Theoretical investigation of histidine-tryptophan preferential interactions

Several histidine-tryptophan complexes (either stacked or T-shaped), derive d from the crystal structures available in the Brookhaven Protein Data Bank , have been examined with molecular mechanics (MM), using the Tripes force held with Gasteiger-Huckel charges, whose trend was found to be analogous t o the AMBER or CHARMM ones. The MM results were compared to the ab initio M P2 results, with and without counterpoise (CP) correction, previously obtai ned using extended basis sets on 5-methylimidazole and indole as model syst ems. MM seems to underestimate the interaction energy between the two monom ers when compared to the uncorrected MP2 results, while the agreement is mu ch 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 en ergy on the ring rotation at a variable distance and ring centroid displace ment for these systems, while keeping the rings in parallel planes. An anal ogous study was carried out for a T-shaped adduct.