For 5 first docking conformation, we conducted refinement that allowed us to calculate energetic characteristics of the obtained complexes and rank them to pick the most stable conformation for the umbrella sampling study. For the best conformation we computed 100 ns of molecular dynamics, that showed5 the very dynamic nature of the multi-loops connecting aptamer stems. We calculated MM/PB(GB)SA energy along the trajectory, that showed continued decline of association energy that showed progressive dissociation of the insulin from the aptamer2.