Multiple stepwise pattern for potential of mean force in unfolding the thrombin binding aptamer in complex with Sr2+

Abstract

Using all-atom molecular dynamics simulation in conjunction with umbrella sampling, we obtained the unfolding free energy and the force extension profiles of the thrombin binding DNA aptamer (15-TBA) in complex with Sr(2+) (Protein Data Bank code: 1RDE). The resulting potential of mean force (PMF) displays a multiple stepwise pattern with distinct plateau regions. The detailed analysis of the simulation result indicated that each plateau was created by the interplay of the metal ion interacting with self-arranging guanine bases and the successive uptakes of water molecules. The current PMF simulation provides a quantitative description of the unfolding process of 15-TBA DNA driven by stretching and gives molecular insight on its detailed changes of base pair interactions in the presence of the metal cation.