ABSTRACT
Ribose containing double-stranded nucleic acids exhibit helical structure, whereas sugar modified (xeno) nucleic acids may exhibit different structural features. The structural landscape of four stereo variants of furanosal nucleic acids and their C2′ deoxy counterparts, explored with molecular dynamics simulations, suggest that the configuration at the C3′ position plays a pivotal role in determining the helicity. The C3′ stereocentre acts as toggle-switch for the helix to ladder structural transformation by changing the nature of intra-strand interactions resulting in the optimal helices for ribose containing double-stranded nucleic acids. Interestingly, lack of chirality at the C2′ position results in better quality helices than inversion of stereochemistry relative to ribose. The etiology of furanosal-RNA over other furanoses can be hypothesized based on the helical structure, which can effectively be exploited by the biological machinery.
SIGNIFICANCE The double helix structure of furanosal RNA is governed by the configuration at the C3′ position. Furanose sugars such as xylose and lyxose where in the configuration at the C3′ position is inverted relative to the ribose do not form double helix structure, instead result in ladder-like structure. The configuration at the C3′ position acts as a toggle switch for the helix to ladder structural transition. Among four furanose sugars viz., ribose, arabinose, xylose, and lyxose, the double-stranded nucleic acids incorporating ribose form helices with best aspect ratio between major and minor grooves.
Competing Interest Statement
The authors have declared no competing interest.