Better structures from better data through better methods:: a review of developments in de novo macromolecular phasing techniques and associated instrumentation at LURE

This paper presents a survey of developments in de novo phasing methods and instrumentation in protein crystallography that have been carried out over the past 20 years at the French synchrotron radiation facility LURE. This includes progress in detector technology, particularly with multiwire proportional chambers, contributions to the development of the MAD and MASC methods for experimental phase-determination via anomalous dispersion, the exploration of the use of xenon and krypton as heavy atoms and anomalous scatterers, as well as the substantialization of parts of the 'Bayesian programme' for structure determination in highly efficient and user-friendly software. It is shown how the conjunction of high-quality data collection with novel phasing methods and with optimized data-processing schemes can bring about major improvements, even when the signal is very weak, in the accuracy of structural determinations.