Direct methods beyond small‐molecule crystallography

Abstract

The development of direct methods outside their traditional field began since the middle 1960s. New applications were explored gradually in four directions. They are the transition of: (i) from single crystals to powder samples, (ii) from X‐ray crystallography to electron microscopy (EM), (iii) from periodic structures to incommensurate structures and (iv) from small molecules to macromolecular structures. The research on methods of solving crystal structures at the Institute of Physics in Beijing has been focused on the last three directions. The transition of direct methods from X‐ray crystallography to EM led to a two‐step image processing technique in high‐resolution electron microscopy (HREM). This technique combines information of EM and that of electron diffraction (ED) revealing the structure of minute crystals that are unsuitable for X‐ray diffraction analysis. The transition of direct methods from periodic crystal structures to incommensurate structures led to the multi‐dimensional direct methods enabling ab initio solution of incommensurate modulated structures and composite structures without relying on an assumed modulation model or even the known basic structure. Finally the combination of direct methods with traditional protein crystallographic methods has greatly enhanced the ability of solving protein structures.