Structure–activity relationships of a caged thrombin binding DNA aptamer: Insight gained from molecular dynamics simulation studies

15-mer ssDNA aptamers play a vital role in the inhibition of α-thrombin in the blood clotting mechanism. It is of high importance to explore the structural factors controlling the inhibitory nature of the aptamer. Here we investigated the structure–function relationship of the anti-thrombin aptamer, as well as its ‘caged’ variant (2-(2-nitrophenyl)-propyl group (NPP)) by molecular dynamics simulations. The stability of the unmodified aptamer at different temperatures is examined in 2 ns all-atom simulations and compared to experiment. The change in structure when introducing the photo-labile caged compound is analyzed, and the regiospecificity of this modification explained on atomic level. Removal of the photo-labile group leads to the reformation of the active aptamer structure from its inactive state. The mechanism for this formation process is a concerted movement of the aptamer backbone and some highly important bases. The binding of the aptamer to thrombin with regard to the ‘caged’ group is studied in an explicit simulation with the aptamer–thrombin complex and the reason for the binding/unbinding nature of the aptamer shown.