Macromolecule crystal structure analyses can be severely hampered by cases of twinning or of lattice disorders or of multiple crystals. However, it is increasingly the case that twinning can readily be recognized and accounted for, or remediations found. A review of this topic is given, covering both the less-than-perfect and perfect twinning situations. Remediation of twinning cases is possible via alteration of crystal growth conditions including use, mainly, of chemical additives. The case of multiple crystal growths likewise can hamper crystal structure analysis and, although not necessarily associated with twinning, is a crystal growth situation where similar remediation methods are adopted. There is a nice body of case studies now in the crystallographic literature about macromolecule crystal twinning and multiple crystals situations that make it timely to write this review. The literature on other macromolecule crystal disorders is much smaller but include incommensurate superlattice effects, which are also described. This review concludes with a personal view of the future possible directions. There are new avenues to deal with multiple crystal cases using physical crystallography approaches, such as sample sprays for freezing macromolecule microcrystallites and femtosecond lasers for exactly cutting out crystal fragments. There is a considerable potential for molecular replacement to provide an efficient way for using twinned X-ray data, at least where there is a high amino acid sequence identity, and as ‘protein fold space’ coverage becomes much more complete. 1The terms ‘Macromolecular’ and ‘Macromolecular Crystallography’ sometimes abbreviated ‘MX’, refer to crystals of protein-nucleic acid (DNA or RNA) complexes and/or DNA crystals as well as ‘simply proteins on their own’.
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