The phase problem

Given recent advances in phasing methods, those new to protein crystallography may be forgiven for asking 'what problem?'. As many of those attending the CCP4 meeting come from a biological background, struggling with expression and crystallization, this introductory paper aims to introduce some of the basics that will hopefully make the subsequent papers penetrable. What is the 'phase' in crystallography? What is 'the problem'? How can we overcome the problem? The paper will emphasize that the phase values can only be discovered through some prior knowledge of the structure. The paper will canter through direct methods, isomorphous replacement, anomalous scattering and molecular replacement. As phasing is the most acronymic realm of crystallography, MR, SIR, SIRAS, MIR, MIRAS, MAD and SAD will be expanded and explained in part. Along the way, we will meet some of the heroes of protein crystallography such as Perutz, Kendrew, Crick, Rossmann and Blow who established many of the phasing methods in the UK. It is inevitable that some basic mathematics is encountered, but this will be done as gently as possible.