Conformational deviation of Thrombin binding G-quadruplex aptamer (TBA) in presence of divalent cation Sr2+: A classical molecular dynamics simulation study

Thrombin binding TBA-G-quadruplex aptamer (TBA) plays a major role in blood coagulation cascade. The 15-mer TBA sequence tends to form four-stranded TBA-G-quadruplex structure. In this research work, a series of explicit solvent classical MD simulations of the TBA is carried out using different salt (SrCl2) concentrations (0, 50, 100 and 200 mM). Here we have also testified the effect of salt concentration of divalent cation Sr2+ on the conformational change of quadruplex DNA. The structural deviations, fluctuations, torsional angles and the affinity of the ion are explored at different salt concentrations. It is found that the conformation of TBA-G-quadruplex at 0 mM and 50 mM salt concentrations, is very much different than the other salt concentrations (100 mM and 200 mM). Also observed are as follows: (i) no exchange of Sr2+ ion between inside and outside of the channel, (ii) an enhancement in the Sr2+ ion density around the phosphate region of the loop residues as salt concentration increases and (iii) the stacking of T3 and T4 residues of loop-1 that appears up to 50 mM concentration, vanishes as the salt concentration is increased further.