Cation-π versus OH-π Interactions in Proteins:  A Density Functional Study

Structure and bonding of a cation-π complex and an OH-π adduct are investigated using density functional theory with gradient-corrections for the exchange-correlation functional. Our calculations are carried out for two specific model complexes representing (i) the thymine/Arg 72 adduct in the ternary complex of HIV-1 reverse transcriptase (RT) with a DNA template primer and a deoxynucleoside triphosphate (Huang, H., et al<i>.</i> <i>Science</i> <b>1998</b>, <i>282</i>, 1669−1675) and (ii) the Tyr6-Thr13 adduct in μ-gluthatione transferase (μ-GST) (Xiao, G., et al. <i>Biochemistry</i> <b>1996</b>, <i>35</i>, 4753−4765). We find that electrostatic interactions play an important role and provide similar stabilization energies to the two π complexes. In HIV-1 RT, the π electronic density of thymine is essentially uneffected by the presence of the arginine guanidium group; on the contrary, tyrosine is significantly polarized by the interaction with the hydroxyl group and other groups present in the μ-GST enzyme. The influence of Thr13 induced-polarization on Tyr6 p<i>K</i>_a is compared with that of other interacting groups at the active site.