PSEUDOSYSTEMATIC CONFORMATIONAL SEARCH - APPLICATION TO CYCLOHEPTADECANE

We describe a deterministic approach to conformational searching. The algorithm is a best-first, depth-first traversal of the conformer grap h, i.e., a graph generated by a small set of deterministic deformation operators. No deformation operator is ever applied to the same starti ng structure more than once. Thus, this algorithm avoids the source of diminishing returns, common in Monte Carlo searches, that is caused b y the rising probability that a given starting structure is subjected to the same or similar perturbations more than once. We apply this tec hnique to the task of finding all locally optimal conformations of cyc loheptadecane whose MM2 energies lie within 3 kcal/mol of its global o ptimum. This task, which is considered to be challenging for contempor ary algorithms and computer hardware, was used by Saunders et al. (J. Am. Chem. Sec. 1990, 112, 1419-1427) as a benchmark for comparing exis ting techniques in terms of their efficiency and thoroughness. The new algorithm compares favorably, by both criteria, with all of the metho ds tested by Saunders et al. Moreover, the conformer graph can be used for an analysis of the potential-energy surface that is not directly made possible by other search methods. The particular set of deformati on operators used is specialized for medium-sized ring molecules. Ways to design deformation operators for larger molecules such as proteins are suggested.