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Why does β-cyclodextrin prefer to bind nucleotides with an adenine base rather than other 2′-deoxyribonucleoside 5′-monophosphates?

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Abstract

β-Cyclodextrin (β-CD), which resides in the α-hemolysin (αHL) protein pore, can act as a molecular adapter in single-molecule exonuclease DNA sequencing approaches, where the different nucleotide binding behavior of β-CD is crucial for base discrimination. In the present contribution, the inclusion modes of β-CD towards four 2′-deoxyribonucleoside 5′-monophosphates (dNMPs) were investigated using quantum mechanics (QM) calculations. The calculated binding energy suggests that the binding affinity of dAMP to β-CD are highest among all the dNMPs in solution, in agreement with experimental results. Geometry analysis shows that β-CD in the dAMP complex undergoes a small conformational change, and weak interaction analysis indicates that there are small steric repulsion regions in β-CD. These results suggest that β-CD has lower geometric deformation energy in complexation with dAMP. Furthermore, topological analysis and weak interaction analysis suggest that the number and strength of intermolecular hydrogen bonds and van der Waals interactions are critical to dAMP binding, and they both make favorable contributions to the lower interaction energy. This work reveals the reason why β-CD prefers to bind dAMP rather than other dNMPs, while opening exciting perspectives for the design of novel β-CD-based molecular adapters in the single-molecule exonuclease method of sequencing DNA.

The binding affinity of β-cyclodextrin towards four 2′-deoxyribonucleoside 5′-monophosphates was investigated using quantum mechanics calculations

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Acknowledgments

This study was supported by the Natural Sciences Foundation of Shandong Province, China (No. ZR2013BL014, No. ZR2016BQ33 and No. ZR2012CL01), the Science and Technology Development Project of Taian City, China (No. 2016GX1023), the Taishan Medical University (No. 2015GCC20) and the Taishan University (No. Y-01-2014013).

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Authors and Affiliations

  1. College of Radiation, Taishan Medical University, Taian, 271016, People’s Republic of China

    Dongsheng Zhang

  2. College of Chemistry and Chemical Engineering, Taishan University, Taian, 271021, People’s Republic of China

    Jingjing Liu

  3. College of Chemistry and Pharmaceutical Engineering, Taishan Medical University, Taian, 271016, People’s Republic of China

    Teng Wang & Liping Sun

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  1. Dongsheng Zhang
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  2. Jingjing Liu
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Correspondence to Teng Wang.

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Zhang, D., Liu, J., Wang, T. et al. Why does β-cyclodextrin prefer to bind nucleotides with an adenine base rather than other 2′-deoxyribonucleoside 5′-monophosphates?. J Mol Model 23, 149 (2017). https://doi.org/10.1007/s00894-017-3325-9

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