PHASING METHODS FOR PROTEIN CRYSTALLOGRAPHY

The phase problem has been formulated as one of constrained global min imization and it leads to the minimal principle, which is the theoreti cal basis of 'Shake-and-Bake'-an algorithm for the automatic solution of the phase problem, ab initio, A related approach (termed 'Half-Bake d') that, as in Shake-and-Bake, alternates phase refinement in recipro cal space with density modification in real space, has recently been f ormulated. The traditional techniques of direct methods have been inte grated with isomorphous replacement and anomalous scattering and the f irst applications have been made, The accurate measurement of a limite d number of structure invariants by means of multiple beam X-ray diffr action has become a reality. A feasibility study shows that, in combin ation with the direct method, the ability to measure the values of the structure invariants experimentally will strengthen existing techniqu es. (C) Current Biology Ltd ISSN 0959-440X