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Effect of N7-methylation on base pairing patterns of guanine: a DFT study

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Abstract

In this paper, we aim to determine whether the N7-methylation can influence the base pairing properties of guanine by promoting the formation of guanine enol-tautomers. The keto- to -enol-tautomerization of N7-methylguanine (N7mG) and its base pairing patterns with all the canonical DNA bases have been investigated at the M06-2X/6-311+G(d,p) level of density functional theory. The barrier free energy calculations reveal that N7-methylation does not promote the keto- to enol- tautomerization of guanine. The Watson-Crick-like enol-N7mG:T1 or enol-N7mG:T2 base pair similar to what is observed experimentally is found to be energetically more stable than the keto-N7mG:T base pairs. However, the keto-N7mG:C1 which is structurally similar to the canonical G:C base pair is the most stable base pair among all the base pairs studied here. Thus, our calculations predict that N7mG would pair preferably with cytosine during DNA replication but there is also a probability that it can cause mutation through mispairing with thymine, in agreement with experimental observations.

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Acknowledgments

The authors acknowledge the general computational facility of the Department of Physics, Assam University, Silchar.

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  1. Department of Physics, Assam University, Silchar, 788011, India

    Swarnadeep Biswas & Pradeep Kumar Shukla

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  1. Swarnadeep Biswas
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SB performed simulation, data collection and partial contribution to the first draft of the manuscript. PKS planned and supervised the research work, analysis of the results and writing of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Pradeep Kumar Shukla.

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Biswas, S., Shukla, P.K. Effect of N7-methylation on base pairing patterns of guanine: a DFT study. J Mol Model 27, 184 (2021). https://doi.org/10.1007/s00894-021-04792-3

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