Simulative Analysis of a Truncated Octahedral DNA Nanocage Family Indicates the Single-Stranded Thymidine Linkers as the Major Player for the Conformational Variability

Three nanocages composed of 12 DNA double helices, linked by single strand thymidine linkers made by 3, 5, and 7 nucleotides, have been characterized through classical molecular dynamics simulation to evaluate in silico the specific structural and conformational features generated by the use of a thymidine bridge of different length. The three simulated nanocages are stable, and their dynamics is characterized by a slight rotational motion of the double helices, induced by the conformational variations of the thymidine linkers. Despite this rotation the helices maintain a B-DNA structure as indicated by the values of their geometrical parameters. The thymidine strands are the elements having the largest displacement from the initial 3D model and give a significant contribution to the organization of the scaffold geometry throughout definite arrangements of base stacking and hydrogen bonds between the bases. Comparative analysis indicates that the linker length modulates the interactions occurring between the thymidines conferring a conformational variability larger in the 5T and 7T than in the 3T cage.