We first focused on simulating the parent system which contains the imidazolium-bridged guanosine dinucleotide (GpAIpG) as in the original crystal structure acquired by Zhang et al. . Activated guanosine nucleotides were previously shown to offer the highest rate and fidelity in nonenzymatic primer extension reactions and here we this system as the reference point in the structural analyses. The geometry clustering analysis based on the DBSCAN algorithm found only one cluster which was populated for 86.0% of the simulation time. The structure with the lowest cumulative distance to all remaining frames within this cluster (our representative frame) is characterized by the anti conformation of both guanine nucleobases of GpAIpG and the C3 ′ -endo conformation of the corresponding sugar moieties. GpAIpG is bound to the template with Watson-Crick (WC) base pairing interactions and it is additionally stabilized by stacking with the guanine nucleobase in the 3 ′ -end of the copied strand (see Fig. )). The K-means clustering analysis revealed several cluster structure which differ by minor details, but possess the same conformational features and binding mode as the structure representing the cluster identified with the DBSCAN algorithm (see Supporting Information Fig. ). The overall population of such bound structures from the K-means procedure closely resembles the population of the main cluster from DBSCAN (94%). Overall, these results demonstrate that high rates and fidelities of nonenzymatic template copying are well reflected by stable binding of the dinucleotide intermediate through Watson-Crick base-pairing interactions and high population of the corresponding bound structures.