Graphical representation of the developed pipeline: An initial interaction is extended until the full duplex, a predefined target interaction, is reached or an extension of the interaction side is no longer possible due to steric and kinetic effects. (s1) Starting from a sequence and the corresponding secondary structure, 3D models are sampled using Ernwin and subsequently clustered (s2), yielding one representative per cluster. (s3) Each of these cluster representatives is relaxed in nrun-independent SimRNA simulations. (s4) Each simulation is analyzed and a best structure is selected. Each of these ncluster × nrun structures forms the start point for a stepwise expansion. In the first step, (e1) nsim parallel, constrained SimRNA runs are performed. (e2) From the pooled structures the start structure for the next extension step is elected based on hierarchic 2D and 3D criteria. At the checkpoint (e3), we test whether the interaction region could indeed be expanded and terminate unsuccessful runs.
