Random tweak

Two procedures based on random search have been reported for predicting loop conformations for use in homology modeling. Shenkin, Yarmush, Fine, Wang, and Levinthal s random tweak method is designed to address the problem that a randomly generated conformation may fail to satisfy the imposed... 

Kilvington and Leach have applied the random tweak algorithm to determine which of a series of possible acyclic linkers (determined randomly or systematically) is suitable to connect two isolated ligand fragments. The random tweak method is used to determine the amount of rotation each bond must undergo to match die ends of a flexible chain to the isolated fragments. ... 

Leach and Kilvington have used the original random tweak method to join already placed fragments with simple hydrocarbon chains. This application, which is more restricted than that described above, allows the placement and fitting of general fragments and their associated interaction sites. 

Clark et al. - also compared the GA with distance geometry, directed tweak, and random search methods on the problem of finding good phar-macaphoric matches in databases df thousands of molecules. Their final conclusion is that GA and directed tweak outperform all of the methods, and that the directed tweak may in fact be preferable to GA, as mentioned earlier in this chapter. 

ChemDBS-3D uses rule-based systematic conformational analysis (single = 3, alpha 4, double/conjugated = 2 points) or random rule-based (max. time 2 min), or flexifit (no VDW bump check) ISIS/3D and UNITY use torsional minimization (conformationally flexible searching and directed tweak, respectively. 

Methods that combine a search technique with other optimization approaches include distance geometry, random search, and genetic algorithms. A comparison of these methods with derivative-based optimization concluded that all were inferior in performance to directed tweak, with the most favorable of the three being the genetic algorithm. ... 

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