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 crown ether 18-crown-6 generated by a new approach are presented in this communication. Initial geometries were obtained by local perturbations, which were then minimized using the AMBER force field. The thoroughness of the conformational sampling was ensured by a gradual expansion of the search space from the low to the higher energy regions. The power of this approach in sampling the conformational space is highlighted by the ability to generate the experimentally observed conformations and all the populated conformations visited in a detailed molecular dynamics simulation reported in literature. The new program offers a useful technique for probing the complex conformational behavior of cyclic molecules, which are active at receptors and other biologically active accepters.