The polymerase enzyme hardly differentiates between thymine and difluorotoluene nucleotides with respect to the replication selectivity. X-ray structure analysis show the importance of the Watson-Crick geometry for the replication fidelity; base selection is determined by the spatial prerequisite of the substrate pocket and directed protein interactions in the minor groove (schematically shown on the right).
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Ulf Diederichsen (1998) studied this question.