Design and characterization of symmetric nucleic acids via molecular dynamics simulations

Asymmetry (5 '-> 3 ') associated with each strand of the deoxyribonucleic acid (DNA) is inherent in the sugar- phosphate backbone connectivity and is essential for replication and transcription. We note that this asymmetry is due to one single chemical bond (C-3 ' to C-2 ') in each nucleotide unit, and the absence of this bond results in directionally symmetric nucleic acids. We also discovered that creation of an extra chemical bond (C-5 ' to C-2 ') can lead to a symmetric backbone. Keeping their potential synthetic and therapeutic interest in mind, we designed a few novel symmetric nucleic acids. We investigated their conformational stability and flexibility via detailed all atom explicit solvent 100-ns long molecular dynamics simulations and compared the resulting structures with that of regular B-DNA. Quite interestingly, some of the symmetric nucleic acids retain the overall double helical structure indicating their potential for integration in physiological DNA without causing major structural perturbations.