Landscape of π–π and sugar–π contacts in DNA–protein interactions

Abstract

There were 1765 contacts identified between DNA nucleobases or deoxyribose and cyclic (W, H, F, Y) or acyclic (R, E, D) amino acids in 672 X-ray structures of DNA–protein complexes. In this first study to compare π-interactions between the cyclic and acyclic amino acids, visual inspection was used to categorize amino acid interactions as nucleobase π–π (according to biological edge) or deoxyribose sugar–π (according to sugar edge). Overall, 54% of contacts are nucleobase π–π interactions, which involve all amino acids, but are more common for Y, F, and R, and involve all DNA nucleobases with similar frequencies. Among binding arrangements, cyclic amino acids prefer more planar (stacked) π-systems than the acyclic counterparts. Although sugar–π interactions were only previously identified with the cyclic amino acids and were found to be less common (38%) than nucleobase–cyclic amino acid contacts, sugar–π interactions are more common than nucleobase π–π contacts for the acyclic series (61% of contacts). Similar to DNA–protein π–π interactions, sugar–π contacts most frequently involve Y and R, although all amino acids adopt many binding orientations relative to deoxyribose. These DNA–protein π-interactions stabilize biological systems, by up to approximately −40 kJ mol⁻¹ for neutral nucleobase or sugar–amino acid interactions, but up to approximately −95 kJ mol⁻¹ for positively or negatively charged contacts. The high frequency and strength, despite variation in structure and composition, of these π-interactions point to an important function in biological systems.

Keywords:

• DNA–protein interactions
• X-ray crystal structure analysis
• π-interactions
• DFT calculations
• π-containing amino acids

Acknowledgments

Computational resources from the Upscale and Robust Abacus for Chemistry in Lethbridge (URACIL) and those provided by Westgrid and Compute/Calcul Canada are greatly appreciated. C. Stinnissen and Dr J. Kellie are thanked for their contributions in preliminary project planning.

Additional information

Funding

This work was supported by Natural Sciences and Engineering Research Council of Canada [grant number 249598-07]; Canada Research Chain Program [grant number 950-228175]; Canadian Foundation of Innovation [grant number 22770]; and Natural Sciences and Engineering Research Council of Canada Alexander Graham Bell Canada Graduate Scholarship-Masters and the University of Lethbridge to K.A.W.