Cation-pi versus OH-pi interactions in proteins: A density functional study

Structure and bonding of a cation-pi complex and an OH-pi adduct are invest igated using density functional theory with gradient-corrections for the ex change-correlation functional. Our calculations are carried out for two spe cific model complexes representing (i) the thymine/Arg 72 adduct in the. te rnary complex of HIV-I reverse transcriptase (RT) with a DNA template prime r and a deoxynucleoside triphosphate (Huang, H., et al. Science 1998, 282, 1669-1675) and (ii) the Tyr6-Thr13 adduct in mu -gluthatione transferase (m u -GST) (Xiao, G., et al. Biochemistry 1996, 35, 4753-4765). We find that e lectrostatic interactions play an important role and provide similar stabil ization energies to the two pi complexes. In HIV-1 RT, the pi electronic de nsity of thymine is essentially uneffected by the presence of the arginine guanidium group; on the contrary, tyrosine is significantly polarized by th e interaction with the hydroxyl group and other groups present in the mu -G ST enzyme. The influence of Thr13 induced-polarization on Tyr6 pK(a) is com pared with that of other interacting groups at the active site.