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Score optimization allows the conformation and orientation of a molecule to be adjusted to improve the score. Although the calculation is expensive, it makes the conformation and orientation search more efficient because less sampling becomes necessary. Optimization is activated with the minimize_ligand parameter. The optimizer currently uses the simplex algorithm, which does not require evaluation of derivatives (Nelder et al, ComputerJournal, 1964). It does however depend on a random number generator which makes it sensitive to the initial seed provided with random_seed parameter. The amount of variance should be small, though. For detailed calculations, it is recommended that the optimization be repeated with different random number seeds to check convergence.
The initial step size of the minimizer is specified with the initial_translation, initial_rotation, and initial_torsion parameters. The length of minimization may be controlled with the maximum_iterations parameter. Users can choose to minimize the rigid anchors, minimize during flexible growth, and minimize the final conformation. The anchor minimization is always done rigidly; also, if no flexible growth is being done, this step will minimize the entire molecule. The minimization during the flexible growth is a complete (torsions + rigid) minimization. When the simplex shrinks enough so that the highest and lowest points are within the scoring tolerance or if the number of requested minimizer steps is reached, the minimizer terminates.