Directed tweak algorithm

Another optimization method, related to the least-squares fitting used in point-based algorithms, is the directed tweak method [31]. This is a torsional space optimizer, in which the rotatable bonds of the ligands are adjusted at search time to produce a conformation which matches the 3D query as closely as possible. As directed tweak involves the use of analytical derivatives, it is very fast and allows for an RMS fit to consider ligand flexibility. 

Alignment methods are also known to combine different optimization methods, such as a genetic algorithm and a directed tweak method [36]. 

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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