Comparative Study of the Bending Free Energies of C- and G-Based DNA: A-, B-, and Z-DNA and Associated Mismatched Trinucleotide Repeats.

DNA's structural flexibility plays a crucial role in various biological functions such as gene replication, repair, and regulation as well as DNA-protein recognition. We investigate the bending free energy of short DNA helices, including d(5'-(CG)C-3') in A-, B-, and Z-forms, and C- and G-rich trinucleotide repeat helices, using orientation quaternions with enhanced sampling methods. The orientation quaternion technique provides an effective method to induce rotational transformations or to restrain the orientation of certain domains of biomolecular systems. This methodology was implemented in the AMBER simulation package and used to induce DNA bending in two separate ways: free bending and directional bending. We found that the bending free energy varies quadratically for moderate bending and then becomes almost linear for larger bending angles. The left-handed Z-DNA helix was found to exhibit the highest rigidity among the canonical DNA forms studied. The mechanisms associated with bending were also investigated with evidence for type I and type II kinks depending on the sequence and the helical form considered. The duplexes exhibit high flexibility in the presence of CC and GG mismatches, particularly CGG and GGC trinucleotide repeats in the Z-form, which have the lowest bending free energies. These calculations provide new insight into the mechanics of the global conformational flexibility of DNA molecules by quantifying the energetic cost and preferred directions of bending.