Image definition evaluation functions for X-ray crystallography: a new perspective on the phase problem

Abstract

The core theme of X-ray crystallography is reconstructing the electron-density distribution of crystals under the constraints of observed diffraction data. Nevertheless, reconstruction of the electron-density distribution by straightforward Fourier synthesis is usually hindered due to the well known phase problem and the finite resolution of diffraction data. In analogy with optical imaging systems, the reconstructed electron-density map may be regarded as the image of the real electron-density distribution in crystals. Inspired by image definition evaluation functions applied in the auto-focusing process, two evaluation functions are proposed for the reconstructed electron-density images. One of them is based on the atomicity of the electron-density distribution and properties of Fourier synthesis. Tests were performed on synthetic data of known structures, and it was found that this evaluation function can distinguish the correctly reconstructed electron-density image from wrong ones when diffraction data of atomic resolution are available. An algorithm was established based on this evaluation function and applied in reconstructing the electron-density image from the synthetic data of known structures. The other evaluation function, which is based on the positivity of electron density and constrained power spectrum entropy maximization, was designed for cases where only diffraction data of rather limited resolution are available. Tests on the synthetic data indicate that this evaluation function may identify the correct phase set even for a data set with resolution as low as 3.5 Å. Though no algorithm for structure solution has been figured out based on the latter function, the results presented here provide a new perspective on the phase problem.