EFFECTS OF COMPUTATIONAL VARIATIONS FOR DETERMINING BINDING-ENERGIES OF DIASTEREOMERIC COMPLEXES WHEN USING MM2

Variations of a procedure have been examined for minimization of the energies, calculated using MM2, of two docked molecules. After doing the intramolecular minimization of the individual molecules, randomized orientations of the rigid molecules were brought together to form complexes and the nonbonded energies of interaction were then minimized. Next, pairs having energies within 4.0 kcal/mol of the most stable pair were minimized further by atom‐by‐atom relaxation of the complex. Only two repetitions of the last two steps were found to give values within 0.001 kcal/mol in more than 90% of the cases. Compared to two other variations of the procedure, this method appeared to avoid erroneous (local, not global) minima. Finally, this overall procedure was tested against chromatographic data in the literature. Using only the most stable comformer of each species, the results appeared to be in qualitative agreement with fractionation data for enantiomeric aminoethanes on a chiral packing very similar to the one modeled here. Copyright © 1990 John Wiley & Sons, Inc.