Modeling RNA secondary structures with explicit loop free energies

我们最近扩展了预测RNA二级结构的现有理论框架，以便在多项式计算时间内明确考虑任意拓扑的多环的任意环自由能（T. R. Einert et al., PRL 101, 048103(2008)）。熔化曲线和温度与实验结果一致。此外，接触副概率和力扩展曲线在我们的形式中很容易得到。所有的结果都对热力学环建模的细节非常敏感，即使是相对较短的RNA序列。在本提案中，我们计划进一步扩展形式主义，并将其应用于一些生物学相关的情况，如盐效应，配体结合，伪结和共折叠，其中环路预计将发挥主导作用：盐依赖的静电环路能量可以直接合并，并包括-取决于理论建模的水平-扩散束缚的反离子，非线性静电效应和离子特异性效应的影响。小配体与RNA碱基的结合可以通过环自由能的修饰来粗略地解释。处理伪结需要在基本水平上修改迭代方程。两个或更多甚至更多的RNA链的共折叠对应于形式主义的直接修改。

We have recently extended the existing theoretical framework for predicting RNA secondary structures so that arbitrary loop free energies for multiloops of any topology are taken into account explicitly in polynomial computational time (T. R. Einert et al., PRL 101, 048103 (2008)). Melting curves and temperatures agree with experimental results. In addition, contact-pair probabilities and force-extension curves are readily obtained within our formalism. All results are surprisingly sensitive to details of the thermodynamic loop modeling even for relatively short RNA sequences. In this proposal we plan to extend the formalism even further and apply it to a few biologically relevant situations such as salt-effects, ligand binding, pseudo-knots and co-folding, where loops are expected to play a dominant role: The salt-dependent electrostatic loop energy can be directly incoporated and includes –depending on the level of theoretical modeling- the influence of diffusely bound counterions, non-linear electrostatic effects, and ion-specific effects. the binding of small ligands to the RNA bases can on a coarse-grained way be accounted for by a modification of the loop free energy. Treating pseudo-knots requires modifications of the iteration equations on a basic level. The co-folding of two or more even more RNA chains corresponds to a straightforward modification of the formalism.