Role of Sugar Stereochemistry on Structural and Free Energy Landscape of Double-Stranded Nucleic Acids

ABSTRACT The conformational landscape of 29-mer long four stereo variants of furanosal nucleic acids and their C2’ deoxy counterparts were explored using molecular dynamics and well-tempered metadynamics simulations. The ribose containing double-stranded nucleic acids exhibit helical structure, however inversion of C3’ and/or C2’ stereocentre of ribose results in structural modification. The free energy surfaces relative to the average twist angle and end-to-end distances suggests that the configuration at the C3’ position plays a pivotal role in determining the helicity. The C3’ stereocentre acts as toggle-switch for helix to non-helical structures in double-stranded nucleic acids. Thus, the ribose containing double-stranded nucleic acids result in well-organized helical structures, while those containing xylose and lyxose show a variety of structures, which include (circular) ladder configurations. Based on the present set of results, it can be inferred that ribose containing double-stranded nucleic acids form well-defined helical structures in contrast to their C2’ and C3’ epimers.