Thermodynamics and kinetics of an A-U RNA base pair under force studied by molecular dynamics simulations

Mechanical force has been widely used to study RNA folding and unfolding. Understanding how the force affects the opening and closing of a single base pair, which is a basic step for RNA folding and unfolding and a fundamental behavior in some important biological activities, is crucial to understanding the mechanism of RNA folding and unfolding under mechanical force. In this work, we investigated the opening and closing process of an RNA base pair under mechanical force with constant-force stretching molecular dynamics simulations. It was found that high mechanical force results in overstretching, and the open state is a high-energy state. The enthalpy and entropy change of the base-pair opening-closing transition were obtained and the results at low forces were in good agreement with the nearest-neighbor model. The temperature and force dependence of the opening and closing rates were also obtained. The position of the transition state for the base-pair opening-closing transition under mechanical force was determined. The free energy barrier of opening a base pair without force is the enthalpy increase, and the work done by the force from the closed state to the transition state decreases the barrier and increases the opening rate. The free energy barrier of closing the base pair without force results from the entropy loss, and the work done by the force from the open state to the transition state increases the barrier and decreases the closing rate. The transition rates are strongly dependent on the temperature and force, while the transition path times are weakly dependent on force and temperature.