Thermodynamic and structural insights into RNA stretching: size, composition, and secondary structure effects

A Kroyan and SK Schnell, MOLECULAR PHYSICS, 123 (2025).

DOI: 10.1080/00268976.2025.2477212

Small single-stranded non-coding ribonucleic acids (RNAs) perform several critical functions within living cells. However, the thermodynamics of nanoscale RNA strains remain poorly understood. In this work, we studied the non-equilibrium and size-dependent thermodynamics of stretching and relaxation for various RNA strain lengths (N = 5, 10, and 50), compositions (poly-adenosine, guanosine, cytidine, and uridine), and secondary structure complexities (hairpin loops: 1ZIG and 2KOC) using molecular dynamics simulations. We calculate the Gibbs and Helmholtz energies during stretching, as well as the degree of base stacking for each molecule as a function of elongation. Trends in thermo-mechanical properties dependent on RNA size, type, and structural complexity are highlighted. We observe fluctuations in force during length-controlled (isometric) simulations and fluctuations in length during force-controlled (isotensional) simulations. Our findings indicate that the role of base stacking on chain stability during stretching is influenced by RNA size, nucleobase type, and chain complexity (single-stranded vs. hairpin). Lastly, we investigate the energetic cost of repeated stretching and relaxation in both water and vacuum environments.

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