• VLD;
  • hybrid Fourier synthesis;
  • difference electron density;
  • joint probability distribution function;
  • density modification;
  • phase estimation

The VLD (vive la difference) phasing algorithm combines the model electron density with the difference electron density via reciprocal space relationships to obtain new phase values and drive them to the correct values. The process is iterative and has been applied to small and medium-size structures and to proteins. Hybrid Fourier syntheses show properties that are intermediate between those of the observed synthesis (whose peaks should correspond to the most probable atomic positions) and those of the difference synthesis (whose positive and negative peaks should correspond to missed atomic positions and to false atoms of the model, respectively). Thanks to these properties some hybrid syntheses can be used in the phase extension and refinement step, to reduce the model bias and more rapidly move to the target structure. They have been recently revisited via the method of joint probability distribution functions [Burla, Carrozzini, Cascarano, Giacovazzo & Polidori (2011). Acta. Cryst. A67, 447–455]. The results suggested that VLD could be usefully combined, for ab initio phasing, with the hybrid rather than with the difference Fourier synthesis. This paper explores the feasibility of such a combination and shows that the original VLD algorithm is only one of several variants, all with relevant phasing capacity. The study explores the role of several parameters in order to design a standard procedure with optimized phasing power.