Main Mechanical Forces to Analyse the Chemical Interactions Shaping Backbone Torsion Angles in DNA Tertiary Structures

The genetic material in living systems is mainly stored in DNA molecules, which in turn play a dominant biological role in relation to the coding and transfer of genetic information, the biosynthesis of proteins and RNA and the packaging and regulation of DNA expression and accessibility. These features, strictly dictated by the three-dimensional structure of DNA, are governed by non-covalent chemical interactions that drive the folding process of these biological macromolecules. The Main Mechanical Forces (MMFs) approach is a recently formulated calculation method, based on the accurate prediction of structural features of biomolecules through an in-depth assessment of the interplay between specific non-covalent chemical interactions and related mechanical forces developed during the folding process. By adopting the MMFs method in the context of nucleic acids, we report here the results obtained in terms of predicting three-dimensional DNA oligomer tertiary structures. To this end, we have developed tailored nucleic acid-specific equations, enabling to predict the torsion angles (with a relevant level of agreement with experimental values) of the phosphate-sugar backbone of the three model molecules A-, B- and Z- DNA used in this study. To increase the validity of this methodology, we have conducted RMSD measurements, indicating that there is a weak but rather acceptable match between the calculated vs. predicted A-DNA structure, whereas the prediction of the BII-DNA and Z-DNA tertiary structures was fully correct.