Theoretical investigation of histidine-tryptophan preferential interactions

Several histidine-tryptophan complexes (either stacked or T-shaped), derived from the crystal structures available in the Brookhaven Protein Data Bank, have been examined with molecular mechanics (MM), using the Tripes force field with Gasteiger-Huckel charges, whose trend was found to be analogous to the AMBER or CHARMM ones. The MM results were compared to the ab initio MP2 results, with and without counterpoise (CP) correction, previously obtained using extended basis sets on 5-methylimidazole and indole as model systems. MM seems to underestimate the interaction energy between the two monomers when compared to the uncorrected MP2 results, while the agreement is much better after including the CP correction at the MP2 level in all cases. MM was thus used to qualitatively analyse the dependence of the stacking energy on the ring rotation at a variable distance and ring centroid displacement for these systems, while keeping the rings in parallel planes. An analogous study was carried out for a T-shaped adduct.