The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disorderedZ′ = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures.

The size and complexity of molecules being studied by single crystal diffraction is growing year by year, resulting in an increase in the difficulties encountered during structure determination. From the crystallisation itself and sample handling, to structure solution and refinement, specific problems due to larger molecules are discussed. During refinement, several methods are available to deal with the problems encountered with large structures within the software Crystals. Hydrogens atoms can neither be found easily nor refined freely, but restraints can be applied automatically. Special scattering factors can be used to model complex disorder. Finally chemical information can be included in the form of restraints in order to help the determination of a good model. Multicollinearity problems are more likely in the refinement of large structures; to some extent more precise and accurate algorithms can help. Also, if the global minimum is less well defined, faster refinement enables more cycles to be carried out, a necessity for good convergence. The efficiency of the algorithms in Crystals have been increased to help address these issues. Thus, crystal structures are getting larger and their complexity is increasing. Recent developments in precision and speed during the least squares in Crystals is helping the structural scientist to deal with larger structures more efficiently.