Stochastic conformational search of brefeldin A and experimental structures

The macrocyclic lactone brefeldin A was used as a test molecule for the MM3 -92 Stochastic Search conformational searching algorithm. A number of low e nergy conformers were found and I:! of these were also subjected to ab init io energy minimization using the 3-21G* and 6-31G* basis sets with the Spar tan 5.0 package. There was reasonable agreement between the MM3-92 and ab i nitio results in that almost all of the conformers found bu the former were also stable low energy conformers with the latter. The structure of brefla te, an ester analog of brefeldin. was also determined by X-ray crystallogra phy. There was very good agreement between experimental structures for the compound and the lowest energy conformer determined by the ab initio method s. This was also among the lowest conformers found by MM3-92. Despite some imperfections in the MM3-92 force field, the Stochastic Search method was a powerful method for determining molecular conformation. Copyright (C) 1999 John Wiley & Sons, Ltd.