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 energy conformers were found and 12 of these were also subjected to ab initio energy minimization using the 3–21G* and 6–31G* basis sets with the Spartan 5.0 package. There was reasonable agreement between the MM3-92 and ab initio results in that almost all of the conformers found by the former were also stable low energy conformers with the latter. The structure of breflate, an ester analog of brefeldin, was also determined by X-ray crystallography. There was very good agreement between experimental structures for the compound and the lowest energy conformer determined by the ab initio methods. 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 © 1999 John Wiley & Sons, Ltd.