Ribonucleic acid (RNA) has a major biological role by participating in various complex cellular processes. The proper understanding of these processes requires the detailed description of RNA three-dimensional (3D) structure. Development of structure probing techniques is thereby drawing significant interest of researchers from both experimental and theoretical fields. In this work we tackle the established presumption by chemical probing techniques that unpaired nucleotides are automatically considered as flexible and reactive. We introduce a novel protocol for differentiating among poorly reactive nucleotides located within different RNA motifs by combining quantum mechanical/molecular mechanical (QM/MM) calculations with enhanced sampling method (metadynamics) and compute free energy profiles of phosphate cleavage reactions for all nucleotides within specific RNA structure. The results for small motifs, e.g., tetraloops and double helices, are compared with available data from in-line probing experiments and show that our technique is able to distinguish between nucleotides based on their structural predispositions towards phosphate cleavage reaction.

QM/MM approach to the phosphate cleavage of non-reactive RNA nucleotides

251st National Meeting (2016)

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