Hotter is not faster for a melting RNA hairpin

Abstract

We investigate the denaturation dynamics of nucleic acids through extensive molecular dynamics simulations of a coarse-grained RNA hairpin model. In apparent contradiction to Arrhenius' law, our findings reveal that the denaturation time of RNA hairpins is a nonmonotonous function of temperature for molecules longer than few persistence lengths, with an optimal temperature above the melting point, Tm, at which denaturation occurs fastest. This anomaly arises from the existence of two distinct pathways: "unidirectional"unzipping, progressing from one end to the other and favored near Tm, and "bidirectional"denaturation, where competing unzipping events initiate from both ends at higher temperatures. The two regimes manifest distinct scaling laws for the melting time vs length, L, and are separated by a crossover temperature T×, with (T×-Tm)∼L-1. The results highlight the significant role of the helical structure in the out-of-equilibrium dynamics of RNA and DNA denaturation and unveil multiple surprises in a decades-old problem.