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.