Abstract: MATH/CHEM/COMP 2002, Dubrovnik, June 24-29, 2002

THE OVERLAPPING SPHERES METHOD FOR FINDING LOW-ENERGY CONFORMATIONS: COMPARISON OF TWO APPROACHES IN THE CASE OF COPPER(II) bis-COMPLEXES WITH 1-[N-(tert-BUTOXYCARBONYL)AMINO]-2-HYDROXYMETHYLCYCLOPROPANE-1-CARBOXYLIC ACIDS

Lora zuza and Nenad Raos

Institute for Medical Research and Occupational Health, 10001 Zagreb, P. O. B. 291, Croatia

The model of overlapping spheres (OS) for finding the low-energy conformations¹ – which is based on the minimization of the van der Waals excluded volume inside the sphere with radius R_v, centered at the geometrical center of a molecular fragment – was applied on three stereoisomers, (N-S,1S,2R)(N-S,1S,2R), (N-R,1S,2R)(N-S,1R,2S), and (N-R,1S,2S)(N-S,1R,2R), of copper(II) bis-chelates with 1-[N-(tert-butoxycarbonyl)amino]-2-hydroxymethylcyclopropane-1-carboxylic acid.

A new searching approach (stream method) was introduced and compared to the previously used one (sieve method). Both methods try to find the low-energy conformations through the combination of different values of central sphere radius (R_v = 0.3, 0.4, 0.5, 0.6 nm) and different molecular fragmentation. In the sieve method for the next minimization run the currently lowest-energy conformation is always chosen. In the stream method the minimization protocol is followed irrespectively of the obtained conformation energy in the previous run. For the initial, “seed”, conformation one conformer of each of the three stereoisomeric complexes was chosen.

 By using the stream method 87 conformations were obtained in 171 minimization runs, and the sieve method yielded 95 conformations after 252 runs. It gives the efficiency of 51% and 38% for the stream and the sieve method, respectively. The lowest-energy conformer was obtained usually faster by using the stream method, although in some cases the conformation with the lowest energy was obtained by the sieve method (3 out of 9 pairs). However, the maximal difference between those 3 pairs of conformations was 5.38 kJ mol^-1. Average decrease in conformational energy (from the energy of initial, “seed”, conformation to the lowest energy conformation of each stereoisomeric complex) in both methods is similar (26.04 kJ mol^-1 and 26.67 kJ mol^-1 for the stream and the sieve method, respectively). The conformations with the energy higher than the initial one were seldom obtained by both methods (4 out of 182).

Results obtained show that the stream method is better fitted for the search of the  lowest-energy conformation and also for the generation of new conformations.

¹ N. Raos, J. Comput. Chem. 21 (2000) 1353.