To limit computational cost whilst retaining much accuracy, Soler-Polo et al. A limitation in each of the studies above is that calculations were performed on the DNA structure in in equilibrium, where the strands are not undergoing separation as they would during replication. However, as proposed by Florian and Leszczynski, 7 the tautomeric state must be stable enough to survive the DNA cleavage within the mitosis scheme, hence, the separation of DNA strands must be considered in order to validate proton transfer between bases as a genetic mutation mechanism.