We propose an importance sampling technique for the conformational analysis of flexible molecules that bridges the gap between currently used uniform random search and random walk methods, and compare performances of these methods in their application to selected open-chain and closed-ring hydrocarbons. It is suggested that, if no information on conformational properties of a molecule is available, the optimum strategy of its conformational analysis should include a uniform random search followed by an importance sampling biased as prescribed by the uniform search and concluded by a random-walk or genetic algorithm routine to rectify the properties of the most important parts of the conformational space.

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Slit1/2 and Robo1/2 knockout mice when compared to heterozygous controls. Mutant SN-VTA axons spread out in the diencephalon to form a wider tract. Phenotypes included invasion of the ventral midline, consistent with Slit repulsion. However, individual axons also wandered in aberrant dorsal trajectories, which suggests an unexpected role for Slits. Based on these and previous results we suggest that Slit/Robo signaling is necessary for correct dorsal/ ventral positioning and precise pathfinding of dopaminergic longitudinal axons, as well as serving a repellant function. These results may provide important insights into treatment of degeneration of SN-VTA dopminergic fibers in Parkinson's and Alzheimer's disease.