Can Nucleobase Pairs Offer a Possibility of a Direct 3D Self-assembly?

Andrey N. Glushenkov, Dmytro M. Hovorun

The nucleobase pairs are characterized by their conformational diversity in the wild. Yet a modern nanobiotechnology utilizes their planar conformations only, developing what can be called a "planar approach". It is well established that the most energetically favorable conformations of the complementary nucleobase pairs are planar and correspond to the classical Watson-Crick nucleobase pairs. The point of interest lies in a study of a conformational capacity of the nucleobase pairs to expand the diversity of a spatial configuration and to produce the complex 3D objects from the non-planar conformations. If such a goal could be achieved, then that could definitely open the perspectives for a novel "stereo approach". For the first time, basing on the first principles, we reveal an ability of the heteroassociates of the m(1)Cyt · m(1)Thy to form up to ten observable molecular complexes under standard conditions. The first three of them have population of ~90 % at standard conditions and are highly non-planar. The most energetically favorable structure has a T-shape, while the next two have an L-shape. At the same time, we show the lack of any experimental data covering a self-assembly of the m(1)Cyt · m(1)Thy base pairs. We present a theoretical evidence of the fact that the conformational capacity of the nucleobase pairs is much richer from the perspective of their self-assembly than it is considered in the modern nanobiotechnology. The capability of a modified cytosine and a modified thymine to create significantly non-planar structures opens a way for the innovative "stereo approach" to construction of the nanobiotechnological devices. We believe that a modern nanobiotechnological basis can and should be extended with the new nucleic base pairs with innate ability for non-planar structures. We would like to especially emphasize a prognostic role of our algorithm in obtaining the new results.