Modeling RNA secondary structures with explicit loop free energies

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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.