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Combining crystallographic and quantum chemical data to understand DNA-protein π-interactions in nature

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Abstract

Noncovalent interactions are accepted to be prevalent across biochemical systems, including governing interactions between nucleic acids and proteins. The present review summarizes work done to characterize the abundance, structure and strength of DNA–protein π interactions by combining rigorous searches of experimental X-ray crystal structures of DNA–protein complexes and quantum chemical calculations. Focus is placed on interactions that occur between the π-containing amino acids (W, H, F, Y, R, E, and D) and the canonical DNA nucleobases (A, T, G, and C) or 2′-deoxyribose moiety. These studies highlight the considerable frequency of both DNA–protein π–π and sugar–π interactions in nature, which can involve any π-containing amino acid arranged in many unique binding orientations with respect to any DNA component. When combined with the significant strength predicted for the identified DNA–protein π contacts using density functional theory, these works underscore the potential impact of these interactions on critical biological functions. This conclusion is supported by a review of examples from the recent literature that have acknowledged the role of DNA–protein π interactions in binding, specificity, and catalysis.

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Acknowledgements

S.D.W thanks the Natural Sciences and Engineering Research Council of Canada (NSERC; 249598-07), Canada Research Chairs Program (950-228175), and Canada Foundation of Innovation (22770). K.A.W thanks NSERC (Vanier), Alberta Innovates - Technology Futures, and the University of Lethbridge for student scholarships. Computational resources from the New Upscale Cluster for Lethbridge to Enable Innovative Chemistry (NUCLEIC), as well as those provided by Westgrid and Compute/Calcul Canada, are greatly appreciated.

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  1. Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, AB, T1K 3M4, Canada

    Katie A. Wilson & Stacey D. Wetmore

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  1. Katie A. Wilson
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  2. Stacey D. Wetmore
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Correspondence to Stacey D. Wetmore.

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This paper is dedicated to Prof. Lou Massa on the occasion of his Festschrift: A Path through Quantum Crystallography.

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Wilson, K.A., Wetmore, S.D. Combining crystallographic and quantum chemical data to understand DNA-protein π-interactions in nature. Struct Chem 28, 1487–1500 (2017). https://doi.org/10.1007/s11224-017-0954-7

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