2.1 Conformational search and identification of most stable conformation for each modification:
The conformational search was done using an in-house developed TANGO tool42. The TANGO tool performs well on parallel HPC clusters with respect to scalability that reduces the time taken for calculations. The information about non-cyclic torsion angles of molecules was provided to TANGO along with the mol2 file and torsion rotation value of our choice and necessary keywords. For the modifications DC, DCS, RC, RCS, LCC, LCS, five torsion angles were identified for conformation generation. For the modifications CME & CMS, eight torsion angles were identified. For A1, five torsion angles, and for A2, A3, A4, A5 six torsion angles were identified for conformation generation. TANGO generates all the possible conformations based on the torsion rotation value given and the number of torsion angles selected for that molecule. The rotational angle was given as 30º, so that single torsion rotation can generate 12 conformers. The conformers generated for any modification will increase exponentially with an increase in the number of torsion angles. For example, DC modification is having 5 torsion angles and the angle rotation is 30º, so it generates 125 (248832) conformations. Once conformation generation is over, it calculates the MOPAC44 based energies for all the conformations based on semi-empirical methods like PM6. All conformations were sorted based on electronic energy. All the conformations were segregated based on their energy vs RMSD of the conformation compared to the lowest energy conformation. The most stable and alternate stable conformational ensembles were plotted. The sugar puckering calculations have also been carried out for the most stable conformations of each modification. The same multidimensional conformational search was carried out for all the modifications listed in Table 1 and the most stable conformations were identified for each modification and selected for further quantum calculations.