Reciprocal space refinement, of electron density

In using cross-validation it is essential to avoid, or at least minimize, bias to the free R factor itself. In the era of emerging automated procedures for modelling and refinement a frequent mistake is to set aside a fraction of reflections for minimization of the residual in reciprocal space and, at the same time, to use all data for computation of electron density and model rebuilding. Since local adjustment of the model in real space is equivalent to global phase adjustment in reciprocal space, the free reflection set becomes biased towards the current model and loses its validation credibility. 

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