In principle, the availability of high-resolution micrographs in electron crystallography is a direct solution of the phase problem that has been used to great advantage for the study of proteins. However, as the resolution of the determination increases, the Fourier transform of the micrograph becomes a less accurate phase source. Hence, alternative direct methods for phase determination have been evaluated, if only to extend the resolution of most reliable lower resolution phases to the limit of the electron diffraction pattern. The first demonstration of its feasibility was published in a study of bacteriorhodopsin extending 15 Å image phases to beyond 3 Å by maximum entropy and likelihood procedures i. Later studies demonstrated that convolutional methods also can be effective.
In protein crystallography, there is always an interest in carrying out a true ab initio determinations, if only because of the challenge to traditional direct methods that become statistically less reliable as the number of atoms in the unit cell increases.