We performed umbrella sampling simulation of the kissing-loop complex in the add adenine riboswitch. Notably, our calculations can reproduce the cooperativity between kissing-loop formation and ligand binding, which is a nontrivial allosteric effect. However, results are far from converged. The work is instructive, since it points out some of the possible issues that could affect enhanced sampling simulations performed using the umbrella sampling method.
The work has been just accepted for publication on BMC Bioinformatics. A preprint is available on ArXiv.