We performed classical molecular dynamics simulations for 9 variants of a self-replicating RNA system using the crystal structure structure deposited by Zhang et al. [PDB:6C8K] as the initial model system. Our self-replicating RNA model system consists of a templating strand having 14 nucleotides, the copied strand of 12 nucleotides and a imidazole-bridged dinucleotide intermediate located near the 3 ′ -end of the copied strand, which interacts with the terminal nucleotides of the templating strand through Watson-Crick base pairing (see Fig. ). The 9 variants of this system include different compositions of the imidazolium-bridged dinucleotide intermediate including constituent nucleotides such as: guanosine, cytidine, uridine, adenosine, inosine and 2-thiouridine (see Fig. ). Each of these variants also contained the appropriate complementary nucleotides on the templating strand. After the equilibration runs which maintained all the Watson-Crick base pairing interactions, we performed production MD simulations with the cumulative time of 1.5 µs for each of these systems (more details can be found in the Methods section).