TRAVELING ON THE POTENTIAL-ENERGY SURFACES OF CARBOHYDRATES - COMPARATIVE APPLICATION OF AN EXHAUSTIVE SYSTEMATIC CONFORMATIONAL SEARCH WITH AN HEURISTIC-SEARCH

The calculated ensembles found by a heuristic conformational search al gorithm, CICADA, for three small carbohydrates, ethyl beta-lactoside, methyl alpha-D-galactoside, and methyl beta-D-galactoside, are evaluat ed in terms of their ability to reproduce time-averaged optical rotati on and NMR data. A unique dynamic model for methyl beta-D-galactoside has been obtained by fitting experimental NOESY volumes to the theoret ical ones elaborated from the CICADA ensemble internuclear distances w ith the model-free formalism. In the case of ethyl beta-lactoside, the CICADA ensemble is compared to that of an exhaustive systematic grid- search method. The CICADA algorithm proved to be a very efficient meth od to find most of the important minima on even very complex potential energy surfaces, and the spectral quality of the CICADA ensemble was found to be of equal quality, if not superior, to that of the exhausti ve systematic grid-search method. The CICADA algorithm has several adv antages over other conformational search algorithms: (1) It has polyno mial dependence of dimensions on computer time in contrast to the grid search, which has exponential dependence, (2) the conformations found are free of artificial harmonic constraint potentials, (3) it passes all barriers amongst families of conformations on conformational hyper surface but spends almost all its time in the essential highly populat ed areas, (4) the inherent properties of the algorithm make rigorous m inimization criteria superfluous and provide good convergence behavior , and (5) as an important spin-off, it provides low-energy interconver sion pathways that can, amongst others, be used for estimating adiabat ic rotational barriers.