Directed tweak technique

An important extension to rigid-body fitting is the so-called directed tweak technique [105]. Directed tweak allows for an RMS fit, simultaneously considering the molecular flexibility. By the use of local coordinates for the handling of rotatable bonds, it is possible to formulate analytical derivatives of the objective function. With a gradient-based local optimizer flexible RMS fits are obtained extremely fast. However, no torsional preferences may be introduced. Therefore, directed tweak may result in energetically unfavorable conformations. 

Hurst, T. Flexible 3D searching the directed tweak technique. /. Chem. Inf. Comput. Sci. 1994, 34, 190-196. 

Hurst, T. 1994. Flexible 3D searching The Directed Tweak technique. J Chem Inf Comput Sci 34 190-6. 

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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