Results on the Application of Direct Methods to Protein Crystallgraphy and Electron Microscopy

Abstract

Multiple isomorphousreplacement is now dominating the structure analysis of proteins with no structural precedent. It may occur that the derivatives are not isomorphous with the native protein. In this case multi-wavelength anomalous scattering (MAS) can in principle be used, if there are some suitable heavy atoms in the native protein or its non-isomorphous derivative. However MAS technique suffers from the difficulty of collecting and scaling data at different wavelengths accurately. OAS technique does not have this difficulty but it leads to the problem of phase ambiguity. A direct method has been proposed to solve this problem [Fan et al. (1984). Acta Cry st. A40, 489–495; 495–498.]. The method has been tested with the Hg-derivative of a known protein, avian pancreatic polypeptide [Glover et al. (1985). Adv. Biophys. 20, 1–12.]. It resulted in an interpretable Fourier map. A part of which together with the true structure model is shown in Fig. 1.