When molecular replacement has no trivial solution: The importance of model editing in human S100Z X-ray structure solution

Molecular replacement (MR) is normally a successful technique to solve the phase problem in protein Xray crystallography. Its use is more and more common, taking advantage of the ever increasing number of structures deposited in the PDB; in MR a structure homologous to the target one is used as a template to obtain the phase values needed for computing electron density. There are however situations that may hinder MR success, such as low diffraction data quality, pseudo-translation, twinning, high order non crystallographic symmetry (NCS) within the asymmetric unit and, last but not least, the quality of the model used as the template. Solving the X-ray structure of human apo-S100Z by MR turned out to be a challenge and required trying several approaches and software tools; in an attempt to help researchers who may encounter this type of difficulties, we illustrate the attempted and failed MR approaches and speculate on the plausible reasons for which only certain approaches allowed to overcome the difficulties encountered. More importantly, we stress the crucial importance of a proper model editing for a successful protein structure solution through MR.