Effect of pressure on the kinetics of bulge bases in small RNAs

Using molecular dynamics simulations, we study the effect of pressure on the binding propensity of small RNAs by calculating the free energy barrier corresponding to the looped out conformations of unmatched base, which presumably acts as the binding sites for ligands. We find that the free energy associated with base looping out increases monotonically as the pressure is increased. Furthermore, we calculate the mean first passage time of conformational looping out of the base bulge using the diffusion of reaction coordinate associated with the base flipping on the underlying free energy surface. We find that the mean first passage time associated with bulge looping out increases slowly upon increasing pressures P upto 2 kbar but changes dramatically for P > 2 kbar. Finally, we discuss our results in the light of the role of hydration shell of water around RNA.