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发表时间：
2011-12-01
期刊：
影响因子：
4.5
通讯作者：
Chen, Shi-Jie
中科院分区：
文献类型：
--
作者：
Cao, Song;Chen, Shi-Jie
我们开发了一个统计力学模型来预测RNA/RNA吻环复合物的结构和折叠稳定性。该理论的关键成分之一是RNA/RNA接吻复合物的构象熵。我们采用最近开发的基于虚拟键的RNA折叠模型（Vfold模型）来评估不同类型的接吻环的熵参数。对实验的基准测试表明，熵计算是可靠的。作为该模型的一个应用，我们应用该模型来研究HIV-1二聚化起始信号的接吻复合物的结构和折叠热力学。利用基于物理的能量参数，我们计算了HIV-1二聚体的自由能分布。从能量景观，我们确定了两个最小的自由能结构，这分别对应于接吻环二聚体和扩展双链体二聚体。结果支持HIV-1复制周期的两步二聚化过程。此外，基于Vfold模型和能量最小化，该理论可以预测天然结构以及自由能景观中的局部极小值。预测的接吻环二聚体和延伸双链体二聚体的均方根偏差（RMSD）类似于3.0埃。该方法为研究RNA/RNA接吻复合物提供了一种新的方法。
We develop a statistical mechanical model to predict the structure and folding stability of the RNA/RNA kissing-loop complex. One of the key ingredients of the theory is the conformational entropy for the RNA/RNA kissing complex. We employ the recently developed virtual bond-based RNA folding model (Vfold model) to evaluate the entropy parameters for the different types of kissing loops. A benchmark test against experiments suggests that the entropy calculation is reliable. As an application of the model, we apply the model to investigate the structure and folding thermodynamics for the kissing complex of the HIV-1 dimerization initiation signal. With the physics-based energetic parameters, we compute the free energy landscape for the HIV-1 dimer. From the energy landscape, we identify two minimal free energy structures, which correspond to the kissing-loop dimer and the extended-duplex dimer, respectively. The results support the two-step dimerization process for the HIV-1 replication cycle. Furthermore, based on the Vfold model and energy minimization, the theory can predict the native structure as well as the local minima in the free energy landscape. The root-mean-square deviations (RMSDs) for the predicted kissing-loop dimer and extended-duplex dimer are similar to 3.0 angstrom. The method developed here provides a new method to study the RNA/RNA kissing complex.