Contribution of cation-pi interactions to the stability of protein-DNA complexes

Cation-pi interactions between an aromatic ring and a positive charge locat ed above it have proven to be important in protein structures and biomolecu le associations. Here, the role of these interactions at the interface of p rotein-DNA complexes is investigated, by means of nb initio quantum mechani cs energy calculations and X-ray structure analyses. Ab initio energy calcu lations indicate that Na ions and DNA bases can form stable cation-pi compl exes, whose binding strength strongly depends on the type of base, on the p osition of the Na ion, and whether the base is isolated or included in a do uble-stranded B-DNA. A survey of protein-DNA complex structures using appro priate geometrical criteria revealed cation-pi interactions in 71% of the c omplexes. More than half of the cation-pi pairs involve arginine residues, about one-third asparagine or glutamine residues that only carry a partial charge, and one-seventh lysine residues. The most frequently observed pair, which is also the most stable as monitored by ab initio energy calculation s, is arginine-guanine. Arginine-adenine interactions are also favorable in general, although to a lesser extent, whereas those with thymine and cytos ine are not. Our calculations show that the major contribution to cation-pi interactions with DNA bases is of electrostatic nature. These interactions often occur concomitantly with hydrogen bonds with adjacent bases; their s trength is estimated to be from three to four times lower than that of hydr ogen bonds. Finally, the role of cation-pi interactions in the stability an d specificity of protein-DNA complexes is discussed. (C) 2000 Academic Pres s.