Ab initio study of preferential interactions between aromatic side chains

Abstract

The study of the tryptophan–histidine adducts, derived from the crystal structures available in the Brookhaven Protein Data Bank (PDB), using as model systems indole and (δ) 5-methylimidazole [G. Alagona, C. Ghio, S. Monti, J. Phys. Chem. A, 102, 6152 (1998)], has been extended for three of them (1esaB, 1s01, and 1lla, named after the PDB file to which they belong) to also include ε and protonated 5-methylimidazole at the Hartree–Fock (HF) and the second-order Møller–Plesset (MP2) levels, employing the 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 energy, the counterpoise correction to the basis set superposition error was introduced 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 path. The position (either δ or ε) of the proton on 5-methylimidazole does not affect much the results when the aromatic rings are almost parallel or in a T-shaped imidazole-across arrangement: the MP2 energy gap between the two adducts (favoring 1s01ε and 1llaε) is about 1.5 and 0.9 kcal/mol, respectively, and becomes 1.2 and 0.7 kcal/mol when counterpoise (CP) corrected. On the contrary there is a sensitive stabilization of the adduct when the imidazole H points toward the indole ring π density (1esaBε is repulsive at the HF level, while 1esaBδ is favorable by 3.7 kcal/mol at the HF level and by 5.5 kcal/mol at the MP2 level, either CP corrected or not). The adducts involving 5-methylimidazolium are much more stable than those with 5-methylimidazole, due to the electrostatic effect 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 preferential stabilization produced by the protein partial charges are reported. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 73: 175–186, 1999