Hotter isn't faster for a melting RNA hairpin

TL;DR

This study reveals that RNA hairpin denaturation time does not always decrease with temperature, showing a non-monotonous relationship with an optimal temperature above the melting point, due to two distinct denaturation pathways.

Contribution

It uncovers the existence of two different denaturation pathways and their impact on RNA hairpin melting dynamics, challenging traditional Arrhenius law expectations.

Findings

Denaturation time is non-monotonous with temperature for longer RNA molecules.

Two pathways, unidirectional and bidirectional, dominate at different temperature regimes.

A crossover temperature separates the two regimes, scaling with molecule length.

Abstract

We investigate the denaturation dynamics of nucleic acids through extensive molecular dynamics simulations of a coarse-grained RNA hairpin model. In apparent contradiction with Arrhenius' law, our findings reveal that the denaturation time of RNA hairpins is a non-monotonous function of temperature for molecules longer than few persistence lengths, with an optimal temperature above the melting point, $T_m$, 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 $T_m$, 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 \textit{vs.} length, $L$, and are separated by a crossover temperature $T_\times$, with $(T_\times-T_m) \sim L^{-1}$. The results highlight the significant role of the helical structure in the out-of-equilibrium dynamics of RNA/DNA denaturation and unveil multiple surprises in a decades-old problem.