It’s all in the crystals…

Macromolecular crystallography relies on the availability and quality of single crystals; these are typically obtained through extensive screening, which has a very low intrinsic success rate. Crystallization is not a completely stochastic process and many proteins do not succumb to crystallization because of specific microscopic features of their molecular surfaces. It follows that rational surface engineering through site-directed mutagenesis should allow a systematic and significant improvement in crystallization success rates. Here, one such established strategy, surface-entropy reduction (SER), is discussed, including its successes, limitations and possible future developments.