NEW TECHNIQUE FOR CONFORMATIONAL SAMPLING OF CYCLIC MOLECULES USING THE AMBER FORCE-FIELD - APPLICATION TO 18-CROWN-6

The results of an exhaustive search of low-energy conformers of the cr own ether 18-crown-6 generated by a new approach are presented in this communication. Initial geometries were obtained by local perturbation s, which were then minimized using the AMBER force field. The thorough ness of the conformational sampling was ensured by a gradual expansion of the search space from the low to the higher energy regions. The po wer of this approach in sampling the conformational space is highlight ed by the ability to generate the experimentally observed conformation s and all the populated conformations visited in a detailed molecular dynamics simulation reported in literature. The new program offers a u seful technique for probing the complex conformational behavior of cyc lic molecules, which are active at receptors and other biologically ac tive accepters.