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

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journal contribution
posted on 10.10.2000, 00:00 by Marialore Sulpizi, Paolo Carloni
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. Science 1998, 282, 1669−1675) and (ii) the Tyr6-Thr13 adduct in μ-gluthatione transferase (μ-GST) (Xiao, G., et al. Biochemistry 1996, 35, 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 pKa is compared with that of other interacting groups at the active site.