(297d) Atomistic Simulations of RNA Folding in Bulk Aqueous Solutions and under Confinement

RNA is an essential molecule of life and is a promising agent to base drug and vaccine formulations. RNA is often encapsulated for pharmaceutical formulations, synthetic biology applications, and also for studying its evolution in the context of the origins of life. Encapsulation fundamentally alters thermodynamic conditions by reducing the available volume and modifying the chemistry of the surroundings. To investigate the effects of encapsulation on RNA folding, here we performed advanced sampling simulations of folding an explicitly solvated, all-atom GAGA tetraloop (10-nucleotides) encapsulated in model surfaces. We systematically modified the surface attractiveness and sizes of encapsulating sphere. We found that folded state is destabilized in the encapsulated RNA (with respect to the RNA in bulk aqueous solution) regardless of the attractiveness of the encapsulating surface or the size of encapsulation within the range we tested.