POLING - PROMOTING CONFORMATIONAL VARIATION

This article introduces several methods of assessing the extent to whi ch a collection of conformations represents or covers conformational s pace. It also describes poling: a novel technique for promoting confor mational variation that can be applied to any method of conformational analysis that locally minimizes a penalty or energy function. The fun ction being minimized is modified to force similar conformers away fro m each other. The method is independent of the origin of the initial c onformers and of the particular minimization method used. It is found that, with the modification of the penalty function, clustering of the resulting conformers is generally unnecessary because the conformers are forced to be dissimilar. The functional form of the poling functio n is presented, and the merits are discussed with reference to (1) eff icacy at promoting variation and (2) perturbation of the unmodified fu nction. Results will be presented using conformers obtained from dista nce geometry with and without poling. It will be shown that the additi on of poling eliminates much redundancy in conformer generation and im proves the coverage of the conformational space. (C) 1995 by John Wile y and Sons, Inc.