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C3' Stereocentre of Furanose Determines the Helicity of Double-Stranded Nucleic Acids: Towards Etiology of Nucleic Acids

Kumar, A.; Tagad, A.; Patwari, G. N.

2020-08-16 biophysics
10.1101/2020.08.15.252643 bioRxiv
Show 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.

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