measured by an R-factor defined as where F is the structure factor. A similar quality criterion is Rfree, which is calculated from a subset (~10%) of reflections that were not included in the structure refinement. Both R factors depend on the resolution of the data. As a rule of thumb, Rfree should be approximately the resolution in angstroms divided by 10; thus, a data-set with 2 Å resolution should yield a final Rfree ~ 0.2. Chemical bonding features such as stereochemistry, hydrogen bonding and distribution of bond lengths and angles are complementary measures of the model quality. Phase bias is a serious problem in such iterative model building. Omit maps are a common technique used to check for this. It may not be possible to observe every atom in the asymmetric unit. In many cases, Crystallographic disorder smears the electron density map. Weakly scattering atoms such as hydrogen are routinely invisible. It is also possible for a single atom to appear multiple times in an electron density map, e.g., if a protein sidechain has multiple (<4) allowed conformations. In still other cases, the crystallographer may detect that the covalent structure deduced for the molecule was incorrect, or changed. For example, proteins may be cleaved or undergo post-translational modifications that were not detected prior to the crystallization. Disorder A common challenge in refinement of crystal structures results from crystallographic disorder. Disorder can take many forms but in general involves the coexistence of two or more species or conformations. Failure to recognize disorder results in flawed interpretation. Pitfalls from improper modeling of disorder are illustrated by the discounted hypothesis of bond stretch isomerism. Disorder is modelled with respect to the relative population of the components, often only two, and their identity. In structures of large molecules and ions, solvent and counterions are often disordered. Applied computational data analysis The use of computational methods for the powder X-ray diffraction data analysis is now generalized. It typically compares the experimental data to the simulated diffractogram of a model structure, taking into account the instrumental parameters, and refines the structural or microstructural parameters of the model using least squares based minimization algorithm. Most available tools allowing phase identification and structural refinement are based on the Rietveld method, some of them being open and free software such as FullProf Suite, Jana2006, MAUD, Rietan, GSAS, etc. while others are available under commercials licenses such as Diffrac.Suite TOPAS,