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

TL;DR

This study uses molecular dynamics simulations to investigate how increasing pressure influences the free energy and kinetics of bulge base looping in small RNAs, revealing significant changes above 2 kbar.

Contribution

It provides new insights into pressure effects on RNA conformational dynamics and the role of hydration shells, which were not previously characterized.

Findings

Free energy of base looping out increases with pressure.

Mean first passage time rises slowly up to 2 kbar, then sharply.

Hydration shell effects are discussed in relation to pressure-induced changes.

Abstract

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.