Simulating an exploration of RNA conformation space with an appropriate parallel-updating strategy

A thermodynamic ensemble of stable RNA structures should emerge in the long-time limit as a result of an expeditious exploration of conformation space. The design of a simulation of this exploration giving consistent results in the long-time limit has been hindered by two main factors: (1) the need to incorporate the kinetic or activation-energy barriers for structure conversion and (2) the possibility of competing folding pathways. In this work, we implement a parallel kinetically controlled simulation that encompasses both aspects and ultimately yields all significant contributors to the thermodynamic re specialized to the illustrative cases of a transfer RNA and a midivariant-1 Qβ RNA for which the dominant native and non-native structures have been independently established. In both cases the thermodynamic ensemble is reproduced.