Abstract
Due to their self-catalytic properties, small RNAs with bulge bases are hypothesized to be primordial molecules which could form elementary translation systems. Using molecular dynamics simulations, we study the binding propensity of small RNAs by calculating the free energy barrier corresponding to the looped out conformations of bulge bases, which presumably act as the binding sites for ligands in these small RNAs. We find that base flipping kinetics can proceed at atmospheric pressure but with a very small propensity. Furthermore, the free energy barrier associated with base flipping depends on the stacking with neighboring bases. Next, we studied the base flipping kinetics with pressure. 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 bulge base 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 up to atm but changes dramatically for atm. Finally, we discuss our results in the light of the role of hydration shell of water around RNA. Our results are relevant for the RNA world hypothesis.
Highlights
IntroductionApart from having the regular helical purinepyrimidine base pairs, RNA molecules are found to have many other secondary structures (motifs) such as loops, knots and bulges etc [3,4]
RNA molecules are very diverse both structurally and functionally [1,2]
In this paper we have investigated the effect of neighbor stacking and pressure on the kinetics of an Adenosine bulge base embedded between (GC)2 in 59GGGGAGG3959CCCCCC39, and embedded between (CG)2 in 59CCCCACC39-59GGGGGG39, and AA-bulge embedded between (GC)2 in 59GGGGAGG39-59CCACCCC39
Summary
Apart from having the regular helical purinepyrimidine base pairs, RNA molecules are found to have many other secondary structures (motifs) such as loops, knots and bulges etc [3,4]. The presence of such structural motifs is found to play a role in binding of different molecules to RNA [5]. The presence of a bulge may change the conformational flexibility of an RNA [6,7] and more internal surface area of RNA is available for any chemistry. It has been shown that the bulge base looping out is highly sensitive to the bulge bases and their neighbors [6,7], which makes the question of generality of any picture of base bulge looping out difficult
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
