Ab initio phasing using diffraction data from different crystal forms

The crystallographic phase problem is routinely solved when imaging small molecules but remains a key component and difficult step in protein crystallography. Current phasing approaches are either experimentally based or rely on the knowledge of an homologous structure. With the recent advances in phasing algorithms called iterative projections algorithms (IPAs), ab initio phasing methods, where only minimal extra information is needed are gaining interest in protein crystallography, as they potentially offer a dramatic reduction in effort over experimental methods and are not affected by model bias. Two versions of a new ab initio phase retrieval method are presented in this paper. These rely on the measurement of the diffraction from two or more crystal forms of the same molecule. The required IPA constraint projections are derived and 2D simulations using the difference map algorithm to illustrate the convergence properties of the methods in presence of object overlap. A 3D simulation illustrates potential use and effectiveness of the algorithm.