Ab initio study of preferential interactions between aromatic side chains

The study of the tryptophan-histidine adducts, derived from the crystal str uctures available in the Brookhaven Protein Data Bank (PDB), using as model systems indole and (delta) 5-methylimidazole [G. Alagona, C. Ghio, S. Mont i, J. Phys. Chem. A, 102, 6152 (1998)], has been extended for three of them (1esa8, 1s01, and 1lla, named after the PDB file to which they belong) to also include epsilon and protonated 5-methylimidazole at the Hartree-Fock ( HF) and the second-order M empyt set ller-Plesset (MP2) levels, employing t he 6-31G* basis set with the d exponents reduced to 0.25, thus named 6-31G* (0.25), and the HF/6-31G* internal geometries of the isolated partners. For these arrangements having a shallow or even repulsive HF interaction energ y, the counterpoise correction to the basis set superposition error was int roduced both at the HF and MP2 levels, using the 6-31G*(0.25) basis set, to test the reliability of the results obtained along the whole approaching p ath. The position (either delta or epsilon) of the proton on 5-methylimidaz ole does not affect much the results when the aromatic rings are almost par allel or in a T-shaped imidazole-across arrangement: the MP2 energy gap bet ween the two adducts (favoring 1s01 epsilon and 1lla epsilon) is about 1.5 and 0.9 kcal/mol, respectively, and becomes 1.2 and 0.7 kcal/mol when count erpoise (CP) corrected. On the contrary there is a sensitive stabilization of the adduct when the imidazole H points toward the indole ring pi density (1esaB epsilon is repulsive at the HF level, while 1esaB delta is favorabl e by 3.7 kcal/mol at the HF level and by 5.5 kcal/mol at the MP2 level, eit her CP corrected or not). The adducts involving 5-methylimidazolium are muc h more stable than those with 5-methylimidazole, due to the electrostatic e ffect of the cation, which considerably increases the interaction energies and shortens the separations. The effect produced on the complex energy and equilibrium distance by the presence of a set of polarization function on the hydrogens with either normal or reduced exponents [6-31G** and 6-31G**( 0.25, 0.15) descriptions] was also considered. Preliminary results on the p referential stabilization produced by the protein partial charges are repor ted. (C) 1999 John Wiley & Sons, Inc. Int J Quant Chem 73: 175-186, 1999.